Combination Chemotherapy With or Without Blinatumomab in Treating Patients With Newly Diagnosed BCR-ABL-Negative B Lineage Acute Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

A Phase III Randomized Trial of Blinatumomab for Newly Diagnosed BCR-ABL-Negative B Lineage Acute Lymphoblastic Leukemia in Adults

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02003222
• Other study ID #: NCI-2013-02229
• Secondary ID: NCI-2013-02229EC
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: May 19, 2014
• Est. completion date: December 4, 2024

Study information

• Verified date: December 2023
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase III trial studies combination chemotherapy with blinatumomab to see how well it works compared to induction chemotherapy alone in treating patients with newly diagnosed breakpoint cluster region (BCR)-c-abl oncogene 1, non-receptor tyrosine kinase (ABL)-negative B lineage acute lymphoblastic leukemia. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as blinatumomab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether combination chemotherapy is more effective with or without blinatumomab in treating newly diagnosed acute lymphoblastic leukemia.

Description:

PRIMARY OBJECTIVE:

I. To compare the overall survival (OS) of blinatumomab in conjunction with chemotherapy to chemotherapy alone in patients with BCR-ABL-negative B cell precursor acute lymphoblastic leukemia (ALL) who are minimal residual disease (MRD) negative after induction and intensification chemotherapy, based on multiparameter flow cytometric (MFC) assessment of residual blasts.

SECONDARY OBJECTIVES:

I. To compare the relapse-free survival (RFS) of blinatumomab in conjunction with chemotherapy to chemotherapy alone in MRD negative patients after induction and intensification chemotherapy.

II. To compare the OS and RFS of those patients who are MRD positive (+) at step 3 randomization/registration and then convert to MRD negative (-) after 2 cycles of blinatumomab to those patients who are MRD- at randomization and remain MRD- after 2 cycles of blinatumomab or consolidation chemotherapy.

III. To assess the toxicities of blinatumomab in this patient population. IV. To assess the toxicities of the modified E2993 chemotherapy regimen in this patient population.

V. To describe the outcome of patients who proceed to allogeneic blood or marrow transplant after treatment with or without blinatumomab.

LABORATORY OBJECTIVES:

I. To determine differences in MRD kinetics among patients with the BCR/ABL1-like B-lineage ALL, and to compare the OS (and RFS) of patients with BCR-ABL-like phenotype with those without BCR-ABL-like phenotype.

II. To evaluate the incidence of anti-blinatumomab antibody formation.

OUTLINE:

INDUCTION CHEMOTHERAPY: Patients receive cytarabine intrathecally (IT) on day 1; daunorubicin hydrochloride intravenously (IV) over 10-15 minutes on days 1, 8, 15, and 22; vincristine sulfate IV on days 1, 8, 15, and 22; dexamethasone orally (PO) daily on days 1-7 (and 15-21 for patients age < 55 years only); methotrexate IT on day 14; pegaspargase intramuscularly (IM) or IV on day 18 (patients age < 55 years); and CD20 positive patients may optionally receive rituximab IV on day 8 and 15. Beginning on day 29, patients with absolute neutrophil count (ANC) >= 0.75 x 10^9/L and platelets > 75 x 10^9/L (patients with delayed hematologic recovery) (patients with residual disease that is delaying count begin treatment immediately) receive cyclophosphamide IV over 30 minutes on days 1 and 29, cytarabine IV over 30 minutes or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39, mercaptopurine PO on days 1-14, 29-42, pegaspargase IM or IV on day 15 (patients age < 55 years), patients receiving treatment for central nervous system (CNS) 2 or 3 leukemia in cycle 1 receive methotrexate IT on days 1, 8, 15, and 22, and CD20 positive patients may optionally receive rituximab IV on days 8 and 15.

INTENSIFICATION THERAPY: Beginning 4 weeks after the completion of cycle 2 of induction therapy, patients receive intensification therapy comprising high-dose methotrexate IV over 2 hours on days 1 and 8, and pegaspargase IM or IV on day 9.

Patients are then randomized to 1 of 2 treatment arms.

Patients randomized to the blinatumomab group receive blinatumomab IV continuously on days 1-28. Treatment repeats every 6 weeks for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients may then undergo allogeneic stem cell transplant (SCT) or proceed to consolidation therapy per investigator discretion.

CONSOLIDATION THERAPY: Beginning after the second cycle of blinatumomab (patients randomized to the blinatumomab group) or after intensification therapy (patients not randomized to blinatumomab), patients receive cytarabine IV over 30 minutes or SC on days 1-5, etoposide IV over 1 hour on days 1-5, methotrexate IT on day 1, and pegaspargase IM or IV on day 5, and CD20 positive patients may optionally receive rituximab IV on day 5. Beginning 4 weeks from day 1 of cycle 1, patients receive cytarabine, etoposide, methotrexate, and CD20 positive patients may receive rituximab as in cycle 1. Beginning 4 weeks from day 1 of cycle 2, patients receive daunorubicin hydrochloride IV over 10-15 minutes on day 1, 8, 15, and 22; vincristine sulfate IV on days 1, 8, 15, and 22; dexamethasone PO daily on days 1-7 (and 15-21 for patients age < 55 years); methotrexate IT on day 2; cyclophosphamide IV over 30 minutes on day 29; cytarabine IV over 30 minutes or SC on days 30-33 and 37-40; mercaptopurine PO on days 29-42 and CD20 positive patients may receive rituximab on day 8. Beginning 8 weeks from day 1 of cycle 3, patients receive cytarabine, etoposide, methotrexate, and CD20 positive patients may optionally receive rituximab as in cycle 1. Patients randomized to blinatumomab repeat cycle 4 and then receive blinatumomab IV continuously on days 1-28.

MAINTENANCE THERAPY: Within 6 weeks after beginning last cycle of consolidation therapy, patients receive mercaptopurine PO daily, methotrexate PO or IV over 2 hours once weekly for 2.5 years, vincristine sulfate IV on day 1 every 3 months, prednisone PO on days 1-5 every 3 months, and methotrexate IT on day 1 every 3 months. Treatment continues for up to 2.5 years in the absence of disease progression or unacceptable toxicity.

Patients undergo x-ray imaging during screening, lumbar puncture while on study, and bone marrow aspiration, bone marrow biopsy, and blood sample collection throughout the study.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then every 12 months for 5 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 488
• Est. completion date: December 4, 2024
• Est. primary completion date: June 23, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 30 Years to 70 Years

Eligibility

Inclusion Criteria:

• PRE-REGISTRATION

• Diagnostic bone marrow and peripheral blood specimens must be submitted for immunophenotyping and selected molecular testing, and the establishment of BCR/ABL status; testing will be performed by the Eastern Cooperative Oncology Group (ECOG)-American College of Radiation Imaging Network (ACRIN) Leukemia Translational Research Laboratory (LTRL) and reported to the institution

• NOTE: IT IS ESSENTIAL THAT A SAMPLE CONTAINING SUFFICIENT BLAST CELLS BE SUBMITTED TO THE ECOG-ACRIN LTRL AT BASELINE SO THAT SUBSEQUENT BONE MARROW ASSESSMENTS OF MRD CAN BE DONE; IN ADDITION TO ALLOWING THE LTRL TO CONFIRM ELIGIBILITY BASED ON BLAST CELL IMMUNOPHENOTYPE AND BCR/ABL STATUS, IT IS ALSO IMPERATIVE THAT AN ADEQUATE NUMBER OF BLASTS BE BANKED FOR ANALYSIS BY DRS MULLIGHAN/WILLMAN. WITHOUT ADEQUATE BASELINE SAMPLES, PATIENTS WILL NOT BE ABLE TO BE TREATED AND RANDOMIZED ON THIS PROTOCOL; IF A BONE MARROW ASPIRATE IS NOT AVAILABLE FOR LTRL SUBMISSION AT BASELINE, IT IS IMPERATIVE THAT DR PAIETTA FROM THE LTRL IS CALLED TO DISCUSS THE PERIPHERAL BLOOD WBC AND BLAST COUNT BEFORE BLOOD ONLY IS SUBMITTED

• NOTE: Hydroxyurea can be given for up to 5 days prior to initiation of protocol therapy for control of leukocyte count and/or other symptoms or signs; corticosteroids can be given after pre-registration to the protocol and submission of baseline marrow and blood samples for control of leukocyte count and/or other symptoms or signs prior to initiation of protocol therapy if needed; if corticosteroids are given prior to pre-registration, contact the study chair as the patient may still be eligible to participate

• INDUCTION ELIGIBILITY CRITERIA-STEP 1

• Age >= 30 years and =< 70 years

• New diagnosis of B lineage ALL must be made upon bone marrow or peripheral blood immunophenotyping; cases with myeloid antigen expression, but unequivocal lymphoid immunophenotype, are eligible

• Negativity for the Philadelphia chromosome must be established by conventional cytogenetics, fluorescence in situ hybridization (FISH) and/or polymerase chain reaction (PCR); patients who are negative for the Philadelphia chromosome by conventional cytogenetics must have FISH or PCR performed for BCR/ABL to exclude occult translocations

• Cytogenetic analysis must be performed from diagnostic bone marrow (preferred) or if adequate number of circulating blasts from peripheral blood; FISH testing for common B-lineage ALL abnormalities including t(9;22) (BCR/ABL1), t(12;21) (ETS-variant gene 6 [ETV6]/runt-related transcription factor 1 [RUNX1]), t(1;19) (pre-B-cell leukemia homeobox 1 [PBX1]/transcription factor 3 [TCF3]), +4,+10,+17, (centromeric [Cen]4/Cen10/Cen17), t(11q23;var), (myeloid/lymphoid or mixed lineage leukemia [MLL]), deletion (del)(9p) (cyclin-dependent kinase inhibitor 2A [CDKN2A]/Cen9), and t(14;var) (immunoglobulin heavy chain [IGH] is encouraged); if there are few or no circulating blasts and an adequate marrow sample cannot be obtained for cytogenetic analysis, the patient may still enroll on the trial

• Serum direct bilirubin < 2 mg/dl or serum total bilirubin =< 3 (obtained =< 48 hours prior to registration); NOTE: the above stipulation for normal hepatic function does not apply if liver dysfunction is due to leukemia infiltration

• Serum creatinine < 2 mg/dl (obtained =< 48 hours prior to registration); NOTE: the above stipulation for normal hepatic function does not apply if liver dysfunction is due to leukemia infiltration

• Patient should be human leukocyte antigen (HLA) typed (A, B, C, DR and DQ) during induction therapy phase or a written explanation for not undergoing HLA typing on the flow sheet

• Patients with known human immunodeficiency virus (HIV) infection are eligible if they meet all of the following criteria:

• No history of acquired immune deficiency syndrome (AIDS)-related complications other than a history of low CD4+ T-cell count (< 200/mm^3) prior to initiation of combination antiretroviral therapy; on study CD4+ T-cell count may not be informative due to leukemia and should not be used as an exclusion criterion if low

• Patient must be healthy on the basis of HIV disease with high likelihood of near normal life span were it not for the leukemia

• Patient must have serum HIV viral load of < 200 copies/mm^3

• Patient must be on combination antiretroviral therapy with minimal pharmacokinetic interactions with study therapy and minimal overlapping clinical toxicity with protocol therapy

• Patient must not be receiving protease inhibitors or once daily formulations containing cobicistat, stavudine, or on regimens containing stavudine or zidovudine

• It is recommended to utilize a regimen of the integrase inhibitor, dolutegravir, combined with either disoproxil fumarate/emtricitabine or dolutegravir combined with tenofovir alafenamide/emtricitabine

• Patient must have no history of recent myocardial infarction (within three months), uncontrolled congestive heart failure, or uncontrolled cardiac arrhythmia

• Patient must have a normal cardiac ejection fraction by pretreatment multigated acquisition scan (MUGA) or echocardiogram within 4 weeks prior to registration (resting ejection fraction >= 40% or >= 5% increase with exercise), shortening fraction by echocardiogram >= 24%, or to within the normal range of values for the institution

• Women must not be pregnant or breast-feeding due to administration of teratogenic chemotherapy and must not become pregnant or breastfeed during protocol therapy and for at least 3 months after protocol therapy; woman of childbearing potential must abstain from sexual activity or be willing to use 2 highly effective forms of contraception throughout protocol therapy and for at least an additional 3 months after the last dose of protocol-specified therapy; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)

• Men who have a female partner of childbearing potential must be willing to use 2 highly effective forms of contraception throughout protocol therapy and for at least an additional 3 months after the last dose of protocol-specified therapy; men who have a pregnant partner must be willing to use a condom during sexual activity throughout protocol therapy and for 3 months after the last dose of protocol-specified therapy

• ECOG performance score 0-3

• Patient must have given written informed consent

• POST-INDUCTION THERAPY ELIGIBILITY CRITERIA (PRIOR TO INTENSIFICATION-STEP 2)

• ECOG performance status 0-2

• Patients must have achieved a CR or CRi

• Patients who have achieved a CR or CRi must have maintained peripheral blood evidence of a CR or CRi

• Patient must be CNS (cerebrospinal fluid [CSF]) negative for leukemia

• Patients must have resolved any serious infectious complications related to induction

• Any significant medical complications related to induction must have resolved

• Serum creatinine =< 2.0 mg/dl (obtained =< 48 hours prior to registration)

• Serum direct bilirubin < 2 mg/dL or serum total bilirubin =< 3 (obtained =< 48 hours prior to registration)

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x upper limit of normal (ULN) (obtained =< 48 hours prior to registration)

• RANDOMIZATION OR ASSIGNMENT TO BLINATUMOMAB OR NO BLINATUMOMAB-STEP 3

• Patients must have an ECOG performance status of 0-2

• Patients must have maintained peripheral blood evidence of a remission and must have a CR or CRi, confirmed on restaging bone marrow (BM) aspirate and biopsy

• Patients must have resolved any serious infectious complications related to therapy

• Any significant medical complications related to therapy must have resolved

• Direct or total bilirubin < 1.5 x ULN (unless related to Gilbert's or Meulengracht's syndrome); the values must be obtained within 48 hours prior to randomization

• Serum creatinine < 1.5 x ULN; the values must be obtained within 48 hours prior to randomization

• Bone marrow aspirates must be submitted for centralized minimal residual disease (MRD) assessment performed by the ECOG-ACRIN Leukemia Translational Research Laboratory

• MRD results will be reported to the submitting institution

• NOTE: FOR MRD ASSESSMENTS, AN ASPIRATE FROM A SEPARATE BONE MARROW ASPIRATION SITE MUST BE SUBMITTED (THE NEEDLE CAN BE RE-DIRECTED THROUGH THE SAME SKIN PUNCTURE SITE); ONLY SUBMIT ASPIRATES FROM THE FIRST PULL OF AN ASPIRATION SITE FOR MRD TESTING; DO NOT SUBMIT SAMPLES FROM THE SECOND OR THIRD PULL OF THE SAME ASPIRATION SITE

• In B-lineage ALL, MRD levels in peripheral blood or from a dilute marrow aspiration can be 300% lower, on average, than those in bone marrow at a given time point; submitting a first pull from a separate aspiration site will ensure that MRD determinations used in randomization and trial interpretation are accurate

• NOTE: failure to submit bone marrow aspirates will result in a major violation at the time of an audit

• CRITERIA FOR ALLOGENEIC TRANSPLANTATION

• A suitable donor must be identified; there are no restrictions on donor type and can include a matched sibling, a matched or mismatched unrelated donor, a family haplotype matched donor or a cord blood donor (single or double)

• Patients should meet the eligibility criteria for RANDOMIZATION OR ASSIGNMENT TO BLINATUMOMAB OR NO BLINATUMOMAB-STEP 3

• Patients must be considered reliable enough to comply with the medication regimen and follow-up, and have social support necessary to allow this compliance

• CRITERIA FOR MAINTENANCE THERAPY-STEP 4: Patients must have an ECOG performance status of 0-3

• CRITERIA FOR MAINTENANCE THERAPY-STEP 4: Patients must have maintained peripheral blood evidence of a remission and must have a CR or CRi, confirmed on restaging BM aspirate and biopsy

• CRITERIA FOR MAINTENANCE THERAPY-STEP 4: Patients must have resolved any serious infectious complications related to therapy

• CRITERIA FOR MAINTENANCE THERAPY-STEP 4: Any significant medical complications related to therapy must have resolved

Exclusion Criteria:

• Mature B ALL (Burkitt's-like leukemia) is excluded from enrollment in this trial; pre-study bone marrow biopsy and aspirate must be completed =< 1 week prior to registration

• Patient must not have a concurrent active malignancy for which they are receiving treatment

• Patient must not have intercurrent organ damage or medical problems that will jeopardize the outcome of therapy (i.e., psychiatric disorder, drug abuse, pregnancy)

• Patient must not have an antecedent hematologic disorder

• Patient must not have a history or presence of clinically relevant central nervous system (CNS) pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia; Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis, or other significant CNS abnormalities

• Patient must not have an active uncontrolled infection

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative
• Leukemia
• Leukemia, Lymphoid
• Philadelphia Chromosome
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Procedure:
• Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic hematopoietic SCT
• Biospecimen Collection
Undergo blood sample collection

Biological:
• Blinatumomab
Given IV

Procedure:
• Bone Marrow Aspiration
Undergo bone marrow aspiration
• Bone Marrow Biopsy
Undergo bone marrow biopsy

Drug:
• Cyclophosphamide
Given IV
• Cytarabine
Given IT, IV, or SC
• Daunorubicin
Given IV
• Daunorubicin Hydrochloride
Given IV
• Dexamethasone
Given PO
• Etoposide
Given IV

Procedure:
• Lumbar Puncture
Undergo lumbar puncture

Drug:
• Mercaptopurine
Given PO
• Methotrexate
Given PO, IT or IV
• Pegaspargase
Given IM or IV
• Prednisone
Given PO

Biological:
• Rituximab
Given IV

Drug:
• Vincristine
Given IV
• Vincristine Sulfate
Given IV

Procedure:
• X-Ray Imaging
Undergo x-ray imaging

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	QEII Health Sciences Centre/Nova Scotia Health Authority	Halifax	Nova Scotia
Canada	Kingston Health Sciences Centre	Kingston	Ontario
Canada	CIUSSSEMTL-Hopital Maisonneuve-Rosemont	Montreal	Quebec
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Clinical Research Unit at Vancouver Coastal Health Authority	Vancouver	British Columbia
Israel	Rambam Medical Center	Haifa
Israel	Shaare Zedek Medical Center	Jerusalem
Puerto Rico	Cancer Center-Metro Medical Center Bayamon	Bayamon
Puerto Rico	Doctors Cancer Center	Manati
Puerto Rico	Centro Comprensivo de Cancer de UPR	San Juan
Puerto Rico	San Juan City Hospital	San Juan
Puerto Rico	San Juan Community Oncology Group	San Juan
United States	Providence Regional Cancer System-Aberdeen	Aberdeen	Washington
United States	Bixby Medical Center	Adrian	Michigan
United States	Hickman Cancer Center	Adrian	Michigan
United States	American Fork Hospital / Huntsman Intermountain Cancer Center	American Fork	Utah
United States	Mary Greeley Medical Center	Ames	Iowa
United States	McFarland Clinic - Ames	Ames	Iowa
United States	Community Hospital of Anaconda	Anaconda	Montana
United States	Cancer Care Center at Island Hospital	Anacortes	Washington
United States	Alaska Breast Care and Surgery LLC	Anchorage	Alaska
United States	Alaska Oncology and Hematology LLC	Anchorage	Alaska
United States	Alaska Regional Hospital	Anchorage	Alaska
United States	Alaska Women's Cancer Care	Anchorage	Alaska
United States	Anchorage Associates in Radiation Medicine	Anchorage	Alaska
United States	Anchorage Oncology Centre	Anchorage	Alaska
United States	Anchorage Radiation Therapy Center	Anchorage	Alaska
United States	Katmai Oncology Group	Anchorage	Alaska
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	AnMed Health Cancer Center	Anderson	South Carolina
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	PCR Oncology	Arroyo Grande	California
United States	AdventHealth Infusion Center Asheville	Asheville	North Carolina
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Northside Hospital	Atlanta	Georgia
United States	MultiCare Auburn Medical Center	Auburn	Washington
United States	Rocky Mountain Cancer Centers-Aurora	Aurora	Colorado
United States	The Medical Center of Aurora	Aurora	Colorado
United States	Saint Alphonsus Medical Center-Baker City	Baker City	Oregon
United States	Saint Louis Cancer and Breast Institute-Ballwin	Ballwin	Missouri
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey
United States	Medical Center of Baton Rouge	Baton Rouge	Louisiana
United States	Ochsner Health Center-Summa	Baton Rouge	Louisiana
United States	Ochsner High Grove	Baton Rouge	Louisiana
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	Indu and Raj Soin Medical Center	Beavercreek	Ohio
United States	Nebraska Medicine-Bellevue	Bellevue	Nebraska
United States	Overlake Medical Center	Bellevue	Washington
United States	Swedish Cancer Institute-Eastside Oncology Hematology	Bellevue	Washington
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Saint Charles Health System	Bend	Oregon
United States	Walter Reed National Military Medical Center	Bethesda	Maryland
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Saint Vincent Frontier Cancer Center	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Joseph Medical Center	Bloomington	Illinois
United States	Saint Elizabeth Boardman Hospital	Boardman	Ohio
United States	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	Central Care Cancer Center - Bolivar	Bolivar	Missouri
United States	Parkland Health Center-Bonne Terre	Bonne Terre	Missouri
United States	McFarland Clinic - Boone	Boone	Iowa
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Boulder Community Hospital	Boulder	Colorado
United States	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado
United States	Toledo Clinic Cancer Centers-Bowling Green	Bowling Green	Ohio
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Cox Cancer Center Branson	Branson	Missouri
United States	Lafayette Family Cancer Center-EMMC	Brewer	Maine
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Montefiore Medical Center-Einstein Campus	Bronx	New York
United States	Montefiore Medical Center-Weiler Hospital	Bronx	New York
United States	Henry Ford Cancer Institute-Downriver	Brownstown	Michigan
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Memorial Hospital of Carbondale	Carbondale	Illinois
United States	Carson Tahoe Regional Medical Center	Carson City	Nevada
United States	SIH Cancer Institute	Carterville	Illinois
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Rocky Mountain Oncology	Casper	Wyoming
United States	Sandra L Maxwell Cancer Center	Cedar City	Utah
United States	Dayton Physicians LLC-Miami Valley South	Centerville	Ohio
United States	Miami Valley Hospital South	Centerville	Ohio
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Providence Regional Cancer System-Centralia	Centralia	Washington
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Cheyenne Regional Medical Center-West	Cheyenne	Wyoming
United States	Mount Sinai Hospital Medical Center	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Oncology Hematology Care Inc-Anderson	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Blue Ash	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Eden Park	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Kenwood	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Mercy West	Cincinnati	Ohio
United States	University of Cincinnati Cancer Center-UC Medical Center	Cincinnati	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Henry Ford Macomb Hospital-Clinton Township	Clinton Township	Michigan
United States	Community Cancer Institute	Clovis	California
United States	University Oncology Associates	Clovis	California
United States	AdventHealth Infusion Center Haywood	Clyde	North Carolina
United States	Big Horn Basin Cancer Center	Cody	Wyoming
United States	Billings Clinic-Cody	Cody	Wyoming
United States	Kootenai Health - Coeur d'Alene	Coeur d'Alene	Idaho
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Memorial Sloan Kettering Commack	Commack	New York
United States	Bay Area Hospital	Coos Bay	Oregon
United States	UM Sylvester Comprehensive Cancer Center at Coral Springs	Coral Springs	Florida
United States	Oncology Hematology Care Inc-Crestview	Crestview Hills	Kentucky
United States	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri
United States	Parkland Memorial Hospital	Dallas	Texas
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Dayton Physician LLC-Miami Valley Hospital North	Dayton	Ohio
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Miami Valley Hospital North	Dayton	Ohio
United States	Beaumont Hospital - Dearborn	Dearborn	Michigan
United States	Henry Ford Medical Center-Fairlane	Dearborn	Michigan
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	UM Sylvester Comprehensive Cancer Center at Deerfield Beach	Deerfield Beach	Florida
United States	Cancer Center of Colorado at Sloan's Lake	Denver	Colorado
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	National Jewish Health-Main Campus	Denver	Colorado
United States	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado
United States	Rocky Mountain Cancer Centers-Midtown	Denver	Colorado
United States	Rocky Mountain Cancer Centers-Rose	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	SCL Health Saint Joseph Hospital	Denver	Colorado
United States	The Women's Imaging Center	Denver	Colorado
United States	Western Surgical Care	Denver	Colorado
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Illinois CancerCare-Dixon	Dixon	Illinois
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	Prisma Health Cancer Institute - Easley	Easley	South Carolina
United States	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Swedish Cancer Institute-Edmonds	Edmonds	Washington
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Walter Knox Memorial Hospital	Emmett	Idaho
United States	Mountain Blue Cancer Care Center - Swedish	Englewood	Colorado
United States	Swedish Medical Center	Englewood	Colorado
United States	Green Bay Oncology - Escanaba	Escanaba	Michigan
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	Fairbanks Memorial Hospital	Fairbanks	Alaska
United States	Oncology Hematology Care Inc-Healthplex	Fairfield	Ohio
United States	Farmington Health Center	Farmington	Utah
United States	Parkland Health Center - Farmington	Farmington	Missouri
United States	Beaumont Hospital - Farmington Hills	Farmington Hills	Michigan
United States	Weisberg Cancer Treatment Center	Farmington Hills	Michigan
United States	Armes Family Cancer Center	Findlay	Ohio
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Orion Cancer Care	Findlay	Ohio
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	McFarland Clinic - Trinity Cancer Center	Fort Dodge	Iowa
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Mercy Hospital Fort Smith	Fort Smith	Arkansas
United States	Parkview Hospital Randallia	Fort Wayne	Indiana
United States	Parkview Regional Medical Center	Fort Wayne	Indiana
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Dayton Physicians LLC-Atrium	Franklin	Ohio
United States	Vanderbilt-Ingram Cancer Center Cool Springs	Franklin	Tennessee
United States	Fredericksburg Oncology Inc	Fredericksburg	Virginia
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
United States	Gibbs Cancer Center-Gaffney	Gaffney	South Carolina
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Western Illinois Cancer Treatment Center	Galesburg	Illinois
United States	Central Care Cancer Center - Garden City	Garden City	Kansas
United States	MultiCare Gig Harbor Medical Park	Gig Harbor	Washington
United States	NorthShore University HealthSystem-Glenbrook Hospital	Glenview	Illinois
United States	National Jewish Health-Western Hematology Oncology	Golden	Colorado
United States	Grand Valley Oncology	Grand Junction	Colorado
United States	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado
United States	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Trinity Health Grand Rapids Hospital	Grand Rapids	Michigan
United States	Central Care Cancer Center - Great Bend	Great Bend	Kansas
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	North Colorado Medical Center	Greeley	Colorado
United States	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin
United States	Dayton Physicians LLC-Wayne	Greenville	Ohio
United States	Greenville Health System Cancer Institute-Andrews	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Faris	Greenville	South Carolina
United States	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina
United States	Saint Francis Cancer Center	Greenville	South Carolina
United States	Saint Francis Hospital	Greenville	South Carolina
United States	Wayne Hospital	Greenville	Ohio
United States	Gibbs Cancer Center-Pelham	Greer	South Carolina
United States	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	William Beaumont Hospital-Grosse Pointe	Grosse Pointe	Michigan
United States	Memorial Sloan Kettering Westchester	Harrison	New York
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	Saint Peter's Community Hospital	Helena	Montana
United States	Cancer and Blood Specialists-Henderson	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada - Henderson	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada-Horizon Ridge	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada-Southeast Henderson	Henderson	Nevada
United States	GenesisCare USA - Henderson	Henderson	Nevada
United States	Las Vegas Cancer Center-Henderson	Henderson	Nevada
United States	Las Vegas Urology - Green Valley	Henderson	Nevada
United States	Las Vegas Urology - Pebble	Henderson	Nevada
United States	OptumCare Cancer Care at Seven Hills	Henderson	Nevada
United States	Urology Specialists of Nevada - Green Valley	Henderson	Nevada
United States	AdventHealth Hendersonville	Hendersonville	North Carolina
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	Hematology Oncology Associates of Illinois-Highland Park	Highland Park	Illinois
United States	NorthShore University HealthSystem-Highland Park Hospital	Highland Park	Illinois
United States	UM Sylvester Comprehensive Cancer Center at Hollywood	Hollywood	Florida
United States	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas
United States	Ben Taub General Hospital	Houston	Texas
United States	Houston Methodist Hospital	Houston	Texas
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Centerpoint Medical Center LLC	Independence	Missouri
United States	Franciscan Health Indianapolis	Indianapolis	Indiana
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
United States	Allegiance Health	Jackson	Michigan
United States	Baptist MD Anderson Cancer Center	Jacksonville	Florida
United States	McFarland Clinic - Jefferson	Jefferson	Iowa
United States	Capital Region Southwest Campus	Jefferson City	Missouri
United States	Freeman Health System	Joplin	Missouri
United States	Mercy Hospital Joplin	Joplin	Missouri
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Presence Saint Mary's Hospital	Kankakee	Illinois
United States	Heartland Hematology and Oncology Associates Incorporated	Kansas City	Missouri
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	First Dayton Cancer Care	Kettering	Ohio
United States	Greater Dayton Cancer Center	Kettering	Ohio
United States	Kettering Medical Center	Kettering	Ohio
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Cancer Center of Kansas-Kingman	Kingman	Kansas
United States	Kingman Regional Medical Center	Kingman	Arizona
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Providence Regional Cancer System-Lacey	Lacey	Washington
United States	Good Samaritan Medical Center	Lafayette	Colorado
United States	Northwell Health/Center for Advanced Medicine	Lake Success	New York
United States	Carolina Blood and Cancer Care Associates PA-Lancaster	Lancaster	South Carolina
United States	Sparrow Hospital	Lansing	Michigan
United States	Alliance for Childhood Diseases/Cure 4 the Kids Foundation	Las Vegas	Nevada
United States	Ann M Wierman MD LTD	Las Vegas	Nevada
United States	Cancer and Blood Specialists-Shadow	Las Vegas	Nevada
United States	Cancer and Blood Specialists-Tenaya	Las Vegas	Nevada
United States	Cancer Therapy and Integrative Medicine	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Northwest	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Town Center	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada-Summerlin	Las Vegas	Nevada
United States	Desert West Surgery	Las Vegas	Nevada
United States	GenesisCare USA - Fort Apache	Las Vegas	Nevada
United States	GenesisCare USA - Las Vegas	Las Vegas	Nevada
United States	GenesisCare USA - Vegas Tenaya	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-San Martin	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Tenaya	Las Vegas	Nevada
United States	Hope Cancer Care of Nevada	Las Vegas	Nevada
United States	Las Vegas Cancer Center-Medical Center	Las Vegas	Nevada
United States	Las Vegas Prostate Cancer Center	Las Vegas	Nevada
United States	Las Vegas Urology - Cathedral Rock	Las Vegas	Nevada
United States	Las Vegas Urology - Pecos	Las Vegas	Nevada
United States	Las Vegas Urology - Smoke Ranch	Las Vegas	Nevada
United States	Las Vegas Urology - Sunset	Las Vegas	Nevada
United States	OptumCare Cancer Care at Charleston	Las Vegas	Nevada
United States	OptumCare Cancer Care at Fort Apache	Las Vegas	Nevada
United States	OptumCare Cancer Care at MountainView	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Southeast	Las Vegas	Nevada
United States	Summerlin Hospital Medical Center	Las Vegas	Nevada
United States	Sunrise Hospital and Medical Center	Las Vegas	Nevada
United States	University Cancer Center	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Urology Specialists of Nevada - Central	Las Vegas	Nevada
United States	Urology Specialists of Nevada - Northwest	Las Vegas	Nevada
United States	Urology Specialists of Nevada - Southwest	Las Vegas	Nevada
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri
United States	Kansas Institute of Medicine Cancer and Blood Center	Lenexa	Kansas
United States	Minimally Invasive Surgery Hospital	Lenexa	Kansas
United States	Cancer Center of Kansas-Liberal	Liberal	Kansas
United States	Liberty Radiation Oncology Center	Liberty	Missouri
United States	AMG Libertyville - Oncology	Libertyville	Illinois
United States	Lima Memorial Hospital	Lima	Ohio
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Rocky Mountain Cancer Centers-Littleton	Littleton	Colorado
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	Logan Regional Hospital	Logan	Utah
United States	Rocky Mountain Cancer Centers-Sky Ridge	Lone Tree	Colorado
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	PeaceHealth Saint John Medical Center	Longview	Washington
United States	The James Graham Brown Cancer Center at University of Louisville	Louisville	Kentucky
United States	McKee Medical Center	Loveland	Colorado
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	North Shore University Hospital	Manhasset	New York
United States	Cancer Center of Kansas-Manhattan	Manhattan	Kansas
United States	Holy Family Memorial Hospital	Manitowoc	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Marinette	Marinette	Wisconsin
United States	McFarland Clinic - Marshalltown	Marshalltown	Iowa
United States	Marshfield Medical Center	Marshfield	Wisconsin
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio
United States	Toledo Radiation Oncology at Northwest Ohio Onocolgy Center	Maumee	Ohio
United States	Loyola University Medical Center	Maywood	Illinois
United States	Cancer Center of Kansas - McPherson	McPherson	Kansas
United States	Idaho Urologic Institute-Meridian	Meridian	Idaho
United States	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	UM Sylvester Comprehensive Cancer Center at Kendall	Miami	Florida
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Dayton Physicians LLC-Signal Point	Middletown	Ohio
United States	Memorial Sloan Kettering Monmouth	Middletown	New Jersey
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Community Medical Hospital	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Mercy Memorial Hospital	Monroe	Michigan
United States	Ochsner LSU Health Monroe Medical Center	Monroe	Louisiana
United States	Toledo Clinic Cancer Centers-Monroe	Monroe	Michigan
United States	Memorial Sloan Kettering Bergen	Montvale	New Jersey
United States	Franciscan Health Mooresville	Mooresville	Indiana
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Intermountain Medical Center	Murray	Utah
United States	Trinity Health Muskegon Hospital	Muskegon	Michigan
United States	Saint Alphonsus Cancer Care Center-Nampa	Nampa	Idaho
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	Vanderbilt Breast Center at One Hundred Oaks	Nashville	Tennessee
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Yale University	New Haven	Connecticut
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	Illinois Cancer Specialists-Niles	Niles	Illinois
United States	Lakeland Hospital Niles	Niles	Michigan
United States	Cancer and Hematology Centers of Western Michigan - Norton Shores	Norton Shores	Michigan
United States	Henry Ford Medical Center-Columbus	Novi	Michigan
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	Saint Vincent Hospital Cancer Center at Oconto Falls	Oconto Falls	Wisconsin
United States	McKay-Dee Hospital Center	Ogden	Utah
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Olathe Health Cancer Center	Olathe	Kansas
United States	Nebraska Medicine-Village Pointe	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Saint Alphonsus Medical Center-Ontario	Ontario	Oregon
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	Saint Charles Hospital	Oregon	Ohio
United States	Toledo Clinic Cancer Centers-Oregon	Oregon	Ohio
United States	Providence Willamette Falls Medical Center	Oregon City	Oregon
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Radiation Oncology of Northern Illinois	Ottawa	Illinois
United States	Menorah Medical Center	Overland Park	Kansas
United States	Saint Luke's South Hospital	Overland Park	Kansas
United States	Hope Cancer Care of Nevada-Pahrump	Pahrump	Nevada
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	OSF Saint Francis Radiation Oncology at Peoria Cancer Center	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Valley Radiation Oncology	Peru	Illinois
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	UM Sylvester Comprehensive Cancer Center at Plantation	Plantation	Florida
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Huron Medical Center PC	Port Huron	Michigan
United States	Lake Huron Medical Center	Port Huron	Michigan
United States	Jefferson Healthcare	Port Townsend	Washington
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho
United States	Cancer Center of Kansas - Pratt	Pratt	Kansas
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Utah Valley Regional Medical Center	Provo	Utah
United States	MultiCare Good Samaritan Hospital	Puyallup	Washington
United States	Saint Charles Health System-Redmond	Redmond	Oregon
United States	Spectrum Health Reed City Hospital	Reed City	Michigan
United States	Radiation Oncology Associates	Reno	Nevada
United States	Renown Regional Medical Center	Reno	Nevada
United States	Saint Mary's Regional Medical Center	Reno	Nevada
United States	Valley Medical Center	Renton	Washington
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	Reid Health	Richmond	Indiana
United States	VCU Massey Cancer Center at Stony Point	Richmond	Virginia
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Riverton Hospital	Riverton	Utah
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	Carolina Blood and Cancer Care Associates PA	Rock Hill	South Carolina
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	Michigan Cancer Specialists	Roseville	Michigan
United States	Cancer Care Associates PC	Royal Oak	Michigan
United States	Comprehensive Medical Center PLLC	Royal Oak	Michigan
United States	Hematology Oncology Consultants PC	Royal Oak	Michigan
United States	Oakland Colon Rectal Associates	Royal Oak	Michigan
United States	Oakland Medical Group	Royal Oak	Michigan
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
United States	Saint George Regional Medical Center	Saint George	Utah
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan
United States	Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Mercy Hospital South	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri
United States	Siteman Cancer Center-South County	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri
United States	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	LDS Hospital	Salt Lake City	Utah
United States	Utah Cancer Specialists-Salt Lake City	Salt Lake City	Utah
United States	Kootenai Cancer Clinic	Sandpoint	Idaho
United States	Community Medical Center	Scranton	Pennsylvania
United States	Kaiser Permanente Washington	Seattle	Washington
United States	Minor and James Medical PLLC	Seattle	Washington
United States	Pacific Gynecology Specialists	Seattle	Washington
United States	Swedish Medical Center-Ballard Campus	Seattle	Washington
United States	Swedish Medical Center-Cherry Hill	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	PeaceHealth United General Medical Center	Sedro-Woolley	Washington
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	HSHS Saint Nicholas Hospital	Sheboygan	Wisconsin
United States	Providence Regional Cancer System-Shelton	Shelton	Washington
United States	Welch Cancer Center	Sheridan	Wyoming
United States	LSU Health Sciences Center at Shreveport	Shreveport	Louisiana
United States	Dayton Physicians LLC-Wilson	Sidney	Ohio
United States	Hematology Oncology Associates of Illinois - Skokie	Skokie	Illinois
United States	North Shore Medical Center	Skokie	Illinois
United States	South Jordan Health Center	South Jordan	Utah
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	Evergreen Hematology and Oncology PS	Spokane	Washington
United States	MultiCare Deaconess Cancer and Blood Specialty Center - Downtown	Spokane	Washington
United States	MultiCare Deaconess Cancer and Blood Specialty Center - North	Spokane	Washington
United States	MultiCare Deaconess Cancer and Blood Specialty Center - Valley	Spokane Valley	Washington
United States	Central Illinois Hematology Oncology Center	Springfield	Illinois
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Springfield Regional Cancer Center	Springfield	Ohio
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Mitchell Folbe MD PC	Sterling Heights	Michigan
United States	Premier Hematology Oncology Care	Sterling Heights	Michigan
United States	Marshfield Medical Center-River Region at Stevens Point	Stevens Point	Wisconsin
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	BJC Outpatient Center at Sunset Hills	Sunset Hills	Missouri
United States	Southwest Illinois Health Services LLP	Swansea	Illinois
United States	ProMedica Flower Hospital	Sylvania	Ohio
United States	Mary Bridge Children's Hospital and Health Center	Tacoma	Washington
United States	MultiCare Tacoma General Hospital	Tacoma	Washington
United States	National Jewish Health-Northern Hematology Oncology	Thornton	Colorado
United States	Mercy Hospital of Tiffin	Tiffin	Ohio
United States	Mercy Health - Saint Anne Hospital	Toledo	Ohio
United States	ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital	Toledo	Ohio
United States	Saint Vincent Mercy Medical Center	Toledo	Ohio
United States	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio
United States	Toledo Community Hospital Oncology Program CCOP	Toledo	Ohio
United States	University of Toledo	Toledo	Ohio
United States	Smilow Cancer Hospital-Torrington Care Center	Torrington	Connecticut
United States	Munson Medical Center	Traverse City	Michigan
United States	Claudia BR Herke MD PC	Troy	Michigan
United States	Dayton Physicians LLC - Troy	Troy	Ohio
United States	Hematology Oncology Consultants PC-Troy	Troy	Michigan
United States	Michigan Institute of Urology-Town Center	Troy	Michigan
United States	Upper Valley Medical Center	Troy	Ohio
United States	William Beaumont Hospital - Troy	Troy	Michigan
United States	Banner University Medical Center - Tucson	Tucson	Arizona
United States	University of Arizona Cancer Center-North Campus	Tucson	Arizona
United States	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho
United States	Memorial Sloan Kettering Nassau	Uniondale	New York
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Saint Joseph Warren Hospital	Warren	Ohio
United States	Mercy Hospital Washington	Washington	Missouri
United States	Sibley Memorial Hospital	Washington	District of Columbia
United States	Marshfield Clinic-Wausau Center	Wausau	Wisconsin
United States	Fulton County Health Center	Wauseon	Ohio
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Henry Ford West Bloomfield Hospital	West Bloomfield	Michigan
United States	University of Cincinnati Cancer Center-West Chester	West Chester	Ohio
United States	Cleveland Clinic-Weston	Weston	Florida
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas
United States	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado
United States	Ascension Via Christi Hospitals Wichita	Wichita	Kansas
United States	Associates In Womens Health	Wichita	Kansas
United States	Cancer Center of Kansas - Wichita	Wichita	Kansas
United States	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas
United States	Wesley Medical Center	Wichita	Kansas
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Wright-Patterson Medical Center	Wright-Patterson Air Force Base	Ohio
United States	University of Michigan Health - West	Wyoming	Michigan
United States	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington
United States	Providence Regional Cancer System-Yelm	Yelm	Washington
United States	Saint Elizabeth Youngstown Hospital	Youngstown	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	Canadian Cancer Trials Group

Countries where clinical trial is conducted

United States,  Canada,  Israel,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Identification and characterization of the BCR/ABL1-like phenotype	Cox regression analysis will be used to assess whether BCR-ABL-like phenotype is an independent predictor for overall survival (and relapse-free survival), adjusted by treatment effect, minimal residual disease status, age, cytogenetic abnormalities, CD20 status, rituximab use, and whether patients intend to receive hematopoietic stem cell transplantation or not. If a strong interaction effect is detected, Cox regression analysis will be used to look at the treatment difference separately within each of the BCR-ABL-like phenotype categories (negative/positive) to see if the magnitude and direction of the treatment effect differs by phenotype.	Up to 2 years
Primary	Overall survival	Medians and confidence intervals will be calculated using the Kaplan-Meier method. Comparison of overall survival between treatment arms will be conducted using the one-sided stratified log-rank test with minimal residual disease status, age, CD20 status, rituximab use, and whether patients intend to receive hematopoietic stem cell transplantation or not as stratification factors. A Cox proportional hazards model will be used to assess the effect of treatment and will include receipt of transplant as a time-varying covariate.	Time between randomization and death from any cause, assessed up to 10 years
Secondary	Relapse-free survival	Estimates of relapse-free survival, including medians and confidence intervals, will be calculated using the Kaplan-Meier method. Comparison of relapse-free survival between treatment arms will be conducted using the one-sided stratified log-rank test with minimal residual disease status, age, CD20 status, rituximab use, and whether patients intend to receive hematopoietic stem cell transplantation or not as stratification factors. Stratified on those factors, Cox proportional hazards models, will also be used to assess the treatment effect by adjusting other possible clinical and biological risk factors, including cytogenetic abnormalities and the receipt of transplant (included as a time-varying covariate).	Time from randomization to relapse or death without documentation of relapse, assessed up to 10 years
Secondary	Minimal residual disease (MRD) status	Patients who are MRD positive at step 3 randomization/ registration and then convert to MRD negative (-) after 2 cycles of blinatumomab will be compared to those patients who are MRD- at randomization and remain MRD- after 2 cycles of blinatumomab or consolidation chemotherapy. The study will have 80% power to detect 56% reduction in hazard rate in the MRD- remain as MRD- patients (after blinatumomab/consolidation chemotherapy), using one-sided log rank test at the significance level of 0.025 and assuming 2 years of follow-up	Up to 32 weeks
Secondary	Incidence of adverse events	Will be assessed per the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Classified as either possibly, probably, or definitely related to study treatment. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated or unlikely to be related" to study treatment in the event of an actual relationship developing.	Up to 10 years