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

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Active, not recruiting
CT.gov ID
NCT00843882
Collaborator
(none)
247
Enrollment
513
Locations
2
Arms
0.5
Patients Per Site

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

PRIMARY OBJECTIVE:
  1. 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:

  1. 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.

  2. To evaluate and compare the frequency of minor erythroid response by treatment assignment.

  3. To investigate the mechanism and target of lenalidomide action in patients with chromosome 5q31.1 deletion.

  4. To evaluate the frequency of cytogenetic response and progression, and the relationship between cytogenetic pattern and erythroid response.

  5. To evaluate the frequency of bone marrow response (complete response [CR] + partial response [PR]).

  6. 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.

ARM B: Patients receive lenalidomide PO QD on days 1-21 and epoetin alfa subcutaneously (SC) once weekly.

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
247 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jan 29, 2009
Actual Primary Completion Date :
Jul 8, 2019

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Arm A (lenalidomide)

Patients receive lenalidomide PO QD on days 1-21.

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Lenalidomide
Given PO
Other Names:
  • CC-5013
  • CC5013
  • CDC 501
  • Revlimid

    		•
    Experimental: Arm B (lenalidomide, epoetin alfa)

    Patients receive lenalidomide PO QD on days 1-21 and epoetin alfa SC once weekly.

    Biological: Epoetin Alfa
    Given SC
    Other Names:
  • EPO
  • Epoetin alfa-epbx
  • Epogen
  • Eprex
  • Procrit
  • Retacrit

    • Other: Laboratory Biomarker Analysis
    Correlative studies

    Drug: Lenalidomide
    Given PO
    Other Names:
  • CC-5013
  • CC5013
  • CDC 501
  • Revlimid

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Proportion of Patients With Major Erythroid Response (MER) [Assessed after completion of 16 weeks of treatment]

      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.

    Secondary Outcome Measures

    1. Time to Major Erythroid Response (MER) [Assessed every cycle during treatment and then 3 and 6 months after last protocol treatment]

      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.

    2. Duration of Major Erythroid Response (MER) [Assessed every cycle during treatment and then 3 and 6 months after last protocol treatment]

      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.

    3. Proportion of Patients With Major Erythroid Response (MER) to Salvage Combination Therapy [Assessed after completion of 16 weeks of treatment]

      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.

    4. Proportion of Patients With Minor Erythroid Response [Assessed every cycle during treatment and after completion of 16 weeks of treatment]

      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.

    5. Proportion of Patients With Major Erythroid Response (MER) Among Those With Chromosome 5q31.1 Deletion [Assessed after completion of 16 weeks of treatment]

      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.

    6. Proportion of Patients With Bone Marrow Response [Assessed at 16 weeks]

      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.

    7. Proportion of Patients With Cytogenetic Response [Assessed at baseline and after completion of 16 weeks of treatment]

      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.

    8. Association Between Major Erythroid Response and Cytogenetic Response [Assessed at baseline and after completion of 16 weeks of treatment]

      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.

    9. Pretreatment Endogenous Erythropoietin Level [Assessed at baseline and after completion of 16 weeks of treatment]

      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.

    Other Outcome Measures

    1. The Association Between CD45 Isoform Profile and ex Vivo Augmentation of STAT5 Phosphorylation by Lenalidomide [Assessed at baseline and after completion of 16 weeks of treatment]

      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.

    2. RNA and Protein Expression Level of Cdc25C, PP2A and Their Phosphatase Substrates, Cdc2phospho-Tyr15 and Cdc25Cphospho-Ser216 [Assessed at baseline and after completion of 16 weeks of treatment]

      To characterize molecular targets relevant to lenalidomide cytotoxicity in del5q31.1 cells.

    3. Proportion of Patients With Cryptic Chromosome 5q31.1 Deletions [Assessed at baseline and after completion of 16 weeks of treatment]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • 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 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

    • 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)

    • 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

    • 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

    • 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)

    • Prior thalidomide 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

    • Eligibility 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

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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama at Birmingham Cancer Center Birmingham Alabama United States 35233
    2 Alaska Breast Care and Surgery LLC Anchorage Alaska United States 99508
    3 Alaska Women's Cancer Care Anchorage Alaska United States 99508
    4 Anchorage Oncology Centre Anchorage Alaska United States 99508
    5 Katmai Oncology Group Anchorage Alaska United States 99508
    6 Providence Alaska Medical Center Anchorage Alaska United States 99508
    7 Fairbanks Memorial Hospital Fairbanks Alaska United States 99701
    8 Mayo Clinic in Arizona Scottsdale Arizona United States 85259
    9 Banner University Medical Center - Tucson Tucson Arizona United States 85719
    10 University of Arizona Cancer Center-North Campus Tucson Arizona United States 85719
    11 Kaiser Permanente-Anaheim Anaheim California United States 92806
    12 Kaiser Permanente-Baldwin Park Baldwin Park California United States 91706
    13 Kaiser Permanente-Bellflower Bellflower California United States 90706
    14 Providence Saint Joseph Medical Center/Disney Family Cancer Center Burbank California United States 91505
    15 Kaiser Permanente-Fontana Fontana California United States 92335
    16 Marin Cancer Care Inc Greenbrae California United States 94904
    17 Kaiser Permanente - Harbor City Harbor City California United States 90710
    18 Kaiser Permanente-Irvine Irvine California United States 92618
    19 Kaiser Permanente Los Angeles Medical Center Los Angeles California United States 90027
    20 Kaiser Permanente West Los Angeles Los Angeles California United States 90034
    21 Fremont - Rideout Cancer Center Marysville California United States 95901
    22 Stanford Cancer Institute Palo Alto Palo Alto California United States 94304
    23 Kaiser Permanente - Panorama City Panorama City California United States 91402
    24 Kaiser Permanente-Riverside Riverside California United States 92505
    25 University of California Davis Comprehensive Cancer Center Sacramento California United States 95817
    26 Saint Helena Hospital Saint Helena California United States 94574
    27 Kaiser Permanente-San Diego Mission San Diego California United States 92108
    28 Kaiser Permanente-San Diego Zion San Diego California United States 92120
    29 Kaiser Permanente-San Marcos San Marcos California United States 92078
    30 Presbyterian Intercommunity Hospital Whittier California United States 90602
    31 Kaiser Permanente-Woodland Hills Woodland Hills California United States 91367
    32 The Medical Center of Aurora Aurora Colorado United States 80012
    33 Boulder Community Hospital Boulder Colorado United States 80301
    34 Penrose-Saint Francis Healthcare Colorado Springs Colorado United States 80907
    35 Rocky Mountain Cancer Centers-Penrose Colorado Springs Colorado United States 80907
    36 Porter Adventist Hospital Denver Colorado United States 80210
    37 Colorado Blood Cancer Institute Denver Colorado United States 80218
    38 Presbyterian - Saint Lukes Medical Center - Health One Denver Colorado United States 80218
    39 Rocky Mountain Cancer Centers-Midtown Denver Colorado United States 80218
    40 SCL Health Saint Joseph Hospital Denver Colorado United States 80218
    41 Rocky Mountain Cancer Centers-Rose Denver Colorado United States 80220
    42 Rose Medical Center Denver Colorado United States 80220
    43 Western States Cancer Research NCORP Denver Colorado United States 80222
    44 Mercy Medical Center Durango Colorado United States 81301
    45 Mountain Blue Cancer Care Center - Swedish Englewood Colorado United States 80113
    46 Swedish Medical Center Englewood Colorado United States 80113
    47 Poudre Valley Hospital Fort Collins Colorado United States 80524
    48 Mountain Blue Cancer Care Center Golden Colorado United States 80401
    49 Saint Mary's Hospital and Regional Medical Center Grand Junction Colorado United States 81501
    50 North Colorado Medical Center Greeley Colorado United States 80631
    51 Rocky Mountain Cancer Centers-Greenwood Village Greenwood Village Colorado United States 80111
    52 Rocky Mountain Cancer Centers-Lakewood Lakewood Colorado United States 80228
    53 Saint Anthony Hospital Lakewood Colorado United States 80228
    54 Littleton Adventist Hospital Littleton Colorado United States 80122
    55 Rocky Mountain Cancer Centers-Sky Ridge Lone Tree Colorado United States 80124
    56 Sky Ridge Medical Center Lone Tree Colorado United States 80124
    57 Longmont United Hospital Longmont Colorado United States 80501
    58 McKee Medical Center Loveland Colorado United States 80539
    59 Parker Adventist Hospital Parker Colorado United States 80138
    60 Rocky Mountain Cancer Centers-Parker Parker Colorado United States 80138
    61 Saint Mary Corwin Medical Center Pueblo Colorado United States 81004
    62 North Suburban Medical Center Thornton Colorado United States 80229
    63 SCL Health Lutheran Medical Center Wheat Ridge Colorado United States 80033
    64 University of Connecticut Farmington Connecticut United States 06030
    65 Smilow Cancer Hospital Care Center at Saint Francis Hartford Connecticut United States 06105
    66 The Hospital of Central Connecticut New Britain Connecticut United States 06050
    67 Yale University New Haven Connecticut United States 06520
    68 Beebe Medical Center Lewes Delaware United States 19958
    69 Delaware Clinical and Laboratory Physicians PA Newark Delaware United States 19713
    70 Helen F Graham Cancer Center Newark Delaware United States 19713
    71 Medical Oncology Hematology Consultants PA Newark Delaware United States 19713
    72 Christiana Care Health System-Christiana Hospital Newark Delaware United States 19718
    73 Beebe Health Campus Rehoboth Beach Delaware United States 19971
    74 TidalHealth Nanticoke / Allen Cancer Center Seaford Delaware United States 19973
    75 Holy Cross Hospital Fort Lauderdale Florida United States 33308
    76 Memorial Regional Hospital/Joe DiMaggio Children's Hospital Hollywood Florida United States 33021
    77 Baptist MD Anderson Cancer Center Jacksonville Florida United States 32207
    78 Mayo Clinic in Florida Jacksonville Florida United States 32224-9980
    79 Jupiter Medical Center Jupiter Florida United States 33458
    80 Leesburg Regional Medical Center Leesburg Florida United States 34748
    81 Mount Sinai Medical Center Miami Beach Florida United States 33140
    82 University of Miami Miller School of Medicine-Sylvester Cancer Center Miami Florida United States 33136
    83 Miami Cancer Institute Miami Florida United States 33176
    84 Moffitt Cancer Center Tampa Florida United States 33612
    85 Augusta University Medical Center Augusta Georgia United States 30912
    86 Saint Alphonsus Cancer Care Center-Boise Boise Idaho United States 83706
    87 Saint Luke's Cancer Institute - Boise Boise Idaho United States 83712
    88 Saint Luke's Cancer Institute - Fruitland Fruitland Idaho United States 83619
    89 Saint Luke's Cancer Institute - Meridian Meridian Idaho United States 83642
    90 Saint Luke's Cancer Institute - Nampa Nampa Idaho United States 83686
    91 Kootenai Clinic Cancer Services - Post Falls Post Falls Idaho United States 83854
    92 Saint Luke's Cancer Institute - Twin Falls Twin Falls Idaho United States 83301
    93 Illinois CancerCare-Bloomington Bloomington Illinois United States 61704
    94 Illinois CancerCare-Canton Canton Illinois United States 61520
    95 Illinois CancerCare-Carthage Carthage Illinois United States 62321
    96 Hematology and Oncology Associates Chicago Illinois United States 60611
    97 Northwestern University Chicago Illinois United States 60611
    98 Presence Resurrection Medical Center Chicago Illinois United States 60631
    99 University of Chicago Comprehensive Cancer Center Chicago Illinois United States 60637
    100 Weiss Memorial Hospital Chicago Illinois United States 60640
    101 Carle on Vermilion Danville Illinois United States 61832
    102 Cancer Care Specialists of Illinois - Decatur Decatur Illinois United States 62526
    103 Decatur Memorial Hospital Decatur Illinois United States 62526
    104 Carle Physician Group-Effingham Effingham Illinois United States 62401
    105 Crossroads Cancer Center Effingham Illinois United States 62401
    106 Elmhurst Memorial Hospital Elmhurst Illinois United States 60126
    107 Illinois CancerCare-Eureka Eureka Illinois United States 61530
    108 NorthShore University HealthSystem-Evanston Hospital Evanston Illinois United States 60201
    109 Saint Francis Hospital Evanston Illinois United States 60202
    110 Illinois CancerCare-Galesburg Galesburg Illinois United States 61401
    111 NorthShore University HealthSystem-Glenbrook Hospital Glenview Illinois United States 60026
    112 Hematology Oncology Associates of Illinois-Highland Park Highland Park Illinois United States 60035
    113 NorthShore University HealthSystem-Highland Park Hospital Highland Park Illinois United States 60035
    114 Midwest Center for Hematology Oncology Joliet Illinois United States 60432
    115 Duly Health and Care Joliet Joliet Illinois United States 60435
    116 Presence Saint Mary's Hospital Kankakee Illinois United States 60901
    117 Illinois CancerCare-Kewanee Clinic Kewanee Illinois United States 61443
    118 AMG Libertyville - Oncology Libertyville Illinois United States 60048
    119 Illinois CancerCare-Macomb Macomb Illinois United States 61455
    120 Carle Physician Group-Mattoon/Charleston Mattoon Illinois United States 61938
    121 Illinois Cancer Specialists-Niles Niles Illinois United States 60714
    122 Cancer Care Center of O'Fallon O'Fallon Illinois United States 62269
    123 Illinois CancerCare-Ottawa Clinic Ottawa Illinois United States 61350
    124 Illinois CancerCare-Pekin Pekin Illinois United States 61554
    125 Illinois CancerCare-Peoria Peoria Illinois United States 61615
    126 Illinois CancerCare-Peru Peru Illinois United States 61354
    127 Illinois CancerCare-Princeton Princeton Illinois United States 61356
    128 Swedish American Hospital Rockford Illinois United States 61104
    129 SwedishAmerican Regional Cancer Center/ACT Rockford Illinois United States 61114
    130 Hematology Oncology Associates of Illinois - Skokie Skokie Illinois United States 60076
    131 Central Illinois Hematology Oncology Center Springfield Illinois United States 62702
    132 Southern Illinois University School of Medicine Springfield Illinois United States 62702
    133 Springfield Clinic Springfield Illinois United States 62702
    134 Memorial Medical Center Springfield Illinois United States 62781
    135 Carle Cancer Center Urbana Illinois United States 61801
    136 The Carle Foundation Hospital Urbana Illinois United States 61801
    137 Northwestern Medicine Cancer Center Warrenville Warrenville Illinois United States 60555
    138 Franciscan Saint Francis Health-Beech Grove Beech Grove Indiana United States 46107
    139 Elkhart Clinic Elkhart Indiana United States 46514-2098
    140 Michiana Hematology Oncology PC-Elkhart Elkhart Indiana United States 46514
    141 Elkhart General Hospital Elkhart Indiana United States 46515
    142 Fort Wayne Medical Oncology and Hematology Inc-Parkview Fort Wayne Indiana United States 46845
    143 IU Health Central Indiana Cancer Centers-East Indianapolis Indiana United States 46219
    144 Community Howard Regional Health Kokomo Indiana United States 46904
    145 IU Health La Porte Hospital La Porte Indiana United States 46350
    146 IU Health Arnett Cancer Care Lafayette Indiana United States 47904
    147 Premier Oncology Hematology Associates Merrillville Indiana United States 46410
    148 Memorial Regional Cancer Center Day Road Mishawaka Indiana United States 46545
    149 Michiana Hematology Oncology PC-Mishawaka Mishawaka Indiana United States 46545
    150 Saint Joseph Regional Medical Center-Mishawaka Mishawaka Indiana United States 46545
    151 Michiana Hematology Oncology PC-Plymouth Plymouth Indiana United States 46563
    152 Reid Health Richmond Indiana United States 47374
    153 Memorial Hospital of South Bend South Bend Indiana United States 46601
    154 Michiana Hematology Oncology PC-South Bend South Bend Indiana United States 46601
    155 South Bend Clinic South Bend Indiana United States 46617
    156 Northern Indiana Cancer Research Consortium South Bend Indiana United States 46628
    157 Michiana Hematology Oncology PC-Westville Westville Indiana United States 46391
    158 McFarland Clinic PC - Ames Ames Iowa United States 50010
    159 Mercy Hospital Cedar Rapids Iowa United States 52403
    160 Oncology Associates at Mercy Medical Center Cedar Rapids Iowa United States 52403
    161 Medical Oncology and Hematology Associates-West Des Moines Clive Iowa United States 50325
    162 Mercy Cancer Center-West Lakes Clive Iowa United States 50325
    163 Mercy Capitol Des Moines Iowa United States 50307
    164 Iowa Methodist Medical Center Des Moines Iowa United States 50309
    165 Iowa-Wide Oncology Research Coalition NCORP Des Moines Iowa United States 50309
    166 Medical Oncology and Hematology Associates-Des Moines Des Moines Iowa United States 50309
    167 Medical Oncology and Hematology Associates-Laurel Des Moines Iowa United States 50314
    168 Mercy Medical Center - Des Moines Des Moines Iowa United States 50314
    169 Iowa Lutheran Hospital Des Moines Iowa United States 50316
    170 Mercy Medical Center - North Iowa Mason City Iowa United States 50401
    171 Ottumwa Regional Health Center Ottumwa Iowa United States 52501
    172 Siouxland Regional Cancer Center Sioux City Iowa United States 51101
    173 Mercy Medical Center-Sioux City Sioux City Iowa United States 51102
    174 Saint Luke's Regional Medical Center Sioux City Iowa United States 51104
    175 Mercy Medical Center-West Lakes West Des Moines Iowa United States 50266
    176 Lawrence Memorial Hospital Lawrence Kansas United States 66044
    177 Menorah Medical Center Overland Park Kansas United States 66209
    178 Saint Luke's South Hospital Overland Park Kansas United States 66213
    179 Kansas City NCI Community Oncology Research Program Prairie Village Kansas United States 66208
    180 Advent Health - Shawnee Mission Medical Center Shawnee Mission Kansas United States 66204
    181 Wesley Medical Center Wichita Kansas United States 67214
    182 King's Daughter's Medical Center Ashland Kentucky United States 41101
    183 Flaget Memorial Hospital Bardstown Kentucky United States 40004
    184 Jewish Hospital Louisville Kentucky United States 40202
    185 UofL Health Medical Center Northeast Louisville Kentucky United States 40245
    186 University of Maryland/Greenebaum Cancer Center Baltimore Maryland United States 21201
    187 Saint Agnes Hospital Baltimore Maryland United States 21229
    188 Johns Hopkins University/Sidney Kimmel Cancer Center Baltimore Maryland United States 21287
    189 Walter Reed National Military Medical Center Bethesda Maryland United States 20889-5600
    190 Christiana Care - Union Hospital Elkton Maryland United States 21921
    191 Frederick Memorial Hospital Frederick Maryland United States 21701
    192 Steward Saint Elizabeth's Medical Center Brighton Massachusetts United States 02135
    193 Lahey Hospital and Medical Center Burlington Massachusetts United States 01805
    194 Holy Family Hospital Methuen Massachusetts United States 01844
    195 UMass Memorial Medical Center - University Campus Worcester Massachusetts United States 01655
    196 Bixby Medical Center Adrian Michigan United States 49221
    197 Hickman Cancer Center Adrian Michigan United States 49221
    198 Michigan Cancer Research Consortium NCORP Ann Arbor Michigan United States 48106
    199 Saint Joseph Mercy Hospital Ann Arbor Michigan United States 48106
    200 University of Michigan Comprehensive Cancer Center Ann Arbor Michigan United States 48109
    201 Beaumont Hospital - Dearborn Dearborn Michigan United States 48124
    202 Wayne State University/Karmanos Cancer Institute Detroit Michigan United States 48201
    203 Henry Ford Hospital Detroit Michigan United States 48202
    204 Ascension Saint John Hospital Detroit Michigan United States 48236
    205 Green Bay Oncology - Escanaba Escanaba Michigan United States 49829
    206 Genesys Hurley Cancer Institute Flint Michigan United States 48503
    207 Hurley Medical Center Flint Michigan United States 48503
    208 Genesys Regional Medical Center-West Flint Campus Flint Michigan United States 48532
    209 Green Bay Oncology - Iron Mountain Iron Mountain Michigan United States 49801
    210 Allegiance Health Jackson Michigan United States 49201
    211 Bronson Methodist Hospital Kalamazoo Michigan United States 49007
    212 West Michigan Cancer Center Kalamazoo Michigan United States 49007
    213 Borgess Medical Center Kalamazoo Michigan United States 49048
    214 Sparrow Hospital Lansing Michigan United States 48912
    215 Trinity Health Saint Mary Mercy Livonia Hospital Livonia Michigan United States 48154
    216 UP Health System Marquette Marquette Michigan United States 49855
    217 Mercy Memorial Hospital Monroe Michigan United States 48162
    218 Toledo Clinic Cancer Centers-Monroe Monroe Michigan United States 48162
    219 Lakeland Hospital Niles Niles Michigan United States 49120
    220 Saint Joseph Mercy Oakland Pontiac Michigan United States 48341
    221 Lake Huron Medical Center Port Huron Michigan United States 48060
    222 Ascension Saint Mary's Hospital Saginaw Michigan United States 48601
    223 Lakeland Medical Center Saint Joseph Saint Joseph Michigan United States 49085
    224 Marie Yeager Cancer Center Saint Joseph Michigan United States 49085
    225 Ascension Providence Hospitals - Southfield Southfield Michigan United States 48075
    226 William Beaumont Hospital - Troy Troy Michigan United States 48085
    227 Saint John Macomb-Oakland Hospital Warren Michigan United States 48093
    228 Medini, Eitan MD (UIA Investigator) Alexandria Minnesota United States 56308
    229 Fairview Ridges Hospital Burnsville Minnesota United States 55337
    230 Mercy Hospital Coon Rapids Minnesota United States 55433
    231 Essentia Health Cancer Center Duluth Minnesota United States 55805
    232 Fairview Southdale Hospital Edina Minnesota United States 55435
    233 Lake Region Healthcare Corporation-Cancer Care Fergus Falls Minnesota United States 56537
    234 Unity Hospital Fridley Minnesota United States 55432
    235 Hutchinson Area Health Care Hutchinson Minnesota United States 55350
    236 Minnesota Oncology Hematology PA-Maplewood Maplewood Minnesota United States 55109
    237 Saint John's Hospital - Healtheast Maplewood Minnesota United States 55109
    238 Abbott-Northwestern Hospital Minneapolis Minnesota United States 55407
    239 Hennepin County Medical Center Minneapolis Minnesota United States 55415
    240 Minneapolis VA Medical Center Minneapolis Minnesota United States 55417
    241 Health Partners Inc Minneapolis Minnesota United States 55454
    242 North Memorial Medical Health Center Robbinsdale Minnesota United States 55422
    243 Mayo Clinic in Rochester Rochester Minnesota United States 55905
    244 Coborn Cancer Center at Saint Cloud Hospital Saint Cloud Minnesota United States 56303
    245 Saint Cloud Hospital Saint Cloud Minnesota United States 56303
    246 Metro Minnesota Community Oncology Research Consortium Saint Louis Park Minnesota United States 55416
    247 Park Nicollet Clinic - Saint Louis Park Saint Louis Park Minnesota United States 55416
    248 Regions Hospital Saint Paul Minnesota United States 55101
    249 United Hospital Saint Paul Minnesota United States 55102
    250 Saint Francis Regional Medical Center Shakopee Minnesota United States 55379
    251 Lakeview Hospital Stillwater Minnesota United States 55082
    252 Ridgeview Medical Center Waconia Minnesota United States 55387
    253 Rice Memorial Hospital Willmar Minnesota United States 56201
    254 Minnesota Oncology Hematology PA-Woodbury Woodbury Minnesota United States 55125
    255 Keesler Medical Center Keesler Air Force Base Mississippi United States 39534
    256 Singing River Hospital Pascagoula Mississippi United States 39581
    257 Saint Francis Medical Center Cape Girardeau Missouri United States 63703
    258 Southeast Cancer Center Cape Girardeau Missouri United States 63703
    259 University of Missouri - Ellis Fischel Columbia Missouri United States 65212
    260 Capital Region Southwest Campus Jefferson City Missouri United States 65109
    261 Truman Medical Centers Kansas City Missouri United States 64108
    262 Saint Luke's Hospital of Kansas City Kansas City Missouri United States 64111
    263 Saint Joseph Health Center Kansas City Missouri United States 64114
    264 North Kansas City Hospital Kansas City Missouri United States 64116
    265 Heartland Hematology and Oncology Associates Incorporated Kansas City Missouri United States 64118
    266 Kansas City Veterans Affairs Medical Center Kansas City Missouri United States 64128
    267 Research Medical Center Kansas City Missouri United States 64132
    268 Saint Luke's East - Lee's Summit Lee's Summit Missouri United States 64086
    269 Liberty Radiation Oncology Center Liberty Missouri United States 64068
    270 Heartland Regional Medical Center Saint Joseph Missouri United States 64506
    271 Saint Joseph Oncology Inc Saint Joseph Missouri United States 64507
    272 Mercy Hospital South Saint Louis Missouri United States 63128
    273 Missouri Baptist Medical Center Saint Louis Missouri United States 63131
    274 Center for Cancer Care and Research Saint Louis Missouri United States 63141
    275 Comprehensive Cancer Care PC Saint Louis Missouri United States 63141
    276 Mercy Hospital Springfield Springfield Missouri United States 65804
    277 Billings Clinic Cancer Center Billings Montana United States 59101
    278 Northern Rockies Radiation Oncology Center Billings Montana United States 59101
    279 Saint Vincent Healthcare Billings Montana United States 59101
    280 Montana Cancer Consortium NCORP Billings Montana United States 59102
    281 Saint Vincent Frontier Cancer Center Billings Montana United States 59102
    282 Bozeman Deaconess Hospital Bozeman Montana United States 59715
    283 Saint James Community Hospital and Cancer Treatment Center Butte Montana United States 59701
    284 Benefis Healthcare- Sletten Cancer Institute Great Falls Montana United States 59405
    285 Berdeaux, Donald MD (UIA Investigator) Great Falls Montana United States 59405
    286 Great Falls Clinic Great Falls Montana United States 59405
    287 Northern Montana Hospital Havre Montana United States 59501
    288 Saint Peter's Community Hospital Helena Montana United States 59601
    289 Glacier Oncology PLLC Kalispell Montana United States 59901
    290 Kalispell Medical Oncology Kalispell Montana United States 59901
    291 Kalispell Regional Medical Center Kalispell Montana United States 59901
    292 Montana Cancer Specialists Missoula Montana United States 59802
    293 Saint Patrick Hospital - Community Hospital Missoula Montana United States 59802
    294 Community Medical Hospital Missoula Montana United States 59804
    295 Guardian Oncology and Center for Wellness Missoula Montana United States 59804
    296 CHI Health Saint Francis Grand Island Nebraska United States 68803
    297 CHI Health Good Samaritan Kearney Nebraska United States 68847
    298 Nebraska Cancer Research Center Lincoln Nebraska United States 68510
    299 Missouri Valley Cancer Consortium Omaha Nebraska United States 68106
    300 Alegent Health Immanuel Medical Center Omaha Nebraska United States 68122
    301 Alegent Health Bergan Mercy Medical Center Omaha Nebraska United States 68124
    302 Creighton University Medical Center Omaha Nebraska United States 68131
    303 University of Nebraska Medical Center Omaha Nebraska United States 68198
    304 University Medical Center of Southern Nevada Las Vegas Nevada United States 89102
    305 Summerlin Hospital Medical Center Las Vegas Nevada United States 89144
    306 OptumCare Cancer Care at Fort Apache Las Vegas Nevada United States 89148
    307 Nevada Cancer Research Foundation NCORP Las Vegas Nevada United States 89169
    308 Cheshire Medical Center-Dartmouth-Hitchcock Keene Keene New Hampshire United States 03431
    309 Cooper Hospital University Medical Center Camden New Jersey United States 08103
    310 Veterans Adminstration New Jersey Health Care System East Orange New Jersey United States 07018-1095
    311 Virtua Memorial Mount Holly New Jersey United States 08060
    312 Inspira Medical Center Mullica Hill Mullica Hill New Jersey United States 08062
    313 Jersey Shore Medical Center Neptune New Jersey United States 07753
    314 Newark Beth Israel Medical Center Newark New Jersey United States 07112
    315 Riverview Medical Center/Booker Cancer Center Red Bank New Jersey United States 07701
    316 Community Medical Center Toms River New Jersey United States 08755
    317 Inspira Medical Center Vineland Vineland New Jersey United States 08360
    318 Virtua Voorhees Voorhees New Jersey United States 08043
    319 Montefiore Medical Center-Weiler Hospital Bronx New York United States 10461
    320 Montefiore Medical Center - Moses Campus Bronx New York United States 10467
    321 Hematology Oncology Associates of Central New York-East Syracuse East Syracuse New York United States 13057
    322 Glens Falls Hospital Glens Falls New York United States 12801
    323 Garnet Health Medical Center Middletown New York United States 10940
    324 NYU Winthrop Hospital Mineola New York United States 11501
    325 Laura and Isaac Perlmutter Cancer Center at NYU Langone New York New York United States 10016
    326 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    327 Highland Hospital Rochester New York United States 14620
    328 University of Rochester Rochester New York United States 14642
    329 State University of New York Upstate Medical University Syracuse New York United States 13210
    330 Mission Hospital Asheville North Carolina United States 28801
    331 Southeastern Medical Oncology Center-Clinton Clinton North Carolina United States 28328
    332 Southeastern Medical Oncology Center-Goldsboro Goldsboro North Carolina United States 27534
    333 Wayne Memorial Hospital Goldsboro North Carolina United States 27534
    334 Southeastern Medical Oncology Center-Jacksonville Jacksonville North Carolina United States 28546
    335 UNC Rex Cancer Center Raleigh North Carolina United States 27607
    336 Rex Cancer Center of Wakefield Raleigh North Carolina United States 27614
    337 Iredell Memorial Hospital Statesville North Carolina United States 28677
    338 Wake Forest University Health Sciences Winston-Salem North Carolina United States 27157
    339 Mid Dakota Clinic Bismarck North Dakota United States 58501
    340 Saint Alexius Medical Center Bismarck North Dakota United States 58501
    341 Sanford Bismarck Medical Center Bismarck North Dakota United States 58501
    342 Toledo Clinic Cancer Centers-Bowling Green Bowling Green Ohio United States 43402
    343 Cleveland Clinic Mercy Hospital Canton Ohio United States 44708
    344 Aultman Health Foundation Canton Ohio United States 44710
    345 Good Samaritan Hospital - Cincinnati Cincinnati Ohio United States 45220
    346 TriHealth Cancer Institute-Westside Cincinnati Ohio United States 45247
    347 TriHealth Cancer Institute-Anderson Cincinnati Ohio United States 45255
    348 Case Western Reserve University Cleveland Ohio United States 44106
    349 MetroHealth Medical Center Cleveland Ohio United States 44109
    350 North Coast Cancer Care-Clyde Clyde Ohio United States 43410
    351 Grandview Hospital Dayton Ohio United States 45405
    352 Good Samaritan Hospital - Dayton Dayton Ohio United States 45406
    353 Miami Valley Hospital Dayton Ohio United States 45409
    354 Miami Valley Hospital North Dayton Ohio United States 45415
    355 Dayton NCI Community Oncology Research Program Dayton Ohio United States 45459
    356 Hematology Oncology Center Incorporated Elyria Ohio United States 44035
    357 Mercy Cancer Center-Elyria Elyria Ohio United States 44035
    358 Blanchard Valley Hospital Findlay Ohio United States 45840
    359 Atrium Medical Center-Middletown Regional Hospital Franklin Ohio United States 45005-1066
    360 Wayne Hospital Greenville Ohio United States 45331
    361 Kettering Medical Center Kettering Ohio United States 45429
    362 Saint Rita's Medical Center Lima Ohio United States 45801
    363 Lima Memorial Hospital Lima Ohio United States 45804
    364 Saint Luke's Hospital Maumee Ohio United States 43537
    365 Toledo Clinic Cancer Centers-Maumee Maumee Ohio United States 43537
    366 Toledo Radiation Oncology at Northwest Ohio Onocolgy Center Maumee Ohio United States 43537
    367 Fisher-Titus Medical Center Norwalk Ohio United States 44857
    368 Saint Charles Hospital Oregon Ohio United States 43616
    369 Toledo Clinic Cancer Centers-Oregon Oregon Ohio United States 43616
    370 North Coast Cancer Care Sandusky Ohio United States 44870
    371 ProMedica Flower Hospital Sylvania Ohio United States 43560
    372 Mercy Hospital of Tiffin Tiffin Ohio United States 44883
    373 ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital Toledo Ohio United States 43606
    374 Saint Vincent Mercy Medical Center Toledo Ohio United States 43608
    375 University of Toledo Toledo Ohio United States 43614
    376 Toledo Community Hospital Oncology Program CCOP Toledo Ohio United States 43617
    377 Mercy Health - Saint Anne Hospital Toledo Ohio United States 43623
    378 Toledo Clinic Cancer Centers-Toledo Toledo Ohio United States 43623
    379 Upper Valley Medical Center Troy Ohio United States 45373
    380 Fulton County Health Center Wauseon Ohio United States 43567
    381 Clinton Memorial Hospital Wilmington Ohio United States 45177
    382 Greene Memorial Hospital Xenia Ohio United States 45385
    383 University of Oklahoma Health Sciences Center Oklahoma City Oklahoma United States 73104
    384 Clackamas Radiation Oncology Center Clackamas Oregon United States 97015
    385 Bay Area Hospital Coos Bay Oregon United States 97420
    386 Providence Newberg Medical Center Newberg Oregon United States 97132
    387 Providence Willamette Falls Medical Center Oregon City Oregon United States 97045
    388 Providence Portland Medical Center Portland Oregon United States 97213
    389 Providence Saint Vincent Medical Center Portland Oregon United States 97225
    390 Jefferson Abington Hospital Abington Pennsylvania United States 19001
    391 Bryn Mawr Hospital Bryn Mawr Pennsylvania United States 19010
    392 Butler Memorial Hospital Butler Pennsylvania United States 16001
    393 Carlisle Regional Cancer Center Carlisle Pennsylvania United States 17015
    394 Geisinger Medical Center Danville Pennsylvania United States 17822
    395 Ephrata Cancer Center Ephrata Pennsylvania United States 17522
    396 Ephrata Community Hospital Ephrata Pennsylvania United States 17522
    397 Adams Cancer Center Gettysburg Pennsylvania United States 17325
    398 Cherry Tree Cancer Center Hanover Pennsylvania United States 17331
    399 Geisinger Medical Center-Cancer Center Hazleton Hazleton Pennsylvania United States 18201
    400 Penn State Milton S Hershey Medical Center Hershey Pennsylvania United States 17033-0850
    401 Lewistown Hospital Lewistown Pennsylvania United States 17044
    402 Riddle Memorial Hospital Media Pennsylvania United States 19063
    403 Paoli Memorial Hospital Paoli Pennsylvania United States 19301
    404 University of Pennsylvania/Abramson Cancer Center Philadelphia Pennsylvania United States 19104
    405 Pennsylvania Hospital Philadelphia Pennsylvania United States 19107
    406 Phoenixville Hospital Phoenixville Pennsylvania United States 19460
    407 Pottstown Hospital Pottstown Pennsylvania United States 19464
    408 Penn State Health Saint Joseph Medical Center Reading Pennsylvania United States 19605
    409 Guthrie Medical Group PC-Robert Packer Hospital Sayre Pennsylvania United States 18840
    410 Geisinger Medical Group State College Pennsylvania United States 16801
    411 Mount Nittany Medical Center State College Pennsylvania United States 16803
    412 Chester County Hospital West Chester Pennsylvania United States 19380
    413 Reading Hospital West Reading Pennsylvania United States 19611
    414 Geisinger Wyoming Valley/Henry Cancer Center Wilkes-Barre Pennsylvania United States 18711
    415 UPMC Susquehanna Williamsport Pennsylvania United States 17701
    416 Lankenau Medical Center Wynnewood Pennsylvania United States 19096
    417 WellSpan Health-York Hospital York Pennsylvania United States 17403
    418 Prisma Health Cancer Institute - Spartanburg Boiling Springs South Carolina United States 29316
    419 Prisma Health Cancer Institute - Easley Easley South Carolina United States 29640
    420 Greenville Health System Cancer Institute-Andrews Greenville South Carolina United States 29601
    421 Saint Francis Hospital Greenville South Carolina United States 29601
    422 Prisma Health Cancer Institute - Butternut Greenville South Carolina United States 29605
    423 Prisma Health Cancer Institute - Faris Greenville South Carolina United States 29605
    424 Prisma Health Greenville Memorial Hospital Greenville South Carolina United States 29605
    425 Prisma Health Cancer Institute - Eastside Greenville South Carolina United States 29615
    426 Self Regional Healthcare Greenwood South Carolina United States 29646
    427 Prisma Health Cancer Institute - Greer Greer South Carolina United States 29650
    428 Prisma Health Cancer Institute - Seneca Seneca South Carolina United States 29672
    429 Rapid City Regional Hospital Rapid City South Dakota United States 57701
    430 Avera Cancer Institute Sioux Falls South Dakota United States 57105
    431 Avera McKennan Hospital and University Health Center Sioux Falls South Dakota United States 57117-5045
    432 Thompson Cancer Survival Center Knoxville Tennessee United States 37916
    433 The Don and Sybil Harrington Cancer Center Amarillo Texas United States 79106
    434 University of Virginia Cancer Center Charlottesville Virginia United States 22908
    435 Danville Regional Medical Center Danville Virginia United States 24541
    436 Fredericksburg Oncology Inc Fredericksburg Virginia United States 22401
    437 Sovah Health Martinsville Martinsville Virginia United States 24115
    438 PeaceHealth Saint Joseph Medical Center Bellingham Washington United States 98225
    439 Harrison HealthPartners Hematology and Oncology-Bremerton Bremerton Washington United States 98310
    440 Swedish Cancer Institute-Edmonds Edmonds Washington United States 98026
    441 Kadlec Clinic Hematology and Oncology Kennewick Washington United States 99336
    442 EvergreenHealth Medical Center Kirkland Washington United States 98033
    443 PeaceHealth Saint John Medical Center Longview Washington United States 98632
    444 Skagit Valley Hospital Mount Vernon Washington United States 98274
    445 Harrison HealthPartners Hematology and Oncology-Poulsbo Poulsbo Washington United States 98370
    446 Virginia Mason Medical Center Seattle Washington United States 98101
    447 Minor and James Medical PLLC Seattle Washington United States 98104
    448 Pacific Medical Center-First Hill Seattle Washington United States 98104
    449 Swedish Medical Center-Ballard Campus Seattle Washington United States 98107
    450 Kaiser Permanente Washington Seattle Washington United States 98112
    451 Swedish Medical Center-First Hill Seattle Washington United States 98122-4307
    452 University of Washington Medical Center - Montlake Seattle Washington United States 98195
    453 Cancer Care Northwest - Spokane South Spokane Washington United States 99202
    454 Evergreen Hematology and Oncology PS Spokane Washington United States 99218
    455 PeaceHealth Southwest Medical Center Vancouver Washington United States 98664
    456 Wenatchee Valley Hospital and Clinics Wenatchee Washington United States 98801
    457 West Virginia University Charleston Division Charleston West Virginia United States 25304
    458 West Virginia University Healthcare Morgantown West Virginia United States 26506
    459 Camden Clark Medical Center Parkersburg West Virginia United States 26101
    460 Princeton Community Hospital Princeton West Virginia United States 24740
    461 ThedaCare Regional Cancer Center Appleton Wisconsin United States 54911
    462 Aurora Cancer Care-Southern Lakes VLCC Burlington Wisconsin United States 53105
    463 Marshfield Clinic-Chippewa Center Chippewa Falls Wisconsin United States 54729
    464 Marshfield Clinic Cancer Center at Sacred Heart Eau Claire Wisconsin United States 54701
    465 Aurora Health Care Germantown Health Center Germantown Wisconsin United States 53022
    466 Aurora Cancer Care-Grafton Grafton Wisconsin United States 53024
    467 Green Bay Oncology at Saint Vincent Hospital Green Bay Wisconsin United States 54301-3526
    468 Saint Vincent Hospital Cancer Center Green Bay Green Bay Wisconsin United States 54301
    469 Green Bay Oncology Limited at Saint Mary's Hospital Green Bay Wisconsin United States 54303
    470 Saint Vincent Hospital Cancer Center at Saint Mary's Green Bay Wisconsin United States 54303
    471 Aurora BayCare Medical Center Green Bay Wisconsin United States 54311
    472 Mercyhealth Hospital and Cancer Center - Janesville Janesville Wisconsin United States 53548
    473 UW Cancer Center Johnson Creek Johnson Creek Wisconsin United States 53038
    474 Aurora Cancer Care-Kenosha South Kenosha Wisconsin United States 53142
    475 Gundersen Lutheran Medical Center La Crosse Wisconsin United States 54601
    476 Dean Hematology and Oncology Clinic Madison Wisconsin United States 53717
    477 University of Wisconsin Carbone Cancer Center Madison Wisconsin United States 53792
    478 Holy Family Memorial Hospital Manitowoc Wisconsin United States 54221
    479 Aurora Bay Area Medical Group-Marinette Marinette Wisconsin United States 54143
    480 Bay Area Medical Center Marinette Wisconsin United States 54143
    481 Marshfield Medical Center-Marshfield Marshfield Wisconsin United States 54449
    482 Marshfield Medical Center Marshfield Wisconsin United States 54449
    483 Aurora Cancer Care-Milwaukee Milwaukee Wisconsin United States 53209
    484 Aurora Saint Luke's Medical Center Milwaukee Wisconsin United States 53215
    485 Medical College of Wisconsin Milwaukee Wisconsin United States 53226
    486 Aurora Sinai Medical Center Milwaukee Wisconsin United States 53233
    487 Marshfield Clinic-Minocqua Center Minocqua Wisconsin United States 54548
    488 ProHealth D N Greenwald Center Mukwonago Wisconsin United States 53149
    489 Cancer Center of Western Wisconsin New Richmond Wisconsin United States 54017
    490 ProHealth Oconomowoc Memorial Hospital Oconomowoc Wisconsin United States 53066
    491 Saint Vincent Hospital Cancer Center at Oconto Falls Oconto Falls Wisconsin United States 54154
    492 Vince Lombardi Cancer Clinic - Oshkosh Oshkosh Wisconsin United States 54904
    493 Aurora Cancer Care-Racine Racine Wisconsin United States 53406
    494 Ascension Saint Mary's Hospital Rhinelander Wisconsin United States 54501
    495 Marshfield Medical Center-Rice Lake Rice Lake Wisconsin United States 54868
    496 HSHS Saint Nicholas Hospital Sheboygan Wisconsin United States 53081
    497 Vince Lombardi Cancer Clinic-Sheboygan Sheboygan Wisconsin United States 53081
    498 Ascension Saint Michael's Hospital Stevens Point Wisconsin United States 54481
    499 Saint Vincent Hospital Cancer Center at Sturgeon Bay Sturgeon Bay Wisconsin United States 54235-1495
    500 Green Bay Oncology - Sturgeon Bay Sturgeon Bay Wisconsin United States 54235
    501 Aurora Medical Center in Summit Summit Wisconsin United States 53066
    502 Vince Lombardi Cancer Clinic-Two Rivers Two Rivers Wisconsin United States 54241
    503 Aurora Cancer Care-Waukesha Waukesha Wisconsin United States 53188
    504 ProHealth Waukesha Memorial Hospital Waukesha Wisconsin United States 53188
    505 UW Cancer Center at ProHealth Care Waukesha Wisconsin United States 53188
    506 Aspirus Regional Cancer Center Wausau Wisconsin United States 54401
    507 Aurora Cancer Care-Milwaukee West Wauwatosa Wisconsin United States 53226
    508 Aurora West Allis Medical Center West Allis Wisconsin United States 53227
    509 Marshfield Medical Center - Weston Weston Wisconsin United States 54476
    510 Aspirus Cancer Care - Wisconsin Rapids Wisconsin Rapids Wisconsin United States 54494
    511 Marshfield Clinic - Wisconsin Rapids Center Wisconsin Rapids Wisconsin United States 54494
    512 Rocky Mountain Oncology Casper Wyoming United States 82609
    513 Welch Cancer Center Sheridan Wyoming United States 82801

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Alan F List, ECOG-ACRIN Cancer Research Group

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00843882
    Other Study ID Numbers:
    • NCI-2009-01173
    • NCI-2009-01173
    • CDR0000634119
    • ECOG-E2905
    • 09-0095
    • E2905
    • E2905
    • E2905
    • U10CA180820
    • U10CA021115
    • U24CA196172
    First Posted:
    Feb 13, 2009
    Last Update Posted:
    Jul 28, 2022
    Last Verified:
    Jul 1, 2022
    Additional relevant MeSH terms:
    Preleukemia
    Leukemia, Myelomonocytic, Chronic
    Leukemia, Myelomonocytic, Juvenile
    Anemia
    Myelodysplastic Syndromes
    Syndrome
    Lenalidomide
    Epoetin Alfa

    Study Results

    Participant Flow

    Recruitment Details From January 2009 through May 2016, the trial enrolled a total of 247 patients.
    Pre-assignment Detail
    Arm/Group Title Arm A (Lenalidomide; Chromosome 5q31.1 Deletion) Arm A (Lenalidomide; Randomization) Arm B (Lenalidomide + Epoetin Alfa; Randomization)
    Arm/Group Description Patients receive lenalidomide PO QD on days 1-21. Patients receive lenalidomide PO QD on days 1-21. Patients receive lenalidomide PO QD on days 1-21 and epoetin alfa SC once weekly.
    Period Title: Step 1
    STARTED 38 103 106
    Treated Patients 36 103 106
    Evaluable Patients Included in Primary Analysis 0 96 99
    Patients With Cytogenetic Response Data Available 0 55 51
    COMPLETED 6 48 41
    NOT COMPLETED 32 55 65
    Period Title: Step 1
    STARTED 7 46 0
    Evaluable Patients Included in Primary Analysis 7 37 0
    COMPLETED 3 20 0
    NOT COMPLETED 4 26 0

    Baseline Characteristics

    Arm/Group Title Arm A (Lenalidomide; Chromosome 5q31.1 Deletion) Arm A (Lenalidomide; Randomization) Arm B (Lenalidomide + Epoetin Alfa; Randomization) Total
    Arm/Group Description Patients receive lenalidomide PO QD on days 1-21. Patients receive lenalidomide PO QD on days 1-21. Patients receive lenalidomide PO QD on days 1-21 and epoetin alfa SC once weekly. Total of all reporting groups
    Overall Participants 38 103 106 247
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    77
    74
    73
    74
    Sex: Female, Male (Count of Participants)
    Female
    26
    68.4%
    33
    32%
    28
    26.4%
    87
    35.2%
    Male
    12
    31.6%
    70
    68%
    78
    73.6%
    160
    64.8%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    2
    5.3%
    2
    1.9%
    1
    0.9%
    5
    2%
    Not Hispanic or Latino
    34
    89.5%
    96
    93.2%
    97
    91.5%
    227
    91.9%
    Unknown or Not Reported
    2
    5.3%
    5
    4.9%
    8
    7.5%
    15
    6.1%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    1
    2.6%
    1
    1%
    3
    2.8%
    5
    2%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    1
    1%
    3
    2.8%
    4
    1.6%
    White
    35
    92.1%
    97
    94.2%
    96
    90.6%
    228
    92.3%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    2
    5.3%
    4
    3.9%
    4
    3.8%
    10
    4%

    Outcome Measures

    1. Primary Outcome
    Title Proportion of Patients With Major Erythroid Response (MER)
    Description 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.
    Time Frame Assessed after completion of 16 weeks of treatment

    Outcome Measure Data

    Analysis Population Description
    Evaluable patients randomized to either arm A or arm B
    Arm/Group Title Arm A (Lenalidomide; Randomization) Arm B (Lenalidomide + Epoetin Alfa; Randomization)
    Arm/Group Description Patients receive lenalidomide PO QD on days 1-21. Patients receive lenalidomide PO QD on days 1-21 and epoetin alfa SC once weekly.
    Measure Participants 96 99
    Number (90% Confidence Interval) [proportion of participants]
    0.115
    0.3%
    0.283
    0.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A (Lenalidomide; Randomization), Arm B (Lenalidomide + Epoetin Alfa; Randomization)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.004
    Comments
    Method Fisher Exact
    Comments
    2. Secondary Outcome
    Title Time to Major Erythroid Response (MER)
    Description 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.
    Time Frame Assessed every cycle during treatment and then 3 and 6 months after last protocol treatment

    Outcome Measure Data

    Analysis Population Description
    Only evaluable patients who achieved MER among randomized patients were included in this analysis.
    Arm/Group Title Arm A (Lenalidomide; Randomization) Arm B (Lenalidomide + Epoetin Alfa; Randomization)
    Arm/Group Description Patients receive lenalidomide PO QD on days 1-21. Patients receive lenalidomide PO QD on days 1-21 and epoetin alfa SC once weekly.
    Measure Participants 11 28
    Median (Full Range) [months]
    3.6
    3.7
    3. Secondary Outcome
    Title Duration of Major Erythroid Response (MER)
    Description 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.
    Time Frame Assessed every cycle during treatment and then 3 and 6 months after last protocol treatment

    Outcome Measure Data

    Analysis Population Description
    Only evaluable patients who achieved MER among randomized patients were included in this analysis.
    Arm/Group Title Arm A (Lenalidomide; Randomization) Arm B (Lenalidomide + Epoetin Alfa; Randomization)
    Arm/Group Description Patients receive lenalidomide PO QD on days 1-21. Patients receive lenalidomide PO QD on days 1-21 and epoetin alfa SC once weekly.
    Measure Participants 11 28
    Median (95% Confidence Interval) [months]
    13
    23.8
    4. Secondary Outcome
    Title Proportion of Patients With Major Erythroid Response (MER) to Salvage Combination Therapy
    Description 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.
    Time Frame Assessed after completion of 16 weeks of treatment

    Outcome Measure Data

    Analysis Population Description
    Evaluable patients who fail to experience a MER with lenalidomide monotherapy and receive salvage combination therapy (crossover from arm A to arm B)
    Arm/Group Title Arm B (Lenalidomide + Epoetin Alfa; Crossover)
    Arm/Group Description Patients receive lenalidomide PO QD on days 1-21 and epoetin alfa SC once weekly.
    Measure Participants 44
    Number (95% Confidence Interval) [proportion of participants]
    0.25
    0.7%
    5. Secondary Outcome
    Title Proportion of Patients With Minor Erythroid Response
    Description 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.
    Time Frame Assessed every cycle during treatment and after completion of 16 weeks of treatment

    Outcome Measure Data

    Analysis Population Description
    Evaluable patients randomized to either arm A or arm B
    Arm/Group Title Arm A (Lenalidomide; Randomization) Arm B (Lenalidomide + Epoetin Alfa; Randomization)
    Arm/Group Description Patients receive lenalidomide PO QD on days 1-21. Patients receive lenalidomide PO QD on days 1-21 and epoetin alfa SC once weekly.
    Measure Participants 96 99
    Number (90% Confidence Interval) [proportion of participants]
    0.208
    0.5%
    0.182
    0.2%
    6. Secondary Outcome
    Title Proportion of Patients With Major Erythroid Response (MER) Among Those With Chromosome 5q31.1 Deletion
    Description 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.
    Time Frame Assessed after completion of 16 weeks of treatment

    Outcome Measure Data

    Analysis Population Description
    All patients with chromosome 5q31.1 deletion in arm A
    Arm/Group Title Arm A (Lenalidomide; Chromosome 5q31.1 Deletion)
    Arm/Group Description Patients receive lenalidomide PO QD on days 1-21.
    Measure Participants 38
    Number (95% Confidence Interval) [proportion of participants]
    0.632
    1.7%
    7. Secondary Outcome
    Title Proportion of Patients With Bone Marrow Response
    Description 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.
    Time Frame Assessed at 16 weeks

    Outcome Measure Data

    Analysis Population Description
    Evaluable patients randomized to either arm A or arm B
    Arm/Group Title Arm A (Lenalidomide; Randomization) Arm B (Lenalidomide + Epoetin Alfa; Randomization)
    Arm/Group Description Patients receive lenalidomide PO QD on days 1-21. Patients receive lenalidomide PO QD on days 1-21 and epoetin alfa SC once weekly.
    Measure Participants 96 99
    Number (90% Confidence Interval) [proportion of participants]
    0.01
    0%
    0.03
    0%
    8. Secondary Outcome
    Title Proportion of Patients With Cytogenetic Response
    Description 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.
    Time Frame Assessed at baseline and after completion of 16 weeks of treatment

    Outcome Measure Data

    Analysis Population Description
    Evaluable patients randomized to either arm A or arm B who had cytogenetic response data
    Arm/Group Title Arm A (Lenalidomide; Randomization) Arm B (Lenalidomide + Epoetin Alfa; Randomization)
    Arm/Group Description Patients receive lenalidomide PO QD on days 1-21. Patients receive lenalidomide PO QD on days 1-21 and epoetin alfa SC once weekly.
    Measure Participants 55 51
    Number (95% Confidence Interval) [proportion of participants]
    0.07
    0.2%
    0.10
    0.1%
    9. Secondary Outcome
    Title Association Between Major Erythroid Response and Cytogenetic Response
    Description 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.
    Time Frame Assessed at baseline and after completion of 16 weeks of treatment

    Outcome Measure Data

    Analysis Population Description
    Evaluable patients in both arms A and B who had both major erythroid response data and cytogenetic response data
    Arm/Group Title Major Erythroid Response No Major Erythroid Response
    Arm/Group Description Patients with major erythroid response Patients without major erythroid response
    Measure Participants 23 83
    Cytogenetic response
    4
    10.5%
    5
    4.9%
    No cytogenetic response
    19
    50%
    78
    75.7%
    10. Secondary Outcome
    Title Pretreatment Endogenous Erythropoietin Level
    Description 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.
    Time Frame Assessed at baseline and after completion of 16 weeks of treatment

    Outcome Measure Data

    Analysis Population Description
    All patients randomized to arm A and all patients with 5q31.1 deletion that received lenalidomide alone
    Arm/Group Title Arm A Patients With Major Erythroid Response Arm A Patients Without Major Erythroid Response
    Arm/Group Description Patients receive lenalidomide PO QD on days 1-21 and achieve major erythroid response. Patients receive lenalidomide PO QD on days 1-21 and achieve major erythroid response.
    Measure Participants 36 105
    Median (Full Range) [mU/mL]
    514.5
    150
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A (Lenalidomide; Randomization), Arm B (Lenalidomide + Epoetin Alfa; Randomization)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0002
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    11. Other Pre-specified Outcome
    Title The Association Between CD45 Isoform Profile and ex Vivo Augmentation of STAT5 Phosphorylation by Lenalidomide
    Description 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.
    Time Frame Assessed at baseline and after completion of 16 weeks of treatment

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    12. Other Pre-specified Outcome
    Title RNA and Protein Expression Level of Cdc25C, PP2A and Their Phosphatase Substrates, Cdc2phospho-Tyr15 and Cdc25Cphospho-Ser216
    Description To characterize molecular targets relevant to lenalidomide cytotoxicity in del5q31.1 cells.
    Time Frame Assessed at baseline and after completion of 16 weeks of treatment

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    13. Other Pre-specified Outcome
    Title Proportion of Patients With Cryptic Chromosome 5q31.1 Deletions
    Description 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.
    Time Frame Assessed at baseline and after completion of 16 weeks of treatment

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description

    Adverse Events

    Time Frame Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
    Adverse Event Reporting Description Adverse events were assessed among patients who started protocol treatment. All-cause mortality was assessed among all registered patients.
    Arm/Group Title Arm A (Step 1; Regardless of Chromosome 5q31.1 Status) Arm B (Step 1 Randomization; Lenalidomide + Epoetin Alfa) Arm B (Step 2 Cross-over; Lenalidomide + Epoetin Alfa)
    Arm/Group Description Patients receive lenalidomide PO QD on days 1-21. Patients receive lenalidomide PO QD on days 1-21 and epoetin alfa SC once weekly. Patients receive lenalidomide PO QD on days 1-21 and epoetin alfa SC once weekly.
    All Cause Mortality
    Arm A (Step 1; Regardless of Chromosome 5q31.1 Status) Arm B (Step 1 Randomization; Lenalidomide + Epoetin Alfa) Arm B (Step 2 Cross-over; Lenalidomide + Epoetin Alfa)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 29/141 (20.6%) 29/106 (27.4%) 0/53 (0%)
    Serious Adverse Events
    Arm A (Step 1; Regardless of Chromosome 5q31.1 Status) Arm B (Step 1 Randomization; Lenalidomide + Epoetin Alfa) Arm B (Step 2 Cross-over; Lenalidomide + Epoetin Alfa)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 123/139 (88.5%) 98/106 (92.5%) 49/53 (92.5%)
    Blood and lymphatic system disorders
    Anemia 80/139 (57.6%) 65/106 (61.3%) 30/53 (56.6%)
    Febrile neutropenia 6/139 (4.3%) 4/106 (3.8%) 0/53 (0%)
    Cardiac disorders
    Acute coronary syndrome 0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Atrial fibrillation 2/139 (1.4%) 1/106 (0.9%) 0/53 (0%)
    Chest pain - cardiac 0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Heart failure 1/139 (0.7%) 1/106 (0.9%) 0/53 (0%)
    Left ventricular systolic dysfunction 0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Myocardial infarction 0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Cardiac disorders - Other, specify 0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Eye disorders
    Optic nerve disorder 0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Gastrointestinal disorders
    Abdominal pain 1/139 (0.7%) 1/106 (0.9%) 0/53 (0%)
    Colitis 1/139 (0.7%) 1/106 (0.9%) 0/53 (0%)
    Colonic obstruction 1/139 (0.7%) 0/106 (0%) 0/53 (0%)
    Constipation 0/139 (0%) 1/106 (0.9%) 1/53 (1.9%)
    Diarrhea 4/139 (2.9%) 3/106 (2.8%) 1/53 (1.9%)
    Nausea 0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Vomiting 1/139 (0.7%) 1/106 (0.9%) 0/53 (0%)
    General disorders
    Edema limbs 1/139 (0.7%) 1/106 (0.9%) 1/53 (1.9%)
    Fatigue 4/139 (2.9%) 8/106 (7.5%) 2/53 (3.8%)
    Fever 0/139 (0%) 2/106 (1.9%) 0/53 (0%)
    Multi-organ failure 0/139 (0%) 0/106 (0%) 1/53 (1.9%)
    Non-cardiac chest pain 1/139 (0.7%) 0/106 (0%) 0/53 (0%)
    Immune system disorders
    Anaphylaxis 0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Immune system disorders - Other, specify 0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Infections and infestations
    Bronchial infection 1/139 (0.7%) 0/106 (0%) 0/53 (0%)
    Lung infection 2/139 (1.4%) 2/106 (1.9%) 0/53 (0%)
    Sepsis 1/139 (0.7%) 2/106 (1.9%) 0/53 (0%)
    Soft tissue infection 1/139 (0.7%) 1/106 (0.9%) 0/53 (0%)
    Urinary tract infection 0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Wound infection 0/139 (0%) 0/106 (0%) 1/53 (1.9%)
    Infections and infestations - Other 0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Investigations
    Blood bilirubin increased 1/139 (0.7%) 1/106 (0.9%) 0/53 (0%)
    Creatinine increased 3/139 (2.2%) 5/106 (4.7%) 1/53 (1.9%)
    Hemoglobin increased 1/139 (0.7%) 0/106 (0%) 0/53 (0%)
    Lymphocyte count decreased 4/139 (2.9%) 5/106 (4.7%) 2/53 (3.8%)
    Neutrophil count decreased 92/139 (66.2%) 69/106 (65.1%) 39/53 (73.6%)
    Platelet count decreased 45/139 (32.4%) 28/106 (26.4%) 9/53 (17%)
    Weight gain 0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    White blood cell decreased 50/139 (36%) 36/106 (34%) 24/53 (45.3%)
    Investigations - Other, specify 0/139 (0%) 1/106 (0.9%) 1/53 (1.9%)
    Metabolism and nutrition disorders
    Anorexia 0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Dehydration 1/139 (0.7%) 1/106 (0.9%) 0/53 (0%)
    Hyperglycemia 0/139 (0%) 0/106 (0%) 1/53 (1.9%)
    Hypocalcemia 1/139 (0.7%) 0/106 (0%) 0/53 (0%)
    Hypokalemia 1/139 (0.7%) 0/106 (0%) 0/53 (0%)
    Hypophosphatemia 1/139 (0.7%) 0/106 (0%) 0/53 (0%)
    Iron overload 0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Musculoskeletal and connective tissue disorders
    Arthritis 1/139 (0.7%) 0/106 (0%) 0/53 (0%)
    Chest wall pain 1/139 (0.7%) 0/106 (0%) 0/53 (0%)
    Myalgia 1/139 (0.7%) 0/106 (0%) 0/53 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Leukemia secondary to oncology chemo 2/139 (1.4%) 0/106 (0%) 0/53 (0%)
    Treatment related secondary malignancy 1/139 (0.7%) 0/106 (0%) 0/53 (0%)
    Neoplasms - Other 0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Nervous system disorders
    Ataxia 0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Dizziness 0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Peripheral motor neuropathy 1/139 (0.7%) 0/106 (0%) 0/53 (0%)
    Peripheral sensory neuropathy 1/139 (0.7%) 0/106 (0%) 1/53 (1.9%)
    Syncope 1/139 (0.7%) 0/106 (0%) 0/53 (0%)
    Renal and urinary disorders
    Acute kidney injury 0/139 (0%) 0/106 (0%) 1/53 (1.9%)
    Renal and urinary disorders - Other 0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnea 2/139 (1.4%) 4/106 (3.8%) 0/53 (0%)
    Pleural effusion 0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Respiratory thoracic mediastinal - Other 0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Skin and subcutaneous tissue disorders
    Pruritus 2/139 (1.4%) 1/106 (0.9%) 1/53 (1.9%)
    Rash maculo-papular 7/139 (5%) 3/106 (2.8%) 1/53 (1.9%)
    Skin ulceration 1/139 (0.7%) 0/106 (0%) 0/53 (0%)
    Vascular disorders
    Thromboembolic event 1/139 (0.7%) 0/106 (0%) 0/53 (0%)
    Other (Not Including Serious) Adverse Events
    Arm A (Step 1; Regardless of Chromosome 5q31.1 Status) Arm B (Step 1 Randomization; Lenalidomide + Epoetin Alfa) Arm B (Step 2 Cross-over; Lenalidomide + Epoetin Alfa)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 137/139 (98.6%) 105/106 (99.1%) 52/53 (98.1%)
    Blood and lymphatic system disorders
    Anemia 108/139 (77.7%) 92/106 (86.8%) 43/53 (81.1%)
    Gastrointestinal disorders
    Diarrhea 7/139 (5%) 3/106 (2.8%) 0/53 (0%)
    General disorders
    Fatigue 11/139 (7.9%) 10/106 (9.4%) 4/53 (7.5%)
    Investigations
    Creatinine increased 62/139 (44.6%) 50/106 (47.2%) 15/53 (28.3%)
    Neutrophil count decreased 99/139 (71.2%) 73/106 (68.9%) 43/53 (81.1%)
    Platelet count decreased 108/139 (77.7%) 77/106 (72.6%) 38/53 (71.7%)
    White blood cell decreased 114/139 (82%) 91/106 (85.8%) 47/53 (88.7%)
    Skin and subcutaneous tissue disorders
    Rash maculo-papular 9/139 (6.5%) 5/106 (4.7%) 0/53 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Study Statistician
    Organization ECOG-ACRIN Biostatistics Center
    Phone 617-632-3012
    Email eatrials@jimmy.harvard.edu
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00843882
    Other Study ID Numbers:
    • NCI-2009-01173
    • NCI-2009-01173
    • CDR0000634119
    • ECOG-E2905
    • 09-0095
    • E2905
    • E2905
    • E2905
    • U10CA180820
    • U10CA021115
    • U24CA196172
    First Posted:
    Feb 13, 2009
    Last Update Posted:
    Jul 28, 2022
    Last Verified:
    Jul 1, 2022