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 DiseaseIntervention/TreatmentPhase
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

ArmIntervention/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

    SiteCityStateCountryPostal Code
    1University of Alabama at Birmingham Cancer CenterBirminghamAlabamaUnited States35233
    2Alaska Breast Care and Surgery LLCAnchorageAlaskaUnited States99508
    3Alaska Women's Cancer CareAnchorageAlaskaUnited States99508
    4Anchorage Oncology CentreAnchorageAlaskaUnited States99508
    5Katmai Oncology GroupAnchorageAlaskaUnited States99508
    6Providence Alaska Medical CenterAnchorageAlaskaUnited States99508
    7Fairbanks Memorial HospitalFairbanksAlaskaUnited States99701
    8Mayo Clinic in ArizonaScottsdaleArizonaUnited States85259
    9Banner University Medical Center - TucsonTucsonArizonaUnited States85719
    10University of Arizona Cancer Center-North CampusTucsonArizonaUnited States85719
    11Kaiser Permanente-AnaheimAnaheimCaliforniaUnited States92806
    12Kaiser Permanente-Baldwin ParkBaldwin ParkCaliforniaUnited States91706
    13Kaiser Permanente-BellflowerBellflowerCaliforniaUnited States90706
    14Providence Saint Joseph Medical Center/Disney Family Cancer CenterBurbankCaliforniaUnited States91505
    15Kaiser Permanente-FontanaFontanaCaliforniaUnited States92335
    16Marin Cancer Care IncGreenbraeCaliforniaUnited States94904
    17Kaiser Permanente - Harbor CityHarbor CityCaliforniaUnited States90710
    18Kaiser Permanente-IrvineIrvineCaliforniaUnited States92618
    19Kaiser Permanente Los Angeles Medical CenterLos AngelesCaliforniaUnited States90027
    20Kaiser Permanente West Los AngelesLos AngelesCaliforniaUnited States90034
    21Fremont - Rideout Cancer CenterMarysvilleCaliforniaUnited States95901
    22Stanford Cancer Institute Palo AltoPalo AltoCaliforniaUnited States94304
    23Kaiser Permanente - Panorama CityPanorama CityCaliforniaUnited States91402
    24Kaiser Permanente-RiversideRiversideCaliforniaUnited States92505
    25University of California Davis Comprehensive Cancer CenterSacramentoCaliforniaUnited States95817
    26Saint Helena HospitalSaint HelenaCaliforniaUnited States94574
    27Kaiser Permanente-San Diego MissionSan DiegoCaliforniaUnited States92108
    28Kaiser Permanente-San Diego ZionSan DiegoCaliforniaUnited States92120
    29Kaiser Permanente-San MarcosSan MarcosCaliforniaUnited States92078
    30Presbyterian Intercommunity HospitalWhittierCaliforniaUnited States90602
    31Kaiser Permanente-Woodland HillsWoodland HillsCaliforniaUnited States91367
    32The Medical Center of AuroraAuroraColoradoUnited States80012
    33Boulder Community HospitalBoulderColoradoUnited States80301
    34Penrose-Saint Francis HealthcareColorado SpringsColoradoUnited States80907
    35Rocky Mountain Cancer Centers-PenroseColorado SpringsColoradoUnited States80907
    36Porter Adventist HospitalDenverColoradoUnited States80210
    37Colorado Blood Cancer InstituteDenverColoradoUnited States80218
    38Presbyterian - Saint Lukes Medical Center - Health OneDenverColoradoUnited States80218
    39Rocky Mountain Cancer Centers-MidtownDenverColoradoUnited States80218
    40SCL Health Saint Joseph HospitalDenverColoradoUnited States80218
    41Rocky Mountain Cancer Centers-RoseDenverColoradoUnited States80220
    42Rose Medical CenterDenverColoradoUnited States80220
    43Western States Cancer Research NCORPDenverColoradoUnited States80222
    44Mercy Medical CenterDurangoColoradoUnited States81301
    45Mountain Blue Cancer Care Center - SwedishEnglewoodColoradoUnited States80113
    46Swedish Medical CenterEnglewoodColoradoUnited States80113
    47Poudre Valley HospitalFort CollinsColoradoUnited States80524
    48Mountain Blue Cancer Care CenterGoldenColoradoUnited States80401
    49Saint Mary's Hospital and Regional Medical CenterGrand JunctionColoradoUnited States81501
    50North Colorado Medical CenterGreeleyColoradoUnited States80631
    51Rocky Mountain Cancer Centers-Greenwood VillageGreenwood VillageColoradoUnited States80111
    52Rocky Mountain Cancer Centers-LakewoodLakewoodColoradoUnited States80228
    53Saint Anthony HospitalLakewoodColoradoUnited States80228
    54Littleton Adventist HospitalLittletonColoradoUnited States80122
    55Rocky Mountain Cancer Centers-Sky RidgeLone TreeColoradoUnited States80124
    56Sky Ridge Medical CenterLone TreeColoradoUnited States80124
    57Longmont United HospitalLongmontColoradoUnited States80501
    58McKee Medical CenterLovelandColoradoUnited States80539
    59Parker Adventist HospitalParkerColoradoUnited States80138
    60Rocky Mountain Cancer Centers-ParkerParkerColoradoUnited States80138
    61Saint Mary Corwin Medical CenterPuebloColoradoUnited States81004
    62North Suburban Medical CenterThorntonColoradoUnited States80229
    63SCL Health Lutheran Medical CenterWheat RidgeColoradoUnited States80033
    64University of ConnecticutFarmingtonConnecticutUnited States06030
    65Smilow Cancer Hospital Care Center at Saint FrancisHartfordConnecticutUnited States06105
    66The Hospital of Central ConnecticutNew BritainConnecticutUnited States06050
    67Yale UniversityNew HavenConnecticutUnited States06520
    68Beebe Medical CenterLewesDelawareUnited States19958
    69Delaware Clinical and Laboratory Physicians PANewarkDelawareUnited States19713
    70Helen F Graham Cancer CenterNewarkDelawareUnited States19713
    71Medical Oncology Hematology Consultants PANewarkDelawareUnited States19713
    72Christiana Care Health System-Christiana HospitalNewarkDelawareUnited States19718
    73Beebe Health CampusRehoboth BeachDelawareUnited States19971
    74TidalHealth Nanticoke / Allen Cancer CenterSeafordDelawareUnited States19973
    75Holy Cross HospitalFort LauderdaleFloridaUnited States33308
    76Memorial Regional Hospital/Joe DiMaggio Children's HospitalHollywoodFloridaUnited States33021
    77Baptist MD Anderson Cancer CenterJacksonvilleFloridaUnited States32207
    78Mayo Clinic in FloridaJacksonvilleFloridaUnited States32224-9980
    79Jupiter Medical CenterJupiterFloridaUnited States33458
    80Leesburg Regional Medical CenterLeesburgFloridaUnited States34748
    81Mount Sinai Medical CenterMiami BeachFloridaUnited States33140
    82University of Miami Miller School of Medicine-Sylvester Cancer CenterMiamiFloridaUnited States33136
    83Miami Cancer InstituteMiamiFloridaUnited States33176
    84Moffitt Cancer CenterTampaFloridaUnited States33612
    85Augusta University Medical CenterAugustaGeorgiaUnited States30912
    86Saint Alphonsus Cancer Care Center-BoiseBoiseIdahoUnited States83706
    87Saint Luke's Cancer Institute - BoiseBoiseIdahoUnited States83712
    88Saint Luke's Cancer Institute - FruitlandFruitlandIdahoUnited States83619
    89Saint Luke's Cancer Institute - MeridianMeridianIdahoUnited States83642
    90Saint Luke's Cancer Institute - NampaNampaIdahoUnited States83686
    91Kootenai Clinic Cancer Services - Post FallsPost FallsIdahoUnited States83854
    92Saint Luke's Cancer Institute - Twin FallsTwin FallsIdahoUnited States83301
    93Illinois CancerCare-BloomingtonBloomingtonIllinoisUnited States61704
    94Illinois CancerCare-CantonCantonIllinoisUnited States61520
    95Illinois CancerCare-CarthageCarthageIllinoisUnited States62321
    96Hematology and Oncology AssociatesChicagoIllinoisUnited States60611
    97Northwestern UniversityChicagoIllinoisUnited States60611
    98Presence Resurrection Medical CenterChicagoIllinoisUnited States60631
    99University of Chicago Comprehensive Cancer CenterChicagoIllinoisUnited States60637
    100Weiss Memorial HospitalChicagoIllinoisUnited States60640
    101Carle on VermilionDanvilleIllinoisUnited States61832
    102Cancer Care Specialists of Illinois - DecaturDecaturIllinoisUnited States62526
    103Decatur Memorial HospitalDecaturIllinoisUnited States62526
    104Carle Physician Group-EffinghamEffinghamIllinoisUnited States62401
    105Crossroads Cancer CenterEffinghamIllinoisUnited States62401
    106Elmhurst Memorial HospitalElmhurstIllinoisUnited States60126
    107Illinois CancerCare-EurekaEurekaIllinoisUnited States61530
    108NorthShore University HealthSystem-Evanston HospitalEvanstonIllinoisUnited States60201
    109Saint Francis HospitalEvanstonIllinoisUnited States60202
    110Illinois CancerCare-GalesburgGalesburgIllinoisUnited States61401
    111NorthShore University HealthSystem-Glenbrook HospitalGlenviewIllinoisUnited States60026
    112Hematology Oncology Associates of Illinois-Highland ParkHighland ParkIllinoisUnited States60035
    113NorthShore University HealthSystem-Highland Park HospitalHighland ParkIllinoisUnited States60035
    114Midwest Center for Hematology OncologyJolietIllinoisUnited States60432
    115Duly Health and Care JolietJolietIllinoisUnited States60435
    116Presence Saint Mary's HospitalKankakeeIllinoisUnited States60901
    117Illinois CancerCare-Kewanee ClinicKewaneeIllinoisUnited States61443
    118AMG Libertyville - OncologyLibertyvilleIllinoisUnited States60048
    119Illinois CancerCare-MacombMacombIllinoisUnited States61455
    120Carle Physician Group-Mattoon/CharlestonMattoonIllinoisUnited States61938
    121Illinois Cancer Specialists-NilesNilesIllinoisUnited States60714
    122Cancer Care Center of O'FallonO'FallonIllinoisUnited States62269
    123Illinois CancerCare-Ottawa ClinicOttawaIllinoisUnited States61350
    124Illinois CancerCare-PekinPekinIllinoisUnited States61554
    125Illinois CancerCare-PeoriaPeoriaIllinoisUnited States61615
    126Illinois CancerCare-PeruPeruIllinoisUnited States61354
    127Illinois CancerCare-PrincetonPrincetonIllinoisUnited States61356
    128Swedish American HospitalRockfordIllinoisUnited States61104
    129SwedishAmerican Regional Cancer Center/ACTRockfordIllinoisUnited States61114
    130Hematology Oncology Associates of Illinois - SkokieSkokieIllinoisUnited States60076
    131Central Illinois Hematology Oncology CenterSpringfieldIllinoisUnited States62702
    132Southern Illinois University School of MedicineSpringfieldIllinoisUnited States62702
    133Springfield ClinicSpringfieldIllinoisUnited States62702
    134Memorial Medical CenterSpringfieldIllinoisUnited States62781
    135Carle Cancer CenterUrbanaIllinoisUnited States61801
    136The Carle Foundation HospitalUrbanaIllinoisUnited States61801
    137Northwestern Medicine Cancer Center WarrenvilleWarrenvilleIllinoisUnited States60555
    138Franciscan Saint Francis Health-Beech GroveBeech GroveIndianaUnited States46107
    139Elkhart ClinicElkhartIndianaUnited States46514-2098
    140Michiana Hematology Oncology PC-ElkhartElkhartIndianaUnited States46514
    141Elkhart General HospitalElkhartIndianaUnited States46515
    142Fort Wayne Medical Oncology and Hematology Inc-ParkviewFort WayneIndianaUnited States46845
    143IU Health Central Indiana Cancer Centers-EastIndianapolisIndianaUnited States46219
    144Community Howard Regional HealthKokomoIndianaUnited States46904
    145IU Health La Porte HospitalLa PorteIndianaUnited States46350
    146IU Health Arnett Cancer CareLafayetteIndianaUnited States47904
    147Premier Oncology Hematology AssociatesMerrillvilleIndianaUnited States46410
    148Memorial Regional Cancer Center Day RoadMishawakaIndianaUnited States46545
    149Michiana Hematology Oncology PC-MishawakaMishawakaIndianaUnited States46545
    150Saint Joseph Regional Medical Center-MishawakaMishawakaIndianaUnited States46545
    151Michiana Hematology Oncology PC-PlymouthPlymouthIndianaUnited States46563
    152Reid HealthRichmondIndianaUnited States47374
    153Memorial Hospital of South BendSouth BendIndianaUnited States46601
    154Michiana Hematology Oncology PC-South BendSouth BendIndianaUnited States46601
    155South Bend ClinicSouth BendIndianaUnited States46617
    156Northern Indiana Cancer Research ConsortiumSouth BendIndianaUnited States46628
    157Michiana Hematology Oncology PC-WestvilleWestvilleIndianaUnited States46391
    158McFarland Clinic PC - AmesAmesIowaUnited States50010
    159Mercy HospitalCedar RapidsIowaUnited States52403
    160Oncology Associates at Mercy Medical CenterCedar RapidsIowaUnited States52403
    161Medical Oncology and Hematology Associates-West Des MoinesCliveIowaUnited States50325
    162Mercy Cancer Center-West LakesCliveIowaUnited States50325
    163Mercy CapitolDes MoinesIowaUnited States50307
    164Iowa Methodist Medical CenterDes MoinesIowaUnited States50309
    165Iowa-Wide Oncology Research Coalition NCORPDes MoinesIowaUnited States50309
    166Medical Oncology and Hematology Associates-Des MoinesDes MoinesIowaUnited States50309
    167Medical Oncology and Hematology Associates-LaurelDes MoinesIowaUnited States50314
    168Mercy Medical Center - Des MoinesDes MoinesIowaUnited States50314
    169Iowa Lutheran HospitalDes MoinesIowaUnited States50316
    170Mercy Medical Center - North IowaMason CityIowaUnited States50401
    171Ottumwa Regional Health CenterOttumwaIowaUnited States52501
    172Siouxland Regional Cancer CenterSioux CityIowaUnited States51101
    173Mercy Medical Center-Sioux CitySioux CityIowaUnited States51102
    174Saint Luke's Regional Medical CenterSioux CityIowaUnited States51104
    175Mercy Medical Center-West LakesWest Des MoinesIowaUnited States50266
    176Lawrence Memorial HospitalLawrenceKansasUnited States66044
    177Menorah Medical CenterOverland ParkKansasUnited States66209
    178Saint Luke's South HospitalOverland ParkKansasUnited States66213
    179Kansas City NCI Community Oncology Research ProgramPrairie VillageKansasUnited States66208
    180Advent Health - Shawnee Mission Medical CenterShawnee MissionKansasUnited States66204
    181Wesley Medical CenterWichitaKansasUnited States67214
    182King's Daughter's Medical CenterAshlandKentuckyUnited States41101
    183Flaget Memorial HospitalBardstownKentuckyUnited States40004
    184Jewish HospitalLouisvilleKentuckyUnited States40202
    185Jewish Hospital Medical Center NortheastLouisvilleKentuckyUnited States40245
    186University of Maryland/Greenebaum Cancer CenterBaltimoreMarylandUnited States21201
    187Saint Agnes HospitalBaltimoreMarylandUnited States21229
    188Johns Hopkins University/Sidney Kimmel Cancer CenterBaltimoreMarylandUnited States21287
    189Walter Reed National Military Medical CenterBethesdaMarylandUnited States20889-5600
    190Christiana Care - Union HospitalElktonMarylandUnited States21921
    191Frederick Memorial HospitalFrederickMarylandUnited States21701
    192Steward Saint Elizabeth's Medical CenterBrightonMassachusettsUnited States02135
    193Lahey Hospital and Medical CenterBurlingtonMassachusettsUnited States01805
    194Holy Family HospitalMethuenMassachusettsUnited States01844
    195UMass Memorial Medical Center - University CampusWorcesterMassachusettsUnited States01655
    196Bixby Medical CenterAdrianMichiganUnited States49221
    197Hickman Cancer CenterAdrianMichiganUnited States49221
    198Michigan Cancer Research Consortium NCORPAnn ArborMichiganUnited States48106
    199Saint Joseph Mercy HospitalAnn ArborMichiganUnited States48106
    200University of Michigan Comprehensive Cancer CenterAnn ArborMichiganUnited States48109
    201Beaumont Hospital - DearbornDearbornMichiganUnited States48124
    202Wayne State University/Karmanos Cancer InstituteDetroitMichiganUnited States48201
    203Henry Ford HospitalDetroitMichiganUnited States48202
    204Ascension Saint John HospitalDetroitMichiganUnited States48236
    205Green Bay Oncology - EscanabaEscanabaMichiganUnited States49829
    206Genesys Hurley Cancer InstituteFlintMichiganUnited States48503
    207Hurley Medical CenterFlintMichiganUnited States48503
    208Genesys Regional Medical Center-West Flint CampusFlintMichiganUnited States48532
    209Green Bay Oncology - Iron MountainIron MountainMichiganUnited States49801
    210Allegiance HealthJacksonMichiganUnited States49201
    211Bronson Methodist HospitalKalamazooMichiganUnited States49007
    212West Michigan Cancer CenterKalamazooMichiganUnited States49007
    213Borgess Medical CenterKalamazooMichiganUnited States49048
    214Sparrow HospitalLansingMichiganUnited States48912
    215Saint Mary Mercy HospitalLivoniaMichiganUnited States48154
    216UP Health System MarquetteMarquetteMichiganUnited States49855
    217Mercy Memorial HospitalMonroeMichiganUnited States48162
    218Toledo Clinic Cancer Centers-MonroeMonroeMichiganUnited States48162
    219Lakeland Hospital NilesNilesMichiganUnited States49120
    220Saint Joseph Mercy OaklandPontiacMichiganUnited States48341
    221Lake Huron Medical CenterPort HuronMichiganUnited States48060
    222Ascension Saint Mary's HospitalSaginawMichiganUnited States48601
    223Lakeland Medical Center Saint JosephSaint JosephMichiganUnited States49085
    224Marie Yeager Cancer CenterSaint JosephMichiganUnited States49085
    225Ascension Providence Hospitals - SouthfieldSouthfieldMichiganUnited States48075
    226William Beaumont Hospital - TroyTroyMichiganUnited States48085
    227Saint John Macomb-Oakland HospitalWarrenMichiganUnited States48093
    228Medini, Eitan MD (UIA Investigator)AlexandriaMinnesotaUnited States56308
    229Fairview Ridges HospitalBurnsvilleMinnesotaUnited States55337
    230Mercy HospitalCoon RapidsMinnesotaUnited States55433
    231Essentia Health Cancer CenterDuluthMinnesotaUnited States55805
    232Fairview Southdale HospitalEdinaMinnesotaUnited States55435
    233Lake Region Healthcare Corporation-Cancer CareFergus FallsMinnesotaUnited States56537
    234Unity HospitalFridleyMinnesotaUnited States55432
    235Hutchinson Area Health CareHutchinsonMinnesotaUnited States55350
    236Minnesota Oncology Hematology PA-MaplewoodMaplewoodMinnesotaUnited States55109
    237Saint John's Hospital - HealtheastMaplewoodMinnesotaUnited States55109
    238Abbott-Northwestern HospitalMinneapolisMinnesotaUnited States55407
    239Hennepin County Medical CenterMinneapolisMinnesotaUnited States55415
    240Minneapolis VA Medical CenterMinneapolisMinnesotaUnited States55417
    241Health Partners IncMinneapolisMinnesotaUnited States55454
    242North Memorial Medical Health CenterRobbinsdaleMinnesotaUnited States55422
    243Mayo Clinic in RochesterRochesterMinnesotaUnited States55905
    244Coborn Cancer Center at Saint Cloud HospitalSaint CloudMinnesotaUnited States56303
    245Saint Cloud HospitalSaint CloudMinnesotaUnited States56303
    246Metro Minnesota Community Oncology Research ConsortiumSaint Louis ParkMinnesotaUnited States55416
    247Park Nicollet Clinic - Saint Louis ParkSaint Louis ParkMinnesotaUnited States55416
    248Regions HospitalSaint PaulMinnesotaUnited States55101
    249United HospitalSaint PaulMinnesotaUnited States55102
    250Saint Francis Regional Medical CenterShakopeeMinnesotaUnited States55379
    251Lakeview HospitalStillwaterMinnesotaUnited States55082
    252Ridgeview Medical CenterWaconiaMinnesotaUnited States55387
    253Rice Memorial HospitalWillmarMinnesotaUnited States56201
    254Minnesota Oncology Hematology PA-WoodburyWoodburyMinnesotaUnited States55125
    255Keesler Medical CenterKeesler Air Force BaseMississippiUnited States39534
    256Singing River HospitalPascagoulaMississippiUnited States39581
    257Saint Francis Medical CenterCape GirardeauMissouriUnited States63703
    258Southeast Cancer CenterCape GirardeauMissouriUnited States63703
    259University of Missouri - Ellis FischelColumbiaMissouriUnited States65212
    260Capital Region Southwest CampusJefferson CityMissouriUnited States65109
    261Truman Medical CentersKansas CityMissouriUnited States64108
    262Saint Luke's Hospital of Kansas CityKansas CityMissouriUnited States64111
    263Saint Joseph Health CenterKansas CityMissouriUnited States64114
    264North Kansas City HospitalKansas CityMissouriUnited States64116
    265Heartland Hematology and Oncology Associates IncorporatedKansas CityMissouriUnited States64118
    266Kansas City Veterans Affairs Medical CenterKansas CityMissouriUnited States64128
    267Research Medical CenterKansas CityMissouriUnited States64132
    268Saint Luke's East - Lee's SummitLee's SummitMissouriUnited States64086
    269Liberty Radiation Oncology CenterLibertyMissouriUnited States64068
    270Heartland Regional Medical CenterSaint JosephMissouriUnited States64506
    271Saint Joseph Oncology IncSaint JosephMissouriUnited States64507
    272Mercy Hospital SouthSaint LouisMissouriUnited States63128
    273Missouri Baptist Medical CenterSaint LouisMissouriUnited States63131
    274Center for Cancer Care and ResearchSaint LouisMissouriUnited States63141
    275Comprehensive Cancer Care PCSaint LouisMissouriUnited States63141
    276Mercy Hospital SpringfieldSpringfieldMissouriUnited States65804
    277Billings Clinic Cancer CenterBillingsMontanaUnited States59101
    278Northern Rockies Radiation Oncology CenterBillingsMontanaUnited States59101
    279Saint Vincent HealthcareBillingsMontanaUnited States59101
    280Montana Cancer Consortium NCORPBillingsMontanaUnited States59102
    281Saint Vincent Frontier Cancer CenterBillingsMontanaUnited States59102
    282Bozeman Deaconess HospitalBozemanMontanaUnited States59715
    283Saint James Community Hospital and Cancer Treatment CenterButteMontanaUnited States59701
    284Benefis Healthcare- Sletten Cancer InstituteGreat FallsMontanaUnited States59405
    285Berdeaux, Donald MD (UIA Investigator)Great FallsMontanaUnited States59405
    286Great Falls ClinicGreat FallsMontanaUnited States59405
    287Northern Montana HospitalHavreMontanaUnited States59501
    288Saint Peter's Community HospitalHelenaMontanaUnited States59601
    289Glacier Oncology PLLCKalispellMontanaUnited States59901
    290Kalispell Medical OncologyKalispellMontanaUnited States59901
    291Kalispell Regional Medical CenterKalispellMontanaUnited States59901
    292Montana Cancer SpecialistsMissoulaMontanaUnited States59802
    293Saint Patrick Hospital - Community HospitalMissoulaMontanaUnited States59802
    294Community Medical HospitalMissoulaMontanaUnited States59804
    295Guardian Oncology and Center for WellnessMissoulaMontanaUnited States59804
    296CHI Health Saint FrancisGrand IslandNebraskaUnited States68803
    297CHI Health Good SamaritanKearneyNebraskaUnited States68847
    298Nebraska Cancer Research CenterLincolnNebraskaUnited States68510
    299Missouri Valley Cancer ConsortiumOmahaNebraskaUnited States68106
    300Alegent Health Immanuel Medical CenterOmahaNebraskaUnited States68122
    301Alegent Health Bergan Mercy Medical CenterOmahaNebraskaUnited States68124
    302Creighton University Medical CenterOmahaNebraskaUnited States68131
    303University of Nebraska Medical CenterOmahaNebraskaUnited States68198
    304University Medical Center of Southern NevadaLas VegasNevadaUnited States89102
    305Summerlin Hospital Medical CenterLas VegasNevadaUnited States89144
    306OptumCare Cancer Care at Fort ApacheLas VegasNevadaUnited States89148
    307Nevada Cancer Research Foundation NCORPLas VegasNevadaUnited States89169
    308Cheshire Medical Center-Dartmouth-Hitchcock KeeneKeeneNew HampshireUnited States03431
    309Cooper Hospital University Medical CenterCamdenNew JerseyUnited States08103
    310Veterans Adminstration New Jersey Health Care SystemEast OrangeNew JerseyUnited States07018-1095
    311Virtua MemorialMount HollyNew JerseyUnited States08060
    312Inspira Medical Center Mullica HillMullica HillNew JerseyUnited States08062
    313Jersey Shore Medical CenterNeptuneNew JerseyUnited States07753
    314Newark Beth Israel Medical CenterNewarkNew JerseyUnited States07112
    315Riverview Medical Center/Booker Cancer CenterRed BankNew JerseyUnited States07701
    316Community Medical CenterToms RiverNew JerseyUnited States08755
    317Inspira Medical Center VinelandVinelandNew JerseyUnited States08360
    318Virtua VoorheesVoorheesNew JerseyUnited States08043
    319Montefiore Medical Center-Weiler HospitalBronxNew YorkUnited States10461
    320Montefiore Medical Center - Moses CampusBronxNew YorkUnited States10467
    321Hematology Oncology Associates of Central New York-East SyracuseEast SyracuseNew YorkUnited States13057
    322Glens Falls HospitalGlens FallsNew YorkUnited States12801
    323Garnet Health Medical CenterMiddletownNew YorkUnited States10940
    324NYU Winthrop HospitalMineolaNew YorkUnited States11501
    325Laura and Isaac Perlmutter Cancer Center at NYU LangoneNew YorkNew YorkUnited States10016
    326Memorial Sloan Kettering Cancer CenterNew YorkNew YorkUnited States10065
    327Highland HospitalRochesterNew YorkUnited States14620
    328University of RochesterRochesterNew YorkUnited States14642
    329State University of New York Upstate Medical UniversitySyracuseNew YorkUnited States13210
    330Mission HospitalAshevilleNorth CarolinaUnited States28801
    331Southeastern Medical Oncology Center-ClintonClintonNorth CarolinaUnited States28328
    332Southeastern Medical Oncology Center-GoldsboroGoldsboroNorth CarolinaUnited States27534
    333Wayne Memorial HospitalGoldsboroNorth CarolinaUnited States27534
    334Southeastern Medical Oncology Center-JacksonvilleJacksonvilleNorth CarolinaUnited States28546
    335Rex Cancer CenterRaleighNorth CarolinaUnited States27607
    336Rex Cancer Center of WakefieldRaleighNorth CarolinaUnited States27614
    337Iredell Memorial HospitalStatesvilleNorth CarolinaUnited States28677
    338Wake Forest University Health SciencesWinston-SalemNorth CarolinaUnited States27157
    339Mid Dakota ClinicBismarckNorth DakotaUnited States58501
    340Saint Alexius Medical CenterBismarckNorth DakotaUnited States58501
    341Sanford Bismarck Medical CenterBismarckNorth DakotaUnited States58501
    342Toledo Clinic Cancer Centers-Bowling GreenBowling GreenOhioUnited States43402
    343Cleveland Clinic Mercy HospitalCantonOhioUnited States44708
    344Aultman Health FoundationCantonOhioUnited States44710
    345Good Samaritan Hospital - CincinnatiCincinnatiOhioUnited States45220
    346TriHealth Cancer Institute-WestsideCincinnatiOhioUnited States45247
    347TriHealth Cancer Institute-AndersonCincinnatiOhioUnited States45255
    348Case Western Reserve UniversityClevelandOhioUnited States44106
    349MetroHealth Medical CenterClevelandOhioUnited States44109
    350North Coast Cancer Care-ClydeClydeOhioUnited States43410
    351Grandview HospitalDaytonOhioUnited States45405
    352Good Samaritan Hospital - DaytonDaytonOhioUnited States45406
    353Miami Valley HospitalDaytonOhioUnited States45409
    354Miami Valley Hospital NorthDaytonOhioUnited States45415
    355Dayton NCI Community Oncology Research ProgramDaytonOhioUnited States45459
    356Hematology Oncology Center IncorporatedElyriaOhioUnited States44035
    357Mercy Cancer Center-ElyriaElyriaOhioUnited States44035
    358Blanchard Valley HospitalFindlayOhioUnited States45840
    359Atrium Medical Center-Middletown Regional HospitalFranklinOhioUnited States45005-1066
    360Wayne HospitalGreenvilleOhioUnited States45331
    361Kettering Medical CenterKetteringOhioUnited States45429
    362Saint Rita's Medical CenterLimaOhioUnited States45801
    363Lima Memorial HospitalLimaOhioUnited States45804
    364Saint Luke's HospitalMaumeeOhioUnited States43537
    365Toledo Clinic Cancer Centers-MaumeeMaumeeOhioUnited States43537
    366Toledo Radiation Oncology at Northwest Ohio Onocolgy CenterMaumeeOhioUnited States43537
    367Fisher-Titus Medical CenterNorwalkOhioUnited States44857
    368Saint Charles HospitalOregonOhioUnited States43616
    369Toledo Clinic Cancer Centers-OregonOregonOhioUnited States43616
    370North Coast Cancer CareSanduskyOhioUnited States44870
    371ProMedica Flower HospitalSylvaniaOhioUnited States43560
    372Mercy Hospital of TiffinTiffinOhioUnited States44883
    373ProMedica Toledo Hospital/Russell J Ebeid Children's HospitalToledoOhioUnited States43606
    374Saint Vincent Mercy Medical CenterToledoOhioUnited States43608
    375University of ToledoToledoOhioUnited States43614
    376Toledo Community Hospital Oncology Program CCOPToledoOhioUnited States43617
    377Mercy Health - Saint Anne HospitalToledoOhioUnited States43623
    378Toledo Clinic Cancer Centers-ToledoToledoOhioUnited States43623
    379Upper Valley Medical CenterTroyOhioUnited States45373
    380Fulton County Health CenterWauseonOhioUnited States43567
    381Clinton Memorial HospitalWilmingtonOhioUnited States45177
    382Greene Memorial HospitalXeniaOhioUnited States45385
    383University of Oklahoma Health Sciences CenterOklahoma CityOklahomaUnited States73104
    384Clackamas Radiation Oncology CenterClackamasOregonUnited States97015
    385Bay Area HospitalCoos BayOregonUnited States97420
    386Providence Newberg Medical CenterNewbergOregonUnited States97132
    387Providence Willamette Falls Medical CenterOregon CityOregonUnited States97045
    388Providence Portland Medical CenterPortlandOregonUnited States97213
    389Providence Saint Vincent Medical CenterPortlandOregonUnited States97225
    390Jefferson Abington HospitalAbingtonPennsylvaniaUnited States19001
    391Bryn Mawr HospitalBryn MawrPennsylvaniaUnited States19010
    392Butler Memorial HospitalButlerPennsylvaniaUnited States16001
    393Carlisle Regional Cancer CenterCarlislePennsylvaniaUnited States17015
    394Geisinger Medical CenterDanvillePennsylvaniaUnited States17822
    395Ephrata Cancer CenterEphrataPennsylvaniaUnited States17522
    396Ephrata Community HospitalEphrataPennsylvaniaUnited States17522
    397Adams Cancer CenterGettysburgPennsylvaniaUnited States17325
    398Cherry Tree Cancer CenterHanoverPennsylvaniaUnited States17331
    399Geisinger Medical Center-Cancer Center HazletonHazletonPennsylvaniaUnited States18201
    400Penn State Milton S Hershey Medical CenterHersheyPennsylvaniaUnited States17033-0850
    401Lewistown HospitalLewistownPennsylvaniaUnited States17044
    402Riddle Memorial HospitalMediaPennsylvaniaUnited States19063
    403Paoli Memorial HospitalPaoliPennsylvaniaUnited States19301
    404University of Pennsylvania/Abramson Cancer CenterPhiladelphiaPennsylvaniaUnited States19104
    405Pennsylvania HospitalPhiladelphiaPennsylvaniaUnited States19107
    406Phoenixville HospitalPhoenixvillePennsylvaniaUnited States19460
    407Pottstown HospitalPottstownPennsylvaniaUnited States19464
    408Penn State Health Saint Joseph Medical CenterReadingPennsylvaniaUnited States19605
    409Guthrie Medical Group PC-Robert Packer HospitalSayrePennsylvaniaUnited States18840
    410Geisinger Medical GroupState CollegePennsylvaniaUnited States16801
    411Mount Nittany Medical CenterState CollegePennsylvaniaUnited States16803
    412Chester County HospitalWest ChesterPennsylvaniaUnited States19380
    413Reading HospitalWest ReadingPennsylvaniaUnited States19611
    414Geisinger Wyoming Valley/Henry Cancer CenterWilkes-BarrePennsylvaniaUnited States18711
    415UPMC SusquehannaWilliamsportPennsylvaniaUnited States17701
    416Lankenau Medical CenterWynnewoodPennsylvaniaUnited States19096
    417WellSpan Health-York HospitalYorkPennsylvaniaUnited States17403
    418Prisma Health Cancer Institute - SpartanburgBoiling SpringsSouth CarolinaUnited States29316
    419Prisma Health Cancer Institute - EasleyEasleySouth CarolinaUnited States29640
    420Greenville Health System Cancer Institute-AndrewsGreenvilleSouth CarolinaUnited States29601
    421Saint Francis HospitalGreenvilleSouth CarolinaUnited States29601
    422Prisma Health Cancer Institute - ButternutGreenvilleSouth CarolinaUnited States29605
    423Prisma Health Cancer Institute - FarisGreenvilleSouth CarolinaUnited States29605
    424Prisma Health Greenville Memorial HospitalGreenvilleSouth CarolinaUnited States29605
    425Prisma Health Cancer Institute - EastsideGreenvilleSouth CarolinaUnited States29615
    426Self Regional HealthcareGreenwoodSouth CarolinaUnited States29646
    427Prisma Health Cancer Institute - GreerGreerSouth CarolinaUnited States29650
    428Prisma Health Cancer Institute - SenecaSenecaSouth CarolinaUnited States29672
    429Rapid City Regional HospitalRapid CitySouth DakotaUnited States57701
    430Avera Cancer InstituteSioux FallsSouth DakotaUnited States57105
    431Avera McKennan Hospital and University Health CenterSioux FallsSouth DakotaUnited States57117-5045
    432Thompson Cancer Survival CenterKnoxvilleTennesseeUnited States37916
    433The Don and Sybil Harrington Cancer CenterAmarilloTexasUnited States79106
    434University of Virginia Cancer CenterCharlottesvilleVirginiaUnited States22908
    435Danville Regional Medical CenterDanvilleVirginiaUnited States24541
    436Fredericksburg Oncology IncFredericksburgVirginiaUnited States22401
    437Sovah Health MartinsvilleMartinsvilleVirginiaUnited States24115
    438PeaceHealth Saint Joseph Medical CenterBellinghamWashingtonUnited States98225
    439Harrison HealthPartners Hematology and Oncology-BremertonBremertonWashingtonUnited States98310
    440Swedish Cancer Institute-EdmondsEdmondsWashingtonUnited States98026
    441Kadlec Clinic Hematology and OncologyKennewickWashingtonUnited States99336
    442EvergreenHealth Medical CenterKirklandWashingtonUnited States98033
    443PeaceHealth Saint John Medical CenterLongviewWashingtonUnited States98632
    444Skagit Valley HospitalMount VernonWashingtonUnited States98274
    445Harrison HealthPartners Hematology and Oncology-PoulsboPoulsboWashingtonUnited States98370
    446Virginia Mason Medical CenterSeattleWashingtonUnited States98101
    447Minor and James Medical PLLCSeattleWashingtonUnited States98104
    448Pacific Medical Center-First HillSeattleWashingtonUnited States98104
    449Swedish Medical Center-Ballard CampusSeattleWashingtonUnited States98107
    450Kaiser Permanente WashingtonSeattleWashingtonUnited States98112
    451Swedish Medical Center-First HillSeattleWashingtonUnited States98122-4307
    452University of Washington Medical Center - MontlakeSeattleWashingtonUnited States98195
    453Cancer Care Northwest - Spokane SouthSpokaneWashingtonUnited States99202
    454Evergreen Hematology and Oncology PSSpokaneWashingtonUnited States99218
    455PeaceHealth Southwest Medical CenterVancouverWashingtonUnited States98664
    456Wenatchee Valley Hospital and ClinicsWenatcheeWashingtonUnited States98801
    457West Virginia University Charleston DivisionCharlestonWest VirginiaUnited States25304
    458West Virginia University HealthcareMorgantownWest VirginiaUnited States26506
    459Camden Clark Medical CenterParkersburgWest VirginiaUnited States26101
    460Princeton Community HospitalPrincetonWest VirginiaUnited States24740
    461ThedaCare Regional Cancer CenterAppletonWisconsinUnited States54911
    462Aurora Cancer Care-Southern Lakes VLCCBurlingtonWisconsinUnited States53105
    463Marshfield Clinic-Chippewa CenterChippewa FallsWisconsinUnited States54729
    464Marshfield Clinic Cancer Center at Sacred HeartEau ClaireWisconsinUnited States54701
    465Aurora Health Care Germantown Health CenterGermantownWisconsinUnited States53022
    466Aurora Cancer Care-GraftonGraftonWisconsinUnited States53024
    467Green Bay Oncology at Saint Vincent HospitalGreen BayWisconsinUnited States54301-3526
    468Saint Vincent Hospital Cancer Center Green BayGreen BayWisconsinUnited States54301
    469Green Bay Oncology Limited at Saint Mary's HospitalGreen BayWisconsinUnited States54303
    470Saint Vincent Hospital Cancer Center at Saint Mary'sGreen BayWisconsinUnited States54303
    471Aurora BayCare Medical CenterGreen BayWisconsinUnited States54311
    472Mercyhealth Hospital and Cancer Center - JanesvilleJanesvilleWisconsinUnited States53548
    473UW Cancer Center Johnson CreekJohnson CreekWisconsinUnited States53038
    474Aurora Cancer Care-Kenosha SouthKenoshaWisconsinUnited States53142
    475Gundersen Lutheran Medical CenterLa CrosseWisconsinUnited States54601
    476Dean Hematology and Oncology ClinicMadisonWisconsinUnited States53717
    477University of Wisconsin Hospital and ClinicsMadisonWisconsinUnited States53792
    478Holy Family Memorial HospitalManitowocWisconsinUnited States54221
    479Aurora Bay Area Medical Group-MarinetteMarinetteWisconsinUnited States54143
    480Bay Area Medical CenterMarinetteWisconsinUnited States54143
    481Marshfield Medical Center-MarshfieldMarshfieldWisconsinUnited States54449
    482Marshfield Medical CenterMarshfieldWisconsinUnited States54449
    483Aurora Cancer Care-MilwaukeeMilwaukeeWisconsinUnited States53209
    484Aurora Saint Luke's Medical CenterMilwaukeeWisconsinUnited States53215
    485Medical College of WisconsinMilwaukeeWisconsinUnited States53226
    486Aurora Sinai Medical CenterMilwaukeeWisconsinUnited States53233
    487Marshfield Clinic-Minocqua CenterMinocquaWisconsinUnited States54548
    488ProHealth D N Greenwald CenterMukwonagoWisconsinUnited States53149
    489Cancer Center of Western WisconsinNew RichmondWisconsinUnited States54017
    490ProHealth Oconomowoc Memorial HospitalOconomowocWisconsinUnited States53066
    491Saint Vincent Hospital Cancer Center at Oconto FallsOconto FallsWisconsinUnited States54154
    492Vince Lombardi Cancer Clinic - OshkoshOshkoshWisconsinUnited States54904
    493Aurora Cancer Care-RacineRacineWisconsinUnited States53406
    494Ascension Saint Mary's HospitalRhinelanderWisconsinUnited States54501
    495Marshfield Medical Center-Rice LakeRice LakeWisconsinUnited States54868
    496HSHS Saint Nicholas HospitalSheboyganWisconsinUnited States53081
    497Vince Lombardi Cancer Clinic-SheboyganSheboyganWisconsinUnited States53081
    498Ascension Saint Michael's HospitalStevens PointWisconsinUnited States54481
    499Saint Vincent Hospital Cancer Center at Sturgeon BaySturgeon BayWisconsinUnited States54235-1495
    500Green Bay Oncology - Sturgeon BaySturgeon BayWisconsinUnited States54235
    501Aurora Medical Center in SummitSummitWisconsinUnited States53066
    502Vince Lombardi Cancer Clinic-Two RiversTwo RiversWisconsinUnited States54241
    503Aurora Cancer Care-WaukeshaWaukeshaWisconsinUnited States53188
    504ProHealth Waukesha Memorial HospitalWaukeshaWisconsinUnited States53188
    505UW Cancer Center at ProHealth CareWaukeshaWisconsinUnited States53188
    506Aspirus Regional Cancer CenterWausauWisconsinUnited States54401
    507Aurora Cancer Care-Milwaukee WestWauwatosaWisconsinUnited States53226
    508Aurora West Allis Medical CenterWest AllisWisconsinUnited States53227
    509Marshfield Medical Center - WestonWestonWisconsinUnited States54476
    510Aspirus Cancer Care - Wisconsin RapidsWisconsin RapidsWisconsinUnited States54494
    511Marshfield Clinic - Wisconsin Rapids CenterWisconsin RapidsWisconsinUnited States54494
    512Rocky Mountain OncologyCasperWyomingUnited States82609
    513Welch Cancer CenterSheridanWyomingUnited States82801

    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:
    Sep 28, 2021
    Last Verified:
    Jul 1, 2021

    Study Results

    Participant Flow

    Recruitment DetailsFrom January 2009 through May 2016, the trial enrolled a total of 247 patients.
    Pre-assignment Detail
    Arm/Group TitleArm A (Lenalidomide; Chromosome 5q31.1 Deletion)Arm A (Lenalidomide; Randomization)Arm B (Lenalidomide + Epoetin Alfa; Randomization)
    Arm/Group DescriptionPatients 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
    STARTED38103106
    Treated Patients36103106
    Evaluable Patients Included in Primary Analysis09699
    Patients With Cytogenetic Response Data Available05551
    COMPLETED64841
    NOT COMPLETED325565
    Period Title: Step 1
    STARTED7460
    Evaluable Patients Included in Primary Analysis7370
    COMPLETED3200
    NOT COMPLETED4260

    Baseline Characteristics

    Arm/Group TitleArm A (Lenalidomide; Chromosome 5q31.1 Deletion)Arm A (Lenalidomide; Randomization)Arm B (Lenalidomide + Epoetin Alfa; Randomization)Total
    Arm/Group DescriptionPatients 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 Participants38103106247
    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
    TitleProportion of Patients With Major Erythroid Response (MER)
    DescriptionMajor 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 FrameAssessed 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 TitleArm A (Lenalidomide; Randomization)Arm B (Lenalidomide + Epoetin Alfa; Randomization)
    Arm/Group DescriptionPatients receive lenalidomide PO QD on days 1-21.Patients receive lenalidomide PO QD on days 1-21 and epoetin alfa SC once weekly.
    Measure Participants9699
    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 Hypothesisp-Value0.004
    Comments
    MethodFisher Exact
    Comments
    2. Secondary Outcome
    TitleTime to Major Erythroid Response (MER)
    DescriptionTime 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 FrameAssessed 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 TitleArm A (Lenalidomide; Randomization)Arm B (Lenalidomide + Epoetin Alfa; Randomization)
    Arm/Group DescriptionPatients receive lenalidomide PO QD on days 1-21.Patients receive lenalidomide PO QD on days 1-21 and epoetin alfa SC once weekly.
    Measure Participants1128
    Median (Full Range) [months]
    3.6
    3.7
    3. Secondary Outcome
    TitleDuration of Major Erythroid Response (MER)
    DescriptionDuration 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 FrameAssessed 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 TitleArm A (Lenalidomide; Randomization)Arm B (Lenalidomide + Epoetin Alfa; Randomization)
    Arm/Group DescriptionPatients receive lenalidomide PO QD on days 1-21.Patients receive lenalidomide PO QD on days 1-21 and epoetin alfa SC once weekly.
    Measure Participants1128
    Median (95% Confidence Interval) [months]
    13
    23.8
    4. Secondary Outcome
    TitleProportion of Patients With Major Erythroid Response (MER) to Salvage Combination Therapy
    DescriptionMajor 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 FrameAssessed 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 TitleArm B (Lenalidomide + Epoetin Alfa; Crossover)
    Arm/Group DescriptionPatients receive lenalidomide PO QD on days 1-21 and epoetin alfa SC once weekly.
    Measure Participants44
    Number (95% Confidence Interval) [proportion of participants]
    0.25
    0.7%
    5. Secondary Outcome
    TitleProportion of Patients With Minor Erythroid Response
    DescriptionThe 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 FrameAssessed 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 TitleArm A (Lenalidomide; Randomization)Arm B (Lenalidomide + Epoetin Alfa; Randomization)
    Arm/Group DescriptionPatients receive lenalidomide PO QD on days 1-21.Patients receive lenalidomide PO QD on days 1-21 and epoetin alfa SC once weekly.
    Measure Participants9699
    Number (90% Confidence Interval) [proportion of participants]
    0.208
    0.5%
    0.182
    0.2%
    6. Secondary Outcome
    TitleProportion of Patients With Major Erythroid Response (MER) Among Those With Chromosome 5q31.1 Deletion
    DescriptionMajor 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 FrameAssessed 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 TitleArm A (Lenalidomide; Chromosome 5q31.1 Deletion)
    Arm/Group DescriptionPatients receive lenalidomide PO QD on days 1-21.
    Measure Participants38
    Number (95% Confidence Interval) [proportion of participants]
    0.632
    1.7%
    7. Secondary Outcome
    TitleProportion of Patients With Bone Marrow Response
    DescriptionBone 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 FrameAssessed at 16 weeks

    Outcome Measure Data

    Analysis Population Description
    Evaluable patients randomized to either arm A or arm B
    Arm/Group TitleArm A (Lenalidomide; Randomization)Arm B (Lenalidomide + Epoetin Alfa; Randomization)
    Arm/Group DescriptionPatients receive lenalidomide PO QD on days 1-21.Patients receive lenalidomide PO QD on days 1-21 and epoetin alfa SC once weekly.
    Measure Participants9699
    Number (90% Confidence Interval) [proportion of participants]
    0.01
    0%
    0.03
    0%
    8. Secondary Outcome
    TitleProportion of Patients With Cytogenetic Response
    DescriptionEvaluation 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 FrameAssessed 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 TitleArm A (Lenalidomide; Randomization)Arm B (Lenalidomide + Epoetin Alfa; Randomization)
    Arm/Group DescriptionPatients receive lenalidomide PO QD on days 1-21.Patients receive lenalidomide PO QD on days 1-21 and epoetin alfa SC once weekly.
    Measure Participants5551
    Number (95% Confidence Interval) [proportion of participants]
    0.07
    0.2%
    0.10
    0.1%
    9. Secondary Outcome
    TitleAssociation Between Major Erythroid Response and Cytogenetic Response
    DescriptionMajor 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 FrameAssessed 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 TitleMajor Erythroid ResponseNo Major Erythroid Response
    Arm/Group DescriptionPatients with major erythroid responsePatients without major erythroid response
    Measure Participants2383
    Cytogenetic response
    4
    10.5%
    5
    4.9%
    No cytogenetic response
    19
    50%
    78
    75.7%
    10. Secondary Outcome
    TitlePretreatment Endogenous Erythropoietin Level
    DescriptionPretreatment 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 FrameAssessed 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 TitleArm A Patients With Major Erythroid ResponseArm A Patients Without Major Erythroid Response
    Arm/Group DescriptionPatients 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 Participants36105
    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 Hypothesisp-Value0.0002
    Comments
    MethodWilcoxon (Mann-Whitney)
    Comments
    11. Other Pre-specified Outcome
    TitleThe Association Between CD45 Isoform Profile and ex Vivo Augmentation of STAT5 Phosphorylation by Lenalidomide
    DescriptionTo 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 FrameAssessed 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
    TitleRNA and Protein Expression Level of Cdc25C, PP2A and Their Phosphatase Substrates, Cdc2phospho-Tyr15 and Cdc25Cphospho-Ser216
    DescriptionTo characterize molecular targets relevant to lenalidomide cytotoxicity in del5q31.1 cells.
    Time FrameAssessed 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
    TitleProportion of Patients With Cryptic Chromosome 5q31.1 Deletions
    DescriptionTo 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 FrameAssessed 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 FrameAssessed 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 TitleArm 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 DescriptionPatients 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 (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total29/141 (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 (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total123/139 (88.5%) 98/106 (92.5%) 49/53 (92.5%)
    Blood and lymphatic system disorders
    Anemia80/139 (57.6%) 65/106 (61.3%) 30/53 (56.6%)
    Febrile neutropenia6/139 (4.3%) 4/106 (3.8%) 0/53 (0%)
    Cardiac disorders
    Acute coronary syndrome0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Atrial fibrillation2/139 (1.4%) 1/106 (0.9%) 0/53 (0%)
    Chest pain - cardiac0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Heart failure1/139 (0.7%) 1/106 (0.9%) 0/53 (0%)
    Left ventricular systolic dysfunction0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Myocardial infarction0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Cardiac disorders - Other, specify0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Eye disorders
    Optic nerve disorder0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Gastrointestinal disorders
    Abdominal pain1/139 (0.7%) 1/106 (0.9%) 0/53 (0%)
    Colitis1/139 (0.7%) 1/106 (0.9%) 0/53 (0%)
    Colonic obstruction1/139 (0.7%) 0/106 (0%) 0/53 (0%)
    Constipation0/139 (0%) 1/106 (0.9%) 1/53 (1.9%)
    Diarrhea4/139 (2.9%) 3/106 (2.8%) 1/53 (1.9%)
    Nausea0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Vomiting1/139 (0.7%) 1/106 (0.9%) 0/53 (0%)
    General disorders
    Edema limbs1/139 (0.7%) 1/106 (0.9%) 1/53 (1.9%)
    Fatigue4/139 (2.9%) 8/106 (7.5%) 2/53 (3.8%)
    Fever0/139 (0%) 2/106 (1.9%) 0/53 (0%)
    Multi-organ failure0/139 (0%) 0/106 (0%) 1/53 (1.9%)
    Non-cardiac chest pain1/139 (0.7%) 0/106 (0%) 0/53 (0%)
    Immune system disorders
    Anaphylaxis0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Immune system disorders - Other, specify0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Infections and infestations
    Bronchial infection1/139 (0.7%) 0/106 (0%) 0/53 (0%)
    Lung infection2/139 (1.4%) 2/106 (1.9%) 0/53 (0%)
    Sepsis1/139 (0.7%) 2/106 (1.9%) 0/53 (0%)
    Soft tissue infection1/139 (0.7%) 1/106 (0.9%) 0/53 (0%)
    Urinary tract infection0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Wound infection0/139 (0%) 0/106 (0%) 1/53 (1.9%)
    Infections and infestations - Other0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Investigations
    Blood bilirubin increased1/139 (0.7%) 1/106 (0.9%) 0/53 (0%)
    Creatinine increased3/139 (2.2%) 5/106 (4.7%) 1/53 (1.9%)
    Hemoglobin increased1/139 (0.7%) 0/106 (0%) 0/53 (0%)
    Lymphocyte count decreased4/139 (2.9%) 5/106 (4.7%) 2/53 (3.8%)
    Neutrophil count decreased92/139 (66.2%) 69/106 (65.1%) 39/53 (73.6%)
    Platelet count decreased45/139 (32.4%) 28/106 (26.4%) 9/53 (17%)
    Weight gain0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    White blood cell decreased50/139 (36%) 36/106 (34%) 24/53 (45.3%)
    Investigations - Other, specify0/139 (0%) 1/106 (0.9%) 1/53 (1.9%)
    Metabolism and nutrition disorders
    Anorexia0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Dehydration1/139 (0.7%) 1/106 (0.9%) 0/53 (0%)
    Hyperglycemia0/139 (0%) 0/106 (0%) 1/53 (1.9%)
    Hypocalcemia1/139 (0.7%) 0/106 (0%) 0/53 (0%)
    Hypokalemia1/139 (0.7%) 0/106 (0%) 0/53 (0%)
    Hypophosphatemia1/139 (0.7%) 0/106 (0%) 0/53 (0%)
    Iron overload0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Musculoskeletal and connective tissue disorders
    Arthritis1/139 (0.7%) 0/106 (0%) 0/53 (0%)
    Chest wall pain1/139 (0.7%) 0/106 (0%) 0/53 (0%)
    Myalgia1/139 (0.7%) 0/106 (0%) 0/53 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Leukemia secondary to oncology chemo2/139 (1.4%) 0/106 (0%) 0/53 (0%)
    Treatment related secondary malignancy1/139 (0.7%) 0/106 (0%) 0/53 (0%)
    Neoplasms - Other0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Nervous system disorders
    Ataxia0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Dizziness0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Peripheral motor neuropathy1/139 (0.7%) 0/106 (0%) 0/53 (0%)
    Peripheral sensory neuropathy1/139 (0.7%) 0/106 (0%) 1/53 (1.9%)
    Syncope1/139 (0.7%) 0/106 (0%) 0/53 (0%)
    Renal and urinary disorders
    Acute kidney injury0/139 (0%) 0/106 (0%) 1/53 (1.9%)
    Renal and urinary disorders - Other0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnea2/139 (1.4%) 4/106 (3.8%) 0/53 (0%)
    Pleural effusion0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Respiratory thoracic mediastinal - Other0/139 (0%) 1/106 (0.9%) 0/53 (0%)
    Skin and subcutaneous tissue disorders
    Pruritus2/139 (1.4%) 1/106 (0.9%) 1/53 (1.9%)
    Rash maculo-papular7/139 (5%) 3/106 (2.8%) 1/53 (1.9%)
    Skin ulceration1/139 (0.7%) 0/106 (0%) 0/53 (0%)
    Vascular disorders
    Thromboembolic event1/139 (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 (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total137/139 (98.6%) 105/106 (99.1%) 52/53 (98.1%)
    Blood and lymphatic system disorders
    Anemia108/139 (77.7%) 92/106 (86.8%) 43/53 (81.1%)
    Gastrointestinal disorders
    Diarrhea7/139 (5%) 3/106 (2.8%) 0/53 (0%)
    General disorders
    Fatigue11/139 (7.9%) 10/106 (9.4%) 4/53 (7.5%)
    Investigations
    Creatinine increased62/139 (44.6%) 50/106 (47.2%) 15/53 (28.3%)
    Neutrophil count decreased99/139 (71.2%) 73/106 (68.9%) 43/53 (81.1%)
    Platelet count decreased108/139 (77.7%) 77/106 (72.6%) 38/53 (71.7%)
    White blood cell decreased114/139 (82%) 91/106 (85.8%) 47/53 (88.7%)
    Skin and subcutaneous tissue disorders
    Rash maculo-papular9/139 (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/TitleStudy Statistician
    OrganizationECOG-ACRIN Biostatistics Center
    Phone617-632-3012
    Emaileatrials@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:
    Sep 28, 2021
    Last Verified:
    Jul 1, 2021