Blinatumomab and Combination Chemotherapy or Dasatinib, Prednisone, and Blinatumomab in Treating Older Patients With Acute Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

A Phase II Study of Blinatumomab and POMP (Prednisone, Vincristine, Methotrexate, 6-Mercaptopurine) for Patients ≥ 65 Years of Age With Newly Diagnosed Philadelphia-Chromosome Negative (Ph-) Acute Lymphoblastic Leukemia (ALL) and of Dasatinib, Prednisone and Blinatumomab for Patients ≥ 65 Years of Age With Newly Diagnosed Philadelphia-Chromosome Positive (Ph+) ALL, Relapsed/Refractory Philadelphia-Chromosome Positive (Ph+) ALL, and Philadelphia-Chromosome-Like Signature (Ph-Like) ALL With Known or Presumed Activating Dasatinib-Sensitive Mutations or Kinase Fusions (DSMKF)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02143414
• Other study ID #: NCI-2014-01047
• Secondary ID: NCI-2014-01047SW
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 30, 2015
• Est. completion date: October 23, 2024

Study information

• Verified date: May 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial studies the side effects and how well blinatumomab and combination chemotherapy or dasatinib, prednisone, and blinatumomab work in treating older patients with acute lymphoblastic leukemia. 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. Chemotherapy drugs, such as prednisone, vincristine sulfate, methotrexate, and mercaptopurine, 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. Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving blinatumomab with combination chemotherapy or dasatinib and prednisone may kill more cancer cells.

Description:

PRIMARY OBJECTIVES:

I. To evaluate the 3-year survival rate in elderly patients with newly diagnosed Philadelphia (Ph)-negative acute lymphoblastic leukemia (ALL) treated with blinatumomab followed by POMP (prednisone, vincristine sulfate, methotrexate, and mercaptopurine) maintenance.

II. To evaluate in a preliminary manner (feasibility study) the safety of dasatinib-steroid based induction followed by blinatumomab treatment in combination with dasatinib followed by dasatinib-based maintenance in patients with newly diagnosed Ph-positive ALL, relapsed/refractory Ph-positive ALL, and Ph-like dasatinib-sensitive mutations or kinase fusions (DSMKF) ALL (newly-diagnosed relapsed or refractory).

SECONDARY OBJECTIVES:

I. To evaluate toxicities in these patient populations treated with these regimens.

II. To estimate the rates of complete response (CR), complete remission with incomplete count recovery (CRi) and disease-free survival in Ph-negative patients.

III. To estimate disease-free and overall survival in Ph-positive ALL and Ph-like DSMKF ALL.

IV. To estimate in each cohort the rate of minimal residual disease (MRD) negativity, and the time to achieve MRD negativity (exploratory analysis).

V. To determine whether anti-idiotype antibodies directed against blinatumomab develop with blinatumomab treatment in this study.

ADDITIONAL TRANSLATIONAL MEDICINE OBJECTIVES:

I. To estimate the incidence of the Ph-like signature in elderly patients (>= 65 years of age) with newly diagnosed Philadelphia-chromosome negative ALL.

II. To estimate the incidence of the various tyrosine-kinase fusions, making up the Ph-like signature in elderly patients with newly diagnosed Philadelphia-chromosome negative ALL.

III. To evaluate outcomes (event free survival [EFS] and overall survival [OS]) in patients with the Ph-like signature versus those without the Ph-like signature in Ph-negative ALL.

IV. To describe via single cell transcriptomics the clonal diversity in gene expression of participants on the trial.

V. To describe the methylation status of the overall genome as well as key driver genes of all participants in the trial.

OUTLINE: Patients are assigned to 1 of 2 treatment cohorts according to Philadelphia chromosome status.

COHORT I (PHILADELPHIA CHROMOSOME NEGATIVE PATIENTS):

INDUCTION: Patients receive blinatumomab intravenously (IV) continuously over 24 hours on days 1-28 in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray and echocardiography (ECHO) during screening and a computed tomography (CT) scan and/or magnetic resonance imaging (MRI) as well as blood sample collection and bone marrow aspiration and biopsy throughout the trial. Patients undergo a lumbar puncture during screening and on study. Patients may also undergo a biopsy during screening. (Closed to accrual 06/29/17)

RE-INDUCTION: Patients not achieving CR or CRi after Induction, receive blinatumomab IV continuously over 24 hours on days 1-28 in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray and ECHO during screening and a CT scan and/or MRI as well as blood sample collection and bone marrow aspiration and biopsy throughout the trial. Patients undergo a lumbar puncture during screening and on study. Patients may also undergo a biopsy during screening.

POST-REMISSION: Patients receive blinatumomab IV continuously over 24 hours on days 1-28. Treatment repeats every 42 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan and/or MRI on study and during follow-up. Patients also undergo blood sample collection, lumbar puncture, and bone marrow aspiration and biopsy on study.

MAINTENANCE: Patients receive prednisone orally (PO) on days 1-5, vincristine sulfate IV on day 1, mercaptopurine PO on days 1-28, and methotrexate PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 18 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan and/or MRI on study and during follow-up. Patients also undergo a lumbar puncture and bone marrow aspiration and biopsy on study.

COHORT II (PHILADELPHIA CHROMOSOME POSITIVE PATIENTS):

INDUCTION: Patients receive dasatinib PO on days 1-84 and prednisone PO on days 1-24 with tapering on days 25-32 in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray and ECHO during screening and a CT scan and/or MRI throughout the trial. Patients undergo a lumbar puncture and bone marrow aspiration and biopsy during screening and on study. Patients may also undergo a biopsy during screening.

RE-INDUCTION: Patients receive blinatumomab IV continuously over 24 hours on days 1-28. Treatment repeats every 42 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan and/or MRI on study and during follow-up. Patients also undergo blood sample collection, a lumbar puncture, and bone marrow aspiration and biopsy on study.

POST-REMISSION: Patients receive blinatumomab IV continuously over 24 hours on days 1-28 and dasatinib PO on days 1-42. Treatment repeats every 42 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan and/or MRI on study and during follow-up. Patients also undergo blood sample collection, lumbar puncture, and bone marrow aspiration and biopsy on study.

MAINTENANCE: Patients receive dasatinib PO on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive prednisone PO on days 1-5. Treatment repeats every 28 days for 18 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan and/or MRI as well as a lumbar puncture and bone marrow aspiration and biopsy on study.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 2 years, and then annually until 10 years from initial registration.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 53
• Est. completion date: October 23, 2024
• Est. primary completion date: June 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

Inclusion Criteria:

• Registration Step 1 - Induction/Re-Induction:

• Patients must have a new morphologic diagnosis of precursor B cell acute lymphoblastic leukemia (ALL) (non T cell) based on World Health Organization (WHO) criteria; patients with Burkitt's (L3) are excluded; patients with Ph-positive or Ph-like ALL with dasatinib-sensitive mutations or kinase fusions may have relapsed or refractory diagnoses

• NOTE: Relapsed/refractory Ph-positive patients or Ph-like patients with dasatinib-sensitive mutations or kinase fusions who have previous exposure to either dasatinib or another 2nd or 3rd generation tyrosine kinase inhibitor (TKI) will begin protocol therapy with Cohort 2: re-induction cycle 1

• Patients must have a diagnosis of Philadelphia chromosome negative ALL or Ph chromosome positive ALL by cytogenetics, fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR); patients will be registered to receive treatment in either Cohort 1 (Ph-) or Cohort 2 (Ph+ or Ph-like DSMKF) based on these results; diagnostic specimens must be submitted to the site's local Clinical Laboratory Improvement Amendments (CLIA)-approved cytogenetics laboratory and results of tests (cytogenetics, FISH or PCR) must confirm Ph status prior to registration; if not already known, breakpoint cluster region- abelson murine leukemia viral oncogene homolog 1 (BCR-ABL) status (p190 or p210) must be evaluated in Ph-positive patients by PCR

• For Cohort 2, Ph-like testing is not required specifically for this study; however, to be registered to Cohort 2 under the Ph-like DSMKF criterion, the patient must have a known or presumed activating Ph-like signature and dasatinib-sensitive mutation or kinase fusion, such as: ABL1, ABL2, colony stimulating factor 1 receptor (CSF1R), platelet derived growth factor receptor beta (PDGFRB), platelet derived growth factor receptor alpha (PDGFRA), or fibroblast growth factor receptor (FGFR)s that was otherwise identified as part of normal standard of care; prior to registering any patients with a known or presumed activating Ph-like signature and dasatinib-sensitive mutations or kinase fusions (DSMKF) treating physicians must confirm eligibility with the study chairs via email; the study chairs must respond via email with confirmation of patient eligibility prior to patient registration

• All newly diagnosed patients must have evidence of ALL in their marrow or peripheral blood with at least 20% lymphoblasts present in blood or bone marrow collected within 28 days prior to registration; all relapsed/refractory patients (Cohort 2) must have at least 5% lymphoblasts present in blood or bone marrow collected within 28 days prior to registration; for relapsed/refractory patients, pathology and cytogenetics reports (both from time of original diagnosis) must be submitted at time of registration; if a bone marrow aspirate cannot be obtained despite an attempt (dry tap), appropriate immunohistochemistry (IHC) testing, including cluster of differentiation (CD)19, must be performed on the bone marrow biopsy to determine lineage; for ALL in marrow or peripheral blood, immunophenotyping of the blood or marrow lymphoblasts must be performed to determine lineage (B cell, T cell or mixed B/T cell); appropriate marker studies including CD19 (B cell), must be performed; co-expression of myeloid antigens (CD13 and CD33) will not exclude patients; if possible, the lineage specific markers (myeloid cells) should be determined; the blood/bone marrow sample for these assays must be obtained within 28 days prior to registration; patients with only extramedullary disease in the absence of bone marrow or blood involvement are not eligible

• 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, active ALL in the CNS confirmed by cerebrospinal fluid (CSF) analysis, or other significant CNS abnormalities

• Patients must have a lumbar puncture to determine CNS involvement of ALL within 14 days prior to registration; patients with CNS3 are excluded from the trial; patients with CNS1 or CNS2 will be eligible, but will be monitored for CNS involvement; note that intrathecal methotrexate administered during the pre-study lumbar puncture may count as the first dose of intrathecal therapy required as part of the study

• Cohort I, Ph-negative Patients Only: Patients must not have received any prior chemotherapy, radiation therapy, or other therapy for the treatment of ALL (other than those noted below) and must not be receiving any immunosuppressive therapy; patients may not have received any prior investigational therapy within 28 days prior to registration; patients must not have received any monoclonal antibody therapy within 42 days of registration; patients may have received the following within any time prior to registration: low dose chemotherapy-including: cyclophosphamide 1 g/m^2, oral 6-mercaptopurine, or oral methotrexate (other low dose chemotherapy may be allowable, however any other options not listed here should be confirmed with the study chairs), TKI therapy, steroids, hydroxyurea, leukapheresis, intrathecal chemotherapy or vincristine

• Cohort I, Ph-negative Patients Only: In the event that the patient's bone marrow blast count is >= 50% blasts, patients may be registered but should receive steroids for 3-5 days in order to reduce tumor burden prior to blinatumomab administration, as follows

• Prephase treatment with dexamethasone (10-20 mg/m^2) for 3-5 days is required for patients with bone marrow blasts >= 50%, peripheral blood blasts 15,000/uL or higher, or elevated lactate dehydrogenase (LDH) suggesting rapidly progressive disease per investigator opinion

• Pre-treatment should conclude at least 24 hours prior to the first dose of blinatumomab (although additional dexamethasone is automatically given as a pre-med prior to the first dose); at the time of first infusion of blinatumomab, the absolute peripheral blast count should be < 25,000/uL

• Note: For the purposes of the study, day 1 of the cycle will be the first day of blinatumomab administration

• Cohort I, Ph-negative Patients Only: It is preferred, but not required, that corticosteroids and hydroxyurea should start only after all diagnostic samples have been obtained; however, if the patient was previously on corticosteroids and/or hydroxyurea, this is allowable provided that the patient still has measurable disease at time of the bone marrow aspirate

• Corticosteroids and/or hydroxyurea, as well as any of the other therapies mentioned (with the exception of IV cyclophosphamide), may continue to be administered, at physician discretion, until 1 day prior to blinatumomab administration

• IV cyclophosphamide must be discontinued at least 7 days prior to blinatumomab administration

• Cohort 2, Ph-positive and Ph-like DSMKF Patients Only: Patients must NOT have received a prior autologous or allogeneic hematopoietic stem cell transplant at any time. Patients must NOT have received any chemotherapy, investigational agents, or undergone major surgery within 14 days prior to registration, with the following exceptions:

• Monoclonal antibodies must not have been received for 1 week prior to registration

• Chimeric antigen receptor (CAR) T-cells must not have been received for 28 days prior to registration

• Steroids, hydroxyurea, vincristine, 6-mercaptopurine, methotrexate, thioguanine and intrathecal chemotherapy are permitted within any timeframe prior to registration; Food and Drug Administration (FDA)-approved TKIs may also be administered until 1 day prior to start of study therapy (C1, D1); IV cyclophosphamide may be administered at doses of 1 g/m^2 or less until up to 7 days prior to registration

• Patients must be >= 65 years of age; for patients 65-69 years of age, patient must be deemed not suitable for standard intensive induction chemotherapy at the discretion of the local investigator, or must have refused standard intensive chemotherapy

• Cohort I, Ph-negative Patients Only: Patients must not be candidates for allogeneic hematopoietic stem cell transplant; NOTE: Subjects up to age 70 years who are considered fit for allogeneic hematopoietic stem cell transplant, should be considered for enrollment on E1910, in order to avoid competing with that study; if a patient is considered unfit for intensive chemotherapy at the time of initial diagnosis, but subsequently achieves a complete remission (CR), then it will be left to the treating physician's discretion to consider hematopoietic stem cell transplant (HSCT)

• Cohort I, Ph-negative Patients Only: Patients must have complete history and physical examination within 28 days prior to registration

• Cohort I, Ph-negative Patients Only: Patients must have a Zubrod performance status of 0-2

• Cohort I, Ph-negative Patients Only: Patients must have serum creatinine =< 1.5 mg/dl within 14 days prior to registration

• Cohort I, Ph-negative Patients Only: Patients must have aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 x institutional upper limit of normal (IULN) within 14 days prior to registration

• Cohort I, Ph-negative Patients Only: Patients must have total bilirubin =< 2.0 x IULN within 14 days prior to registration

• Cohort I, Ph-negative Patients Only: Patients must have alkaline phosphatase =< 2.5 x IULN within 14 days prior to registration

• Cohort I, Ph-negative Patients Only: Patients must not have systemic fungal, bacterial, viral or other infection that is not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment)

• Cohort I, Ph-negative Patients Only: Patients must not have Common Terminology Criteria for Adverse Events (CTCAE) >= grade 2 neuropathy (cranial, motor or sensory) within 14 days prior to registration

• Cohort I, Ph-negative Patients Only: Patients known to be positive for HIV (the human immunodeficiency virus) may be eligible, providing they meet the following additional criteria within 28 days prior to registration:

• No history of acquired immune deficiency syndrome (AIDS)-defining conditions

• CD4 cells > 350 cells/mm^3

• If on antiretroviral agents, must not include zidovudine or stavudine

• Viral load =< 50 copies HIV messenger ribonucleic acid (mRNA)/mm^3 if on combination antiretroviral therapy (cART) or =< 25,000 copies HIV mRNA/mm^3 if not on cART

• Highly active antiretroviral therapy (HAART) regimens are acceptable providing they have only weak P450A4 interactions

• Cohort I, Ph-negative Patients Only: Patients must not have any known autoimmune disease

• Cohort I, Ph-negative Patients Only: Patients must not have testicular involvement; if clinical or ultrasound findings are equivocal, biopsy must be performed; all tests for establishing testicular involvement must be completed within 14 days prior to registration

• Cohort I, Ph-negative Patients Only: Patients with evidence of extramedullary disease at diagnosis will have computed tomography (CT) scan or magnetic resonance imaging (MRI) of the chest, abdomen and pelvis to obtain baseline values within 28 days prior to registration

• Cohort I, Ph-negative Patients Only: No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years

• Cohort I, Ph-negative Patients Only: Patients must have the following tests within 28 days prior to registration to obtain baseline measurements:

• Prothrombin time (PT)/partial thromboplastin time (PTT)/international normalized ratio (INR)/fibrinogen (all patients)

• Cohort 1, Ph- Patients Only: Neurologic assessment

• Cohort 2, Ph+ and Ph-like DSMKF Patients Only: Patients must not have active pericardial effusion, ascites or pleural effusion of any grade based on chest x-ray and echocardiogram within 28 days prior to registration; exception: if the effusion is suspected to be related to the leukemia, the patient may have pericardial effusion =< grade 2 or pleural effusion =< grade 1

• Cohort 2, Ph+ and Ph-like DSMKF Patients Only: Patients must have ejection fraction >= 45% based on echocardiogram performed within 28 days prior to registration

• Cohort 2, Ph+ and Ph-like DSMKF Patients Only: Patients must have QTcF (by Fridericia calculation) < 480/msec based on electrocardiogram (EKG) performed within 28 days prior to registration

• Cohort 2, Ph+ and Ph-like DSMKF Patients Only: Patients must not be receiving any proton pump inhibitors at the time of registration

• Pretreatment cytogenetics must be performed on all patients; collection of pretreatment specimens must be completed within 28 days prior to registration to S1318; specimens must be submitted to the site's preferred CLIA-approved cytogenetics laboratory; BCR-ABL status must be verified in Ph-positive patients by FISH, cytogenetics, and/or PCR prior to enrollment; if a patient is Ph-positive, PCR for both p190 and p210 must be sent

• Patients must be offered participation in specimen submission for future research; with patient's consent, specimens must be submitted as outlined

• Cohort 1, Ph-negative Patients Only: Patients must have specimens submitted for blinatumomab immunogenicity assessment; collection of pretreatment specimens must be completed within 28 days prior to registration to S1318; specimens must be submitted to LabConnect

• Cohort 2, Ph-positive and Ph-like DSMKF Patients Only: Patients must agree to have specimens submitted for blinatumomab immunogenicity testing if subsequently moved to a blinatumomab containing treatment regimen on protocol

• Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines

• As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

• Registration Step 2 - Post-Remission Therapy:

• Cohort 1, Ph-negative Patients Only: Patients must have achieved CR or CRi within 2 cycles of induction/re-induction with blinatumomab

• NOTE: day 1 of post-remission = day 43 of the preceding cycle (+/- 3 days)

• Cohort 2, Ph-positive and Ph-like DSMKF Patients Only: Newly diagnosed Ph+, newly-diagnosed Ph-like DSMKF, and relapsed/refractory Ph+ patients without prior dasatinib or other 2nd or 3rd generation TKI therapy, must have achieved CR or CRi within 1 cycle of induction with dasatinib/prednisone, or within 2 cycles of re-induction with blinatumomab; relapsed/refractory Ph+ or Ph-like DSMKF patients with prior dasatinib or other 2nd or 3rd generation TKI therapy must have achieved CR or CRi within 2 cycles of re-induction therapy with blinatumomab

• NOTE: day 1 of post-remission = day 85 of the preceding induction cycle (+/- 3 days), or day 43 of the preceding re-induction cycle (+/- 3 days) as applicable

• Serum creatinine =< 1.5 mg/dl within 14 days prior to registration

• AST and ALT =< 3.0 x institutional upper limit of normal (IULN) within 14 days prior to registration

• Total bilirubin =< 2.0 x IULN within 14 days prior to registration

• Absolute neutrophil count (ANC) >= 750/mcL within 28 days prior to registration

• Platelets >= 50,000/mcL within 28 days prior to registration

• Patients must be registered to Step 2 within 28 days after count recovery; (Note:

there is no maximum allotted time period for count recovery, providing patient remains in CR or CRi)

• All non-hematologic treatment related toxicities that are deemed clinically significant by the treating investigator must have resolved to =< grade 2

• Registration Step 3 - Maintenance: Patients must have documented CR or CRi within 28 days prior to registration; note that bone marrow examination is only required if there are clinical signs/symptoms of progression; if progression is a concern due to the length of the time for count recovery, a bone marrow examination is recommended

• Registration Step 3 - Maintenance: Patients must have serum creatinine =< 1.5 mg/dl within 14 days prior to registration

• Registration Step 3 - Maintenance: Patients must have AST and ALT =< 3.0 x institutional upper limit of normal (IULN) within 14 days prior to registration

• Registration Step 3 - Maintenance: Patients must have total bilirubin < 2.0 x institutional upper limit of normal (IULN) within 14 days prior to registration

• Registration Step 3 - Maintenance: Patients must have adequate marrow function as evidenced by ANC >= 750/mcL within 28 days prior to registration

• Registration Step 3 - Maintenance: Patients must have adequate marrow function as evidenced by platelets >= 75,000/mcL within 28 days prior to registration

• Registration Step 3 - Maintenance: All non-hematologic treatment related toxicities that are deemed clinically significant by the treating investigator must have resolved to =< grade 2

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• B Acute Lymphoblastic Leukemia
• B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1
• Leukemia
• Leukemia, Lymphoid
• Philadelphia Chromosome
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Recurrent Acute Lymphoblastic Leukemia
• Refractory Acute Lymphoblastic Leukemia

Intervention

Procedure:
• Biopsy
Undergo a biopsy
• Biospecimen Collection
Undergo a blood sample collection

Biological:
• Blinatumomab
Given IV

Procedure:
• Bone Marrow Aspiration and Biopsy
Undergo a bone marrow aspiration and biopsy
• Computed Tomography
Undergo a CT scan

Drug:
• Dasatinib
Given PO

Procedure:
• Echocardiography
Undergo ECHO
• Lumbar Puncture
Undergo a lumbar puncture
• Magnetic Resonance Imaging
Undergo MRI

Drug:
• Mercaptopurine
Given PO
• Methotrexate
Given PO
• Methotrexate Sodium
Given PO
• Prednisone
Given PO
• Vincristine
Given IV
• Vincristine Sulfate
Given IV

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

Locations

Country	Name	City	State
United States	Hickman Cancer Center	Adrian	Michigan
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	McFarland Clinic - Ames	Ames	Iowa
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Northside Hospital	Atlanta	Georgia
United States	Augusta University Medical Center	Augusta	Georgia
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	Nebraska Medicine-Bellevue	Bellevue	Nebraska
United States	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	OSF Saint Joseph Medical Center	Bloomington	Illinois
United States	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina
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	Cox Cancer Center Branson	Branson	Missouri
United States	Roswell Park Cancer Institute	Buffalo	New York
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	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Miami Valley Hospital South	Centerville	Ohio
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
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	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Oncology Hematology Care Inc-Crestview	Crestview Hills	Kentucky
United States	Baylor University Medical Center	Dallas	Texas
United States	Carle at The Riverfront	Danville	Illinois
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	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	Prisma Health Cancer Institute - Easley	Easley	South Carolina
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Oncology Hematology Care Inc-Healthplex	Fairfield	Ohio
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Sanford Clinic North-Fargo	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Beaumont Hospital - Farmington Hills	Farmington Hills	Michigan
United States	Weisberg Cancer Treatment Center	Farmington Hills	Michigan
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	McFarland Clinic - Trinity Cancer Center	Fort Dodge	Iowa
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Western Illinois Cancer Treatment Center	Galesburg	Illinois
United States	Corewell Health Grand Rapids Hospitals - Butterworth Hospital	Grand Rapids	Michigan
United States	Trinity Health Grand Rapids Hospital	Grand Rapids	Michigan
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	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	Wayne Hospital	Greenville	Ohio
United States	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	William Beaumont Hospital-Grosse Pointe	Grosse Pointe	Michigan
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Franciscan Health Indianapolis	Indianapolis	Indiana
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	McFarland Clinic - Jefferson	Jefferson	Iowa
United States	MU Health Care Goldschmidt Cancer Center	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	University of Kansas Cancer Center	Kansas City	Kansas
United States	ECU Health Oncology Kenansville	Kenansville	North Carolina
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	ECU Health Oncology Kinston	Kinston	North Carolina
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Northwell Health/Center for Advanced Medicine	Lake Success	New York
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Cancer Center of Kansas-Liberal	Liberal	Kansas
United States	John L McClellan Memorial Veterans Hospital	Little Rock	Arkansas
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Los Angeles General Medical Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	North Shore University Hospital	Manhasset	New York
United States	McFarland Clinic - Marshalltown	Marshalltown	Iowa
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio
United States	Toledo Radiation Oncology at Northwest Ohio Onocolgy Center	Maumee	Ohio
United States	Cancer Center of Kansas - McPherson	McPherson	Kansas
United States	Franciscan Saint Anthony Health-Michigan City	Michigan City	Indiana
United States	Woodland Cancer Care Center	Michigan City	Indiana
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Toledo Clinic Cancer Centers-Monroe	Monroe	Michigan
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Trinity Health Muskegon Hospital	Muskegon	Michigan
United States	Smilow Cancer Center/Yale-New Haven Hospital	New Haven	Connecticut
United States	Yale University	New Haven	Connecticut
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	UC Comprehensive Cancer Center at Silver Cross	New Lenox	Illinois
United States	USC Norris Oncology/Hematology-Newport Beach	Newport Beach	California
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	Corewell Health Lakeland Hospitals - Niles Hospital	Niles	Michigan
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Nebraska Medicine-Village Pointe	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	Saint Charles Hospital	Oregon	Ohio
United States	Orlando Health Cancer Institute	Orlando	Florida
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Radiation Oncology of Northern Illinois	Ottawa	Illinois
United States	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	Keck Medical Center of USC Pasadena	Pasadena	California
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	OSF Saint Francis Radiation Oncology at Pekin	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	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Cancer Center of Kansas - Pratt	Pratt	Kansas
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Corewell Health Reed City Hospital	Reed City	Michigan
United States	ECU Health Oncology Richlands	Richlands	North Carolina
United States	Reid Health	Richmond	Indiana
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Corewell Health Lakeland Hospitals - Saint Joseph Hospital	Saint Joseph	Michigan
United States	Mercy Hospital Saint Louis	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	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	LSU Health Sciences Center at Shreveport	Shreveport	Louisiana
United States	Siouxland Regional Cancer Center	Sioux City	Iowa
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	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	BJC Outpatient Center at Sunset Hills	Sunset Hills	Missouri
United States	Mercy Health - Saint Anne Hospital	Toledo	Ohio
United States	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio
United States	Munson Medical Center	Traverse City	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	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas
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	Rush-Copley Healthcare Center	Yorkville	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival Rate (Cohort I)	To evaluate the 3-year overall survival rate in elderly participants with newly diagnosed Ph-negative ALL treated with blinatumomab followed by POMP maintenance. Overall	From the day of registration on study until death from any cause, assessed at 3 years
Primary	Incidence of Dose-limiting Toxicity (Cohort II)	Defined as any grade 4 or higher treatment-related, non-hematologic toxicity in the first cycle of post-remission therapy (blinatumomab/dasatinib) graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Only participants with Ph-positive ALL or Ph-like DSMKF ALL were evaluated.	Up to day 42 of post-remission therapy
Secondary	Number of Participants With Grade 3 Through 5 Adverse Events That Are Related to Study Drugs	Number of participants with Grade 3-5 adverse events that are possibly, probably or definitely related to study drug are reported by given type of adverse event. Adverse Events reported using CTCAE v 4.0, whereas Serious Adverse Events were reported with CTCAE v 5.0.	Duration of treatment and follow up until death or date of primary analysis (about 7.5 years)
Secondary	Complete Response Rate (Cohort I)	Complete response rate is measured by the number of participants achieving complete remission (CR) or complete remission with incomplete platelet recovery (CRi) rate. CR is defined as having <5% marrow aspirate blasts, ANC >1,000/mcL, platelets > 100,000/mcL, no blasts in peripheral blood, and C1 extramedullary disease status. CRi is the same as CR but platelet count may be <= 100,000/mcL and/or ANC <=1,000/mcL.	Participants are assessed after induction treatment and again after re-induction treatment, if re-induction treatment is received (i.e. up to 85 days after registration)
Secondary	Disease-free Survival (Cohort II)	An estimate of disease free survival in Ph-positive ALL and Ph-like DSMKF ALL (Cohort II). Disease free survival is measured by the number of years between the date the patient first achieves complete remission (CR) or complete remission with incomplete platelet recovery (CRi) until relapse from CR/CRi or death from any cause. CR is defined as having <5% marrow aspirate blasts, ANC >1,000/mcL, platelets > 100,000/mcL, no blasts in peripheral blood, and C1 extramedullary disease status. CRi is the same as CR but platelet count may be <= 100,000/mcL and/or ANC <=1,000/mcL.	Duration of treatment and follow up until death or date of primary analysis (about 7.5 years)
Secondary	Overall Survival (Cohort II)	Estimated using the method of Kaplan-Meier.	Up to 10 years
Secondary	Minimal Residual Disease Negativity	To estimate in each cohort the rate of minimal residual disease (MRD) negativity.	Participants are assessed after induction treatment and again after re-induction treatment, if re-induction treatment is received (i.e. up to 85 days after registration)
Secondary	Time to Achieve Minimal Residual Disease Negativity	Will be examined separately in descriptive analyses within each cohort.	Up to 10 years
Secondary	Anti-idiotype Antibody Development	To determine whether anti-idiotype antibodies directed against blinatumomab develop with blinatumomab treatment in this study.	Up to 10 years