Lenalidomide With or Without Epoetin Alfa in Treating Patients With Myelodysplastic Syndrome and Anemia

Anemia Clinical Trial

Official title:

Randomized Phase III Trial Comparing the Frequency of Major Erythroid Response (MER) to Treatment With Lenalidomide (Revlimid�) Alone and in Combination With Epoetin Alfa (Procrit�) in Subjects With Low- or Intermediate-1 Risk MDS and Symptomatic Anemia

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00843882
• Other study ID #: NCI-2009-01173
• Secondary ID: NCI-2009-01173CD
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 29, 2009
• Est. completion date: September 21, 2024

Study information

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

Clinical Trial Summary

This randomized phase III trial studies lenalidomide to see how well it works with or without epoetin alfa in treating patients with myelodysplastic syndrome and anemia. Lenalidomide may stop the growth of myelodysplastic syndrome by blocking blood flow to the cells. Colony stimulating factors, such as epoetin alfa, may increase the number of immune cells found in bone marrow or peripheral blood. It is not yet known whether lenalidomide is more effective with or without epoetin alfa in treating patients with myelodysplastic syndrome and anemia.

Description:

PRIMARY OBJECTIVE: I. To compare the rate of major erythroid response (MER) between lenalidomide monotherapy and combined treatment of lenalidomide and epoetin alfa in erythropoietin non-responsive low-/intermediate-1 (Int-1)-risk myelodysplastic syndrome (MDS) patients or erythropoietin treatment naïve patients with low probability of erythropoietin benefit. SECONDARY OBJECTIVES: I. To compare the time to MER by treatment assignment. II. To evaluate the duration of MER by treatment assignment. III. To estimate the frequency of MER to salvage combination therapy in patients who fail to experience a MER with lenalidomide monotherapy. IV. To evaluate and compare the frequency of minor erythroid response by treatment assignment. V. To investigate the mechanism and target of lenalidomide action in patients with chromosome 5q31.1 deletion. VI. To evaluate the frequency of cytogenetic response and progression, and the relation between cytogenetic pattern and erythroid response. VII. To evaluate the frequency of bone marrow response (complete response [CR] + partial response [PR]). VIII. To evaluate the relationship between erythroid response and laboratory correlates outlined below: VIIIa. Pretreatment and on study endogenous erythropoietin level (Arm A). VIIIb. To evaluate the effect of CD45 isoform profile on lenalidomide enhancement of erythropoietin-induced STAT5 phosphorylation in CD71^Hi erythroid precursors and the relationship to erythroid response. VIIIc. To characterize molecular targets relevant to lenalidomide cytotoxicity in del5q31.1 cells. VIIId. To evaluate the frequency of cryptic chromosome 5q31.1 deletions in patients with non-del5q31.1 MDS by array-based genomic scan, and to determine the relationship to hematologic response. OUTLINE: Patients are randomized to 1 of 2 treatment arms. Patients with del 5q31.1 karyotype are assigned to Arm A. ARM A: Patients receive lenalidomide orally (PO) once daily (QD) on days 1-21. Patients undergo bone marrow biopsy at screening and during follow-up. Patients undergo blood specimen collection on study. ARM B: Patients receive lenalidomide PO QD on days 1-21 and epoetin alfa subcutaneously (SC) once weekly. Patients undergo bone marrow biopsy at screening and during follow-up. Patients undergo blood specimen collection on study. In both arms, treatment repeats every 28 days for 4 cycles. Patients who achieve a major erythroid response (MER) may continue treatment beyond 4 cycles in the absence of disease progression, disease conversion to acute myeloid leukemia, or unacceptable toxicity. Patients in Arm A who fail to achieve MER or who achieve MER but relapse after 16 weeks of treatment with lenalidomide may crossover and receive treatment in Arm B. After completion of study treatment, patients are followed up for 6 months.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 247
• Est. completion date: September 21, 2024
• Est. primary completion date: July 8, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age >= 18 years
• NOTE: Results of the bone marrow biopsy and aspirate as well as cytogenetics are mandatory to register subjects onto study, which are indispensable to determine International Prognostic Scoring System (IPSS) category needed for eligibility; please note that it is not necessary to wait for the week 16, week 32, or week bone marrow and cytogenetic results prior to starting the next cycle unless deemed necessary by the treating physician; one example of this exception can include if the subject shows signs of progression, such as increased peripheral blood blast percentage; at that juncture, the treating physician may prefer to await the results prior to starting a new cycle; if a cycle is started, and based on the bone marrow results it is felt by the treating physician that the subject should not continue on treatment, please be sure to note this information on the case report forms at end of treatment
• Patient must have documented diagnosis of MDS lasting at least three months (MDS duration >= 3 months) according to World Health Organization (WHO) criteria or non-proliferative chronic myelomonocytic leukemia (CMML) (white blood cell [WBC] < 12,000/mcL)
• Patient must have International Prognostic Scoring System (IPSS) categories of low- or intermediate-1-risk disease; patients must have IPSS score determined by cytogenetic analysis prior to randomization; patients must have cytogenetic analysis done (to calculate IPSS); if the current bone marrow biopsy is a dry tap, patients with cytogenetic failure and < 10% marrow blasts will be eligible; subjects with cytogenetic failure must have previous cytogenetic results (fluorescence in situ hybridization [FISH] is not a substitute) within the last 6 months post last type of MDS treatment (in this case, not referring to growth factors as type of MDS treatment)
• Must have symptomatic anemia untransfused with hemoglobin < 9.5 g/dL =< 8 weeks prior to randomization or with red blood cells (RBC) transfusion dependence (i.e., >= 2 units/month) confirmed for =< 8 weeks before randomization
• NOTE: For non-transfusion dependent patients (i.e., receiving < 2 units/4 weeks x 8 weeks pre-study) who receive periodic transfusions, the mean 8 week pre-transfusion hemoglobin should be used to determine protocol eligibility and response reference
• For non-transfusion dependent patients, a minimum of 2 pre-transfusion or un-transfused hemoglobin values are required
• Applies only for patients without the deletion 5q 31.1; patients must have failed treatment with an erythropoietic growth factor, or have a low probability of response to rhu-erythropoietin; patients with low probability of response to rhu-erythropoietin

or prior erythropoietin failures are defined as follows:

• Prior erythropoietin failure-requires a minimum trial of >= 40,000 units epoetin alfa/week x 8 weeks or equivalent dose of darbepoetin alfa for 8 weeks with failure to achieve transfusion independence in dependent patients or a failure to achieve a >= 2 g rise in hemoglobin sustained for >= 4 weeks in non-transfusion dependent patients
• Low erythropoietin response profile-rhu-erythropoietin and epoetin alfa-naïve patients receiving >= 2U packed (p)RBC/month for a minimum of 8 weeks, and serum erythropoietin > 500 mU/mL in the 8 weeks prior to randomization for a hemoglobin < 9.5 g/dL
• Patients must be off all non-transfusion therapy for MDS for 28 days prior to initiation of study treatment, including all types of growth factors; patients may receive hydrocortisone prophylactically to prevent transfusion reactions
• Patients must have a serum erythropoietin level documented before randomization and =< 56 days before day 1 of study treatment; NOTE: hemoglobin must be < 9.5 g/dL at time that serum erythropoietin is drawn
• Effective contraception must be used by patients participating in lenalidomide therapy, and all patients must agree to counseling by a trained counselor every 28 days about pregnancy precautions and risks of fetal exposure; females of childbearing potential (FCBP) must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control: one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide, during lenalidomide therapy, during dose interruptions, and for at least 28 days following discontinuation of lenalidomide therapy; females of childbearing potential should be referred to a qualified provider of contraceptive methods, if needed; males receiving lenalidomide must agree to use a latex condom during any sexual contact with females of childbearing potential even if they have undergone a successful vasectomy
• Platelet count >= 50,000/mcL (50 x 10^9/L) without platelet transfusion (within 56 days prior to randomization)
• Absolute neutrophil count (ANC) >= 500 cells/mcL (0.5 x 10^9/L); hence ANC must be >= 500/mcL without myeloid growth factor support (within 56 days prior to randomization)
• Serum creatinine =< 1.5 times upper limit of normal (ULN) (within 56 days prior to randomization)
• Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) or serum glutamate pyruvate transaminase (SGPT)/alanine aminotransferase (ALT) =< 2.0 x ULN (within 56 days prior to randomization)
• Serum total bilirubin < 3.0 mg/dL (within 56 days prior to randomization)
• Inclusion criteria for crossover registration from Arm A (lenalidomide alone) to Arm B

(lenalidomide and epoetin alfa):

• Patients must have completed 16 weeks of monotherapy with lenalidomide
• Patients must show failure to achieve MER (major erythroid response) or have achieved MER but relapsed on Arm A

Exclusion Criteria:

• Patients must not have documented iron deficiency; all patients must have documented marrow iron stores; if marrow iron stain is not available, the transferrin saturation must be > 20% or a serum ferritin > 100 ng/mL
• Women must not be pregnant or breastfeeding; females of childbearing potential must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10-14 days and again within 24 hours prior to starting cycle 1 of lenalidomide; a female of childbearing potential (FCBP) is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) 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; FCBP must also agree to ongoing pregnancy testing)
• Patients must not have prior therapy with lenalidomide
• Patients must not have a diagnosis of uncontrolled seizure or uncontrolled hypertension
• Patients must not have proliferative (WBC >= 12,000/mcL) chronic myelomonocytic leukemia (CMML); WBC must be < 12,000/mcL
• Patients must not have MDS secondary to treatment with radiotherapy, chemotherapy, and/or immunotherapy for malignant or autoimmune diseases
• Prior thalidomide therapy is allowed, however, patients must not have prior >= grade-3 allergic reactions to thalidomide
• Patients must not have prior history of desquamating rash from thalidomide at time of study entry
• Patients must not have clinically significant anemia resulting from iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis, or gastrointestinal bleeding
• Patients must not have used cytotoxic chemotherapeutic agents or experimental agents (agents that are not commercially available) for the treatment of MDS within 8 weeks of randomization
• Patients must not have prior history of malignancy other than MDS (except basal cell or squamous skin cell carcinoma or carcinoma in situ of the cervix or breast) unless the subject has been confirmed free of disease for >= 3 years
• Patients must not have any serious medical condition or any other unstable medical co-morbidity, or psychiatric illness that will prevent the subject from signing the informed consent form or will place the subject at unacceptable risk if he/she participates in the study
• Patients must not have a history of thrombo-embolic events within 3 years prior to study randomization
• Patients must not have known human immunodeficiency virus (HIV)-1 seropositivity because HIV can be an alternate cause of anemia.
• Patients must not have a known allergic reaction to epoetin alfa (Procrit) or human serum albumin
• Exclusion criteria for crossover registration from Arm A (lenalidomide alone) to Arm B

(lenalidomide and epoetin alfa):

• Patients must not have a limiting unresolved grade 3 or greater toxicity from lenalidomide monotherapy or drug intolerance preventing continuation of lenalidomide treatment

Related Conditions & MeSH terms

• Anemia
• Chronic Myelomonocytic Leukemia
• de Novo Myelodysplastic Syndrome
• Leukemia, Myelomonocytic, Chronic
• Leukemia, Myelomonocytic, Juvenile
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Procedure:
• Bone Marrow Biopsy
Undergo bone marrow biopsy

Biological:
• Epoetin Alfa
Given SC

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Lenalidomide
Given PO

Locations

Country	Name	City	State
United States	Jefferson Abington Hospital	Abington	Pennsylvania
United States	Bixby Medical Center	Adrian	Michigan
United States	Hickman Cancer Center	Adrian	Michigan
United States	Medini, Eitan MD (UIA Investigator)	Alexandria	Minnesota
United States	The Don and Sybil Harrington Cancer Center	Amarillo	Texas
United States	McFarland Clinic - Ames	Ames	Iowa
United States	Kaiser Permanente-Anaheim	Anaheim	California
United States	Alaska Breast Care and Surgery LLC	Anchorage	Alaska
United States	Alaska Women's Cancer Care	Anchorage	Alaska
United States	Anchorage Oncology Centre	Anchorage	Alaska
United States	Katmai Oncology Group	Anchorage	Alaska
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan
United States	Trinity Health Saint Joseph Mercy Hospital Ann Arbor	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	ThedaCare Regional Cancer Center	Appleton	Wisconsin
United States	Mission Hospital	Asheville	North Carolina
United States	King's Daughter's Medical Center	Ashland	Kentucky
United States	Augusta University Medical Center	Augusta	Georgia
United States	The Medical Center of Aurora	Aurora	Colorado
United States	Kaiser Permanente-Baldwin Park	Baldwin Park	California
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	Saint Agnes Hospital	Baltimore	Maryland
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Flaget Memorial Hospital	Bardstown	Kentucky
United States	Franciscan Saint Francis Health-Beech Grove	Beech Grove	Indiana
United States	Kaiser Permanente-Bellflower	Bellflower	California
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Walter Reed National Military Medical Center	Bethesda	Maryland
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Montana Cancer Consortium NCORP	Billings	Montana
United States	Northern Rockies Radiation Oncology 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	Mid Dakota Clinic	Bismarck	North Dakota
United States	Saint Alexius Medical Center	Bismarck	North Dakota
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
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	Boulder Community Hospital	Boulder	Colorado
United States	Toledo Clinic Cancer Centers-Bowling Green	Bowling Green	Ohio
United States	Bozeman Health Deaconess Hospital	Bozeman	Montana
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Steward Saint Elizabeth's Medical Center	Brighton	Massachusetts
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Montefiore Medical Center-Weiler Hospital	Bronx	New York
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Butler Memorial Hospital	Butler	Pennsylvania
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Aultman Health Foundation	Canton	Ohio
United States	Cleveland Clinic Mercy Hospital	Canton	Ohio
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	Carlisle Regional Cancer Center	Carlisle	Pennsylvania
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Rocky Mountain Oncology	Casper	Wyoming
United States	Mercy Hospital	Cedar Rapids	Iowa
United States	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa
United States	West Virginia University Charleston Division	Charleston	West Virginia
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	Hematology and Oncology Associates	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	Presence Resurrection Medical Center	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Weiss Memorial Hospital	Chicago	Illinois
United States	Marshfield Clinic-Chippewa Center	Chippewa Falls	Wisconsin
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Anderson	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Westside	Cincinnati	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Case Western Reserve University	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Southeastern Medical Oncology Center-Clinton	Clinton	North Carolina
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Mission Cancer and Blood - West Des Moines	Clive	Iowa
United States	North Coast Cancer Care-Clyde	Clyde	Ohio
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado
United States	MU Health - University Hospital/Ellis Fischel Cancer Center	Columbia	Missouri
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Bay Area Hospital	Coos Bay	Oregon
United States	Carle at The Riverfront	Danville	Illinois
United States	Danville Regional Medical Center	Danville	Virginia
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Dayton NCI Community Oncology Research Program	Dayton	Ohio
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Grandview Hospital	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	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	Porter Adventist Hospital	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	Western States Cancer Research NCORP	Denver	Colorado
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Iowa-Wide Oncology Research Coalition NCORP	Des Moines	Iowa
United States	Mercy Capitol	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Laurel	Des Moines	Iowa
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	Essentia Health Cancer Center	Duluth	Minnesota
United States	Mercy Medical Center	Durango	Colorado
United States	Prisma Health Cancer Institute - Easley	Easley	South Carolina
United States	Veterans Adminstration New Jersey Health Care System	East Orange	New Jersey
United States	Hematology Oncology Associates of Central New York-East Syracuse	East Syracuse	New York
United States	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Swedish Cancer Institute-Edmonds	Edmonds	Washington
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Elkhart Clinic	Elkhart	Indiana
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Michiana Hematology Oncology PC-Elkhart	Elkhart	Indiana
United States	Christiana Care - Union Hospital	Elkton	Maryland
United States	Elmhurst Memorial Hospital	Elmhurst	Illinois
United States	Hematology Oncology Center Incorporated	Elyria	Ohio
United States	Mercy Cancer Center-Elyria	Elyria	Ohio
United States	Mountain Blue Cancer Care Center - Swedish	Englewood	Colorado
United States	Swedish Medical Center	Englewood	Colorado
United States	Ephrata Cancer Center	Ephrata	Pennsylvania
United States	Ephrata Community Hospital	Ephrata	Pennsylvania
United States	OSF Saint Francis Hospital and Medical Group	Escanaba	Michigan
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Saint Francis Hospital	Evanston	Illinois
United States	Fairbanks Memorial Hospital	Fairbanks	Alaska
United States	University of Connecticut	Farmington	Connecticut
United States	Lake Region Healthcare Corporation-Cancer Care	Fergus Falls	Minnesota
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Kaiser Permanente-Fontana	Fontana	California
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Frederick Memorial Hospital	Frederick	Maryland
United States	Fredericksburg Oncology Inc	Fredericksburg	Virginia
United States	Unity Hospital	Fridley	Minnesota
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Aurora Health Care Germantown Health Center	Germantown	Wisconsin
United States	Adams Cancer Center	Gettysburg	Pennsylvania
United States	Glens Falls Hospital	Glens Falls	New York
United States	NorthShore University HealthSystem-Glenbrook Hospital	Glenview	Illinois
United States	Mountain Blue Cancer Care Center	Golden	Colorado
United States	Southeastern Medical Oncology Center-Goldsboro	Goldsboro	North Carolina
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	Aurora Cancer Care-Grafton	Grafton	Wisconsin
United States	Nebraska Cancer Specialists/Oncology Hematology West PC	Grand Island	Nebraska
United States	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado
United States	Benefis Sletten Cancer Institute	Great Falls	Montana
United States	Berdeaux, Donald MD (UIA Investigator)	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	Banner North Colorado Medical Center	Greeley	Colorado
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
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	Marin Cancer Care Inc	Greenbrae	California
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 Hospital	Greenville	South Carolina
United States	Wayne Hospital	Greenville	Ohio
United States	Self Regional Healthcare	Greenwood	South Carolina
United States	Rocky Mountain Cancer Centers-Greenwood Village	Greenwood Village	Colorado
United States	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	WellSpan Medical Oncology and Hematology	Hanover	Pennsylvania
United States	Kaiser Permanente - Harbor City	Harbor City	California
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	Northern Montana Hospital	Havre	Montana
United States	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania
United States	Saint Peter's Community Hospital	Helena	Montana
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	Memorial Regional Hospital/Joe DiMaggio Children's Hospital	Hollywood	Florida
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	IU Health Central Indiana Cancer Centers-East	Indianapolis	Indiana
United States	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan
United States	Kaiser Permanente-Irvine	Irvine	California
United States	Allegiance Health	Jackson	Michigan
United States	Baptist MD Anderson Cancer Center	Jacksonville	Florida
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Southeastern Medical Oncology Center-Jacksonville	Jacksonville	North Carolina
United States	Mercyhealth Hospital and Cancer Center - Janesville	Janesville	Wisconsin
United States	MU Health Care Goldschmidt Cancer Center	Jefferson City	Missouri
United States	University of Wisconsin Carbone Cancer Center Johnson Creek	Johnson Creek	Wisconsin
United States	Duly Health and Care Joliet	Joliet	Illinois
United States	Midwest Center for Hematology Oncology	Joliet	Illinois
United States	Jupiter Medical Center	Jupiter	Florida
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Glacier Oncology PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology	Kalispell	Montana
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	Kansas City Veterans Affairs Medical Center	Kansas City	Missouri
United States	North Kansas City Hospital	Kansas City	Missouri
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Joseph Health Center	Kansas City	Missouri
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	University Health Truman Medical Center	Kansas City	Missouri
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Cheshire Medical Center-Dartmouth-Hitchcock Keene	Keene	New Hampshire
United States	Keesler Medical Center	Keesler Air Force Base	Mississippi
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin
United States	Kettering Medical Center	Kettering	Ohio
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	EvergreenHealth Medical Center	Kirkland	Washington
United States	Thompson Cancer Survival Center	Knoxville	Tennessee
United States	Community Howard Regional Health	Kokomo	Indiana
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	IU Health La Porte Hospital	La Porte	Indiana
United States	IU Health Arnett Cancer Care	Lafayette	Indiana
United States	Rocky Mountain Cancer Centers-Lakewood	Lakewood	Colorado
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	University of Michigan Health - Sparrow Lansing	Lansing	Michigan
United States	Nevada Cancer Research Foundation NCORP	Las Vegas	Nevada
United States	OptumCare Cancer Care at Fort Apache	Las Vegas	Nevada
United States	Summerlin Hospital Medical Center	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri
United States	Leesburg Regional Medical Center	Leesburg	Florida
United States	Beebe Medical Center	Lewes	Delaware
United States	Lewistown Hospital	Lewistown	Pennsylvania
United States	Liberty Radiation Oncology Center	Liberty	Missouri
United States	AMG Libertyville - Oncology	Libertyville	Illinois
United States	Lima Memorial Hospital	Lima	Ohio
United States	Saint Rita's Medical Center	Lima	Ohio
United States	Nebraska Cancer Research Center	Lincoln	Nebraska
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	Rocky Mountain Cancer Centers-Sky Ridge	Lone Tree	Colorado
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Longmont United Hospital	Longmont	Colorado
United States	PeaceHealth Saint John Medical Center	Longview	Washington
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Kaiser Permanente West Los Angeles	Los Angeles	California
United States	Jewish Hospital	Louisville	Kentucky
United States	UofL Health Medical Center Northeast	Louisville	Kentucky
United States	Banner McKee Medical Center	Loveland	Colorado
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	SSM Health Dean Medical Group - South Madison Campus	Madison	Wisconsin
United States	University of Wisconsin Carbone Cancer Center - University Hospital	Madison	Wisconsin
United States	Holy Family Memorial Hospital	Manitowoc	Wisconsin
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Aurora Bay Area Medical Group-Marinette	Marinette	Wisconsin
United States	Bay Area Medical Center	Marinette	Wisconsin
United States	UP Health System Marquette	Marquette	Michigan
United States	Marshfield Medical Center	Marshfield	Wisconsin
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Sovah Health Martinsville	Martinsville	Virginia
United States	Fremont - Rideout Cancer Center	Marysville	California
United States	Mercy Medical Center - North Iowa	Mason City	Iowa
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Saint Luke's Hospital	Maumee	Ohio
United States	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio
United States	Toledo Radiation Oncology at Northwest Ohio Onocolgy Center	Maumee	Ohio
United States	Riddle Memorial Hospital	Media	Pennsylvania
United States	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	Premier Oncology Hematology Associates	Merrillville	Indiana
United States	Holy Family Hospital	Methuen	Massachusetts
United States	Miami Cancer Institute	Miami	Florida
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Garnet Health Medical Center	Middletown	New York
United States	Aurora Cancer Care-Milwaukee	Milwaukee	Wisconsin
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Aurora Sinai Medical Center	Milwaukee	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	NYU Langone Hospital - Long Island	Mineola	New York
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Health Partners Inc	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Minneapolis VA Medical Center	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Memorial Regional Cancer Center Day Road	Mishawaka	Indiana
United States	Michiana Hematology Oncology PC-Mishawaka	Mishawaka	Indiana
United States	Saint Joseph Regional Medical Center-Mishawaka	Mishawaka	Indiana
United States	Community Medical Center	Missoula	Montana
United States	Guardian Oncology and Center for Wellness	Missoula	Montana
United States	Montana Cancer Specialists	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Mercy Memorial Hospital	Monroe	Michigan
United States	Toledo Clinic Cancer Centers-Monroe	Monroe	Michigan
United States	West Virginia University Healthcare	Morgantown	West Virginia
United States	Virtua Memorial	Mount Holly	New Jersey
United States	Skagit Valley Hospital	Mount Vernon	Washington
United States	ProHealth D N Greenwald Center	Mukwonago	Wisconsin
United States	Inspira Medical Center Mullica Hill	Mullica Hill	New Jersey
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	Jersey Shore Medical Center	Neptune	New Jersey
United States	The Hospital of Central Connecticut	New Britain	Connecticut
United States	Yale University	New Haven	Connecticut
United States	Cancer Center of Western Wisconsin	New Richmond	Wisconsin
United States	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Medical Oncology Hematology Consultants PA	Newark	Delaware
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Corewell Health Lakeland Hospitals - Niles Hospital	Niles	Michigan
United States	Illinois Cancer Specialists-Niles	Niles	Illinois
United States	Fisher-Titus Medical Center	Norwalk	Ohio
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Oconto Falls	Oconto Falls	Wisconsin
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Alegent Health Immanuel Medical Center	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
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	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Ottumwa Regional Health Center	Ottumwa	Iowa
United States	Menorah Medical Center	Overland Park	Kansas
United States	Saint Luke's South Hospital	Overland Park	Kansas
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	Kaiser Permanente - Panorama City	Panorama City	California
United States	Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Parker Adventist Hospital	Parker	Colorado
United States	Rocky Mountain Cancer Centers-Parker	Parker	Colorado
United States	Camden Clark Medical Center	Parkersburg	West Virginia
United States	Singing River Hospital	Pascagoula	Mississippi
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Phoenixville Hospital	Phoenixville	Pennsylvania
United States	Michiana Hematology Oncology PC-Plymouth	Plymouth	Indiana
United States	Trinity Health Saint Joseph Mercy Oakland Hospital	Pontiac	Michigan
United States	Lake Huron Medical Center	Port Huron	Michigan
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	Pottstown Hospital	Pottstown	Pennsylvania
United States	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington
United States	Kansas City NCI Community Oncology Research Program	Prairie Village	Kansas
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Princeton Community Hospital	Princeton	West Virginia
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	Aurora Cancer Care-Racine	Racine	Wisconsin
United States	UNC Rex Cancer Center of Wakefield	Raleigh	North Carolina
United States	UNC Rex Healthcare	Raleigh	North Carolina
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Penn State Health Saint Joseph Medical Center	Reading	Pennsylvania
United States	Riverview Medical Center/Booker Cancer Center	Red Bank	New Jersey
United States	Beebe Health Campus	Rehoboth Beach	Delaware
United States	Ascension Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	Reid Health	Richmond	Indiana
United States	Kaiser Permanente-Riverside	Riverside	California
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Highland Hospital	Rochester	New York
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	Swedish American Hospital	Rockford	Illinois
United States	UW Health Carbone Cancer Center Rockford	Rockford	Illinois
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
United States	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota
United States	Saint Cloud Hospital	Saint Cloud	Minnesota
United States	Saint Helena Hospital	Saint Helena	California
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	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Saint Joseph Oncology Inc	Saint Joseph	Missouri
United States	Center for Cancer Care and Research	Saint Louis	Missouri
United States	Comprehensive Cancer Care PC	Saint Louis	Missouri
United States	Mercy Hospital South	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Kaiser Permanente-San Diego Mission	San Diego	California
United States	Kaiser Permanente-San Diego Zion	San Diego	California
United States	Kaiser Permanente-San Marcos	San Marcos	California
United States	North Coast Cancer Care	Sandusky	Ohio
United States	Guthrie Medical Group PC-Robert Packer Hospital	Sayre	Pennsylvania
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	TidalHealth Nanticoke / Allen Cancer Center	Seaford	Delaware
United States	Kaiser Permanente Washington	Seattle	Washington
United States	Minor and James Medical PLLC	Seattle	Washington
United States	Pacific Medical Center-First Hill	Seattle	Washington
United States	Swedish Medical Center-Ballard Campus	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	University of Washington Medical Center - Montlake	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Advent Health - Shawnee Mission Medical Center	Shawnee Mission	Kansas
United States	HSHS Saint Nicholas Hospital	Sheboygan	Wisconsin
United States	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Mercy Medical Center-Sioux City	Sioux City	Iowa
United States	Saint Luke's Regional Medical Center	Sioux City	Iowa
United States	Siouxland Regional Cancer Center	Sioux City	Iowa
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Avera McKennan Hospital and University Health Center	Sioux Falls	South Dakota
United States	Hematology Oncology Associates of Illinois - Skokie	Skokie	Illinois
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Michiana Hematology Oncology PC-South Bend	South Bend	Indiana
United States	Northern Indiana Cancer Research Consortium	South Bend	Indiana
United States	South Bend Clinic	South Bend	Indiana
United States	Ascension Providence Hospitals - Southfield	Southfield	Michigan
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	Evergreen Hematology and Oncology PS	Spokane	Washington
United States	Central Illinois Hematology Oncology Center	Springfield	Illinois
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	Geisinger Medical Group	State College	Pennsylvania
United States	Mount Nittany Medical Center	State College	Pennsylvania
United States	Iredell Memorial Hospital	Statesville	North Carolina
United States	Ascension Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Lakeview Hospital	Stillwater	Minnesota
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	Aurora Medical Center in Summit	Summit	Wisconsin
United States	ProMedica Flower Hospital	Sylvania	Ohio
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	Moffitt Cancer Center	Tampa	Florida
United States	North Suburban Medical Center	Thornton	Colorado
United States	Mercy Hospital of Tiffin	Tiffin	Ohio
United States	Mercy Health - Saint Anne Hospital	Toledo	Ohio
United States	Mercy Health - Saint Vincent Hospital	Toledo	Ohio
United States	ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital	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	Community Medical Center	Toms River	New Jersey
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	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin
United States	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Inspira Medical Center Vineland	Vineland	New Jersey
United States	Virtua Voorhees	Voorhees	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	Aurora Cancer Care-Waukesha	Waukesha	Wisconsin
United States	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin
United States	Aspirus Regional Cancer Center	Wausau	Wisconsin
United States	Fulton County Health Center	Wauseon	Ohio
United States	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin
United States	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington
United States	Aurora West Allis Medical Center	West Allis	Wisconsin
United States	Chester County Hospital	West Chester	Pennsylvania
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Reading Hospital	West Reading	Pennsylvania
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	Michiana Hematology Oncology PC-Westville	Westville	Indiana
United States	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado
United States	Presbyterian Intercommunity Hospital	Whittier	California
United States	Wesley Medical Center	Wichita	Kansas
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	UPMC Susquehanna	Williamsport	Pennsylvania
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Clinton Memorial Hospital/Foster J Boyd Regional Cancer Center	Wilmington	Ohio
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Aspirus Cancer Care - Wisconsin Rapids	Wisconsin Rapids	Wisconsin
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Kaiser Permanente-Woodland Hills	Woodland Hills	California
United States	UMass Memorial Medical Center - University Campus	Worcester	Massachusetts
United States	Lankenau Medical Center	Wynnewood	Pennsylvania
United States	Greene Memorial Hospital	Xenia	Ohio
United States	WellSpan Health-York Hospital	York	Pennsylvania

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
Other	The Association Between CD45 Isoform Profile and ex Vivo Augmentation of STAT5 Phosphorylation by Lenalidomide	To evaluate the effect of CD45 isoform profile on lenalidomide enhancement of erythropoietin-induced STAT5 phosphorylation in CD71Hi erythroid precursors and the relationship to erythroid response.	Assessed at baseline and after completion of 16 weeks of treatment
Other	RNA and Protein Expression Level of Cdc25C, PP2A and Their Phosphatase Substrates, Cdc2phospho-Tyr15 and Cdc25Cphospho-Ser216	To characterize molecular targets relevant to lenalidomide cytotoxicity in del5q31.1 cells.	Assessed at baseline and after completion of 16 weeks of treatment
Other	Proportion of Patients With Cryptic Chromosome 5q31.1 Deletions	To evaluate the frequency of cryptic chromosome 5q31.1 deletions in patients with non-del5q31.1 MDS by array based genomic scan, and to determine the relationship to hematologic response.	Assessed at baseline and after completion of 16 weeks of treatment
Primary	Proportion of Patients With Major Erythroid Response (MER)	Major erythroid response is defined as transfusion-independence for = 8 consecutive weeks for patients who were red blood cell transfusion-dependent at baseline AND a = 1 g/dL hemoglobin rise compared to mean pre-transfusion baseline value; or a > 2 g/dL rise in hemoglobin without transfusion for non-transfusion dependent patients.	Assessed after completion of 16 weeks of treatment
Secondary	Time to Major Erythroid Response (MER)	Time to major erythroid response (MER) is defined in responders as the time from randomization to the documented date of MER.; For transfusion independent patients, the date of MER is the first date of the elevation in hemoglobin level of more than 2 g/dL that has been sustained for at least 8 weeks. For transfusion dependent patients, the date of MER is the beginning date of the time interval of transfusion independence that has been sustained for at least eight weeks.	Assessed every cycle during treatment and then 3 and 6 months after last protocol treatment
Secondary	Duration of Major Erythroid Response (MER)	Duration of major erythroid response (MER) is defined as the time interval between the documented date of MER and the earliest date of resumption of red blood cell transfusions = 2 units in an 8-week period, a reduction in hemoglobin concentration = 2 g/dL in the absence of acute infection, gastrointestinal bleeding and hemolysis, or death.	Assessed every cycle during treatment and then 3 and 6 months after last protocol treatment
Secondary	Proportion of Patients With Major Erythroid Response (MER) to Salvage Combination Therapy	Major erythroid response is defined as transfusion-independence for = 8 consecutive weeks for patients who were red blood cell transfusion-dependent at baseline AND a = 1 g/dL hemoglobin rise compared to mean pre-transfusion baseline value; or a > 2 g/dL rise in hemoglobin without transfusion for non-transfusion dependent patients.	Assessed after completion of 16 weeks of treatment
Secondary	Proportion of Patients With Minor Erythroid Response	The definition of minor erythroid response: the mean hemoglobin is sustained 1.0 to 2.0 g/dL above the baseline value for a minimum of 8 weeks; or a 50% or greater decrease in 8-week red blood cell transfusion requirements compared to baseline.	Assessed every cycle during treatment and after completion of 16 weeks of treatment
Secondary	Proportion of Patients With Major Erythroid Response (MER) Among Those With Chromosome 5q31.1 Deletion	Major erythroid response is defined as transfusion-independence for = 8 consecutive weeks for patients who were red blood cell transfusion-dependent at baseline AND a = 1 g/dL hemoglobin rise compared to mean pre-transfusion baseline value; or a > 2 g/dL rise in hemoglobin without transfusion for non-transfusion dependent patients.	Assessed after completion of 16 weeks of treatment
Secondary	Proportion of Patients With Bone Marrow Response	Bone marrow response includes complete remission (CR) and partial remission (PR).; Complete remission (CR): Bone marrow showing < 5% myeloblasts with normal maturation of all cell lines, with no evidence for dysplasia. When erythroid precursors constitute < 50% of bone marrow nucleated cells, the percent of blasts is based on all nucleated cells; when there are = 50% erythroid cells, the percent blasts should be based on the non-erythroid cells.; Partial remission (PR): All of the CR criteria (if abnormal prior to treatment), except blasts decreased by 50% over pre-treatment, or a less advanced Myelodysplastic Syndromes (MDS) World Health Organization (WHO) classification than pretreatment. Cellularity and morphology are not relevant.	Assessed at 16 weeks
Secondary	Proportion of Patients With Cytogenetic Response	Evaluation of cytogenetic response requires 20 analyzable metaphases when using conventional techniques. Analysis of data will require 20 metaphases before and after treatment, which must be done on bone marrow only (peripheral blood is not a substitute). Fluorescent in situ hybridization (FISH) may be used as a supplement to follow a specifically defined cytogenetic abnormality, but it is not a substitute for conventional cytogenetic studies. Cytogenetic response is defined as follows: Complete response: Restoration of a normal karyotype in patients with a documented pre-existing clonal (>2 metaphases abnormal) chromosome abnormalities.; Partial response: > 50% reduction in the percentage of bone marrow metaphases with only clonal abnormality.	Assessed at baseline and after completion of 16 weeks of treatment
Secondary	Association Between Major Erythroid Response and Cytogenetic Response	Major erythroid response is defined as transfusion-independence for = 8 consecutive weeks for patients who were red blood cell transfusion-dependent at baseline AND a = 1 g/dL hemoglobin rise compared to mean pre-transfusion baseline value; or a > 2 g/dL rise in hemoglobin without transfusion for non-transfusion dependent patients.; Evaluation of cytogenetic response requires 20 analyzable metaphases before and after treatment, which must be done on bone marrow only. Fluorescent in situ hybridization (FISH) may be used as a supplement to follow a specifically defined cytogenetic abnormality, but it is not a substitute for conventional cytogenetic studies. Cytogenetic response is defined as follows: Complete response: Restoration of a normal karyotype in patients with a documented pre-existing clonal (>2 metaphases abnormal) chromosome abnormalities.; Partial response: > 50% reduction in the percentage of bone marrow metaphases with only clonal abnormality.	Assessed at baseline and after completion of 16 weeks of treatment
Secondary	Pretreatment Endogenous Erythropoietin Level	Pretreatment endogenous erythropoietin level was assessed at baseline. The association between pretreatment endogenous erythropoietin level and major erythroid response was evaluated among patients who received lenalidomide alone.; Major erythroid response is defined as transfusion-independence for = 8 consecutive weeks for patients who were red blood cell transfusion-dependent at baseline AND a = 1 g/dL hemoglobin rise compared to mean pre-transfusion baseline value; or a > 2 g/dL rise in hemoglobin without transfusion for non-transfusion dependent patients.	Assessed at baseline and after completion of 16 weeks of treatment