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Active, not recruitingNCT00843882Updated Oct 1, 2026Results posted

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

A Phase 3 interventional study of Bone Marrow Biopsy and Epoetin Alfa in Anemia, Chronic Myelomonocytic Leukemia and De Novo Myelodysplastic Syndrome, sponsored by National Cancer Institute (NCI). Active, not recruiting at 507 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-01.

Sponsored by National Cancer Institute (NCI) · Phase 3, Interventional, and Treatment

Updated Oct 1, 20261 site added1 site removedGo to Updates ↓
Phase
Phase 3
Study type
Interventional
Enrollment
247
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the detailed description

PRIMARY OBJECTIVE:

I. To compare the rate of major erythroid response (MER) between lenalidomide monotherapy and combined treatment of lenalidomide and epoetin alfa in erythropoietin non-responsive low-/intermediate-1 (Int-1)-risk myelodysplastic syndrome (MDS) patients or erythropoietin treatment naïve patients with low probability of erythropoietin benefit.

SECONDARY OBJECTIVES:

I. To compare the time to MER by treatment assignment. II. To evaluate the duration of MER by treatment assignment. III. To estimate the frequency of MER to salvage combination therapy in patients who fail to experience a MER with lenalidomide monotherapy.

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

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

VI. To evaluate the frequency of cytogenetic response and progression, and the relation between cytogenetic pattern and erythroid response.

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

VIII. To evaluate the relationship between erythroid response and laboratory correlates outlined below:

VIIIa. Pretreatment and on study endogenous erythropoietin level (Arm A). VIIIb. To evaluate the effect of CD45 isoform profile on lenalidomide enhancement of erythropoietin-induced STAT5 phosphorylation in CD71\^Hi erythroid precursors and the relationship to erythroid response.

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

VIIId. To evaluate the frequency of cryptic chromosome 5q31.1 deletions in patients with non-del5q31.1 MDS by array-based genomic scan, and to determine the relationship to hematologic response.

OUTLINE: Patients are randomized to 1 of 2 treatment arms. Patients with del 5q31.1 karyotype are assigned to Arm A.

ARM A: Patients receive lenalidomide orally (PO) once daily (QD) on days 1-21. Patients undergo bone marrow biopsy at screening and during follow-up. Patients undergo blood specimen collection on study.

ARM B: Patients receive lenalidomide PO QD on days 1-21 and epoetin alfa subcutaneously (SC) once weekly. Patients undergo bone marrow biopsy at screening and during follow-up. Patients undergo blood specimen collection on study.

In both arms, treatment repeats every 28 days for 4 cycles. Patients who achieve a major erythroid response (MER) may continue treatment beyond 4 cycles in the absence of disease progression, disease conversion to acute myeloid leukemia, or unacceptable toxicity. Patients in Arm A who fail to achieve MER or who achieve MER but relapse after 16 weeks of treatment with lenalidomide may crossover and receive treatment in Arm B.

After completion of study treatment, patients are followed up for 6 months.

02

Conditions studied

  • Anemia
  • Chronic Myelomonocytic Leukemia
  • De Novo Myelodysplastic Syndrome
  • Myelodysplastic Syndrome
03

In context

Anemia

1,733 studies on the registry are indexed under Anemia; 246 are open to participants now.

This study's enrollment of 247 is above the median of 94 across 1,291 interventional studies indexed under Anemia.

Browse Anemia studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.

Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Age >= 18 years
  • NOTE: Results of the bone marrow biopsy and aspirate as well as cytogenetics are mandatory to register subjects onto study, which are indispensable to determine International Prognostic Scoring System (IPSS) category needed for eligibility; please note that it is not necessary to wait for the week 16, week 32, or week bone marrow and cytogenetic results prior to starting the next cycle unless deemed necessary by the treating physician; one example of this exception can include if the subject shows signs of progression, such as increased peripheral blood blast percentage; at that juncture, the treating physician may prefer to await the results prior to starting a new cycle; if a cycle is started, and based on the bone marrow results it is felt by the treating physician that the subject should not continue on treatment, please be sure to note this information on the case report forms at end of treatment
  • Patient must have documented diagnosis of MDS lasting at least three months (MDS duration >= 3 months) according to World Health Organization (WHO) criteria or non-proliferative chronic myelomonocytic leukemia (CMML) (white blood cell [WBC] \< 12,000/mcL)
  • Patient must have International Prognostic Scoring System (IPSS) categories of low- or intermediate-1-risk disease; patients must have IPSS score determined by cytogenetic analysis prior to randomization; patients must have cytogenetic analysis done (to calculate IPSS); if the current bone marrow biopsy is a dry tap, patients with cytogenetic failure and \< 10% marrow blasts will be eligible; subjects with cytogenetic failure must have previous cytogenetic results (fluorescence in situ hybridization [FISH] is not a substitute) within the last 6 months post last type of MDS treatment (in this case, not referring to growth factors as type of MDS treatment)

  • Must have symptomatic anemia untransfused with hemoglobin \< 9.5 g/dL =\< 8 weeks prior to randomization or with red blood cells (RBC) transfusion dependence (i.e., >= 2 units/month) confirmed for =\< 8 weeks before randomization

    • NOTE: For non-transfusion dependent patients (i.e., receiving \< 2 units/4 weeks x 8 weeks pre-study) who receive periodic transfusions, the mean 8 week pre-transfusion hemoglobin should be used to determine protocol eligibility and response reference
    • For non-transfusion dependent patients, a minimum of 2 pre-transfusion or un-transfused hemoglobin values are required

  • Applies only for patients without the deletion 5q 31.1; patients must have failed treatment with an erythropoietic growth factor, or have a low probability of response to rhu-erythropoietin; patients with low probability of response to rhu-erythropoietin or prior erythropoietin failures are defined as follows:

    • Prior erythropoietin failure-requires a minimum trial of >= 40,000 units epoetin alfa/week x 8 weeks or equivalent dose of darbepoetin alfa for 8 weeks with failure to achieve transfusion independence in dependent patients or a failure to achieve a >= 2 g rise in hemoglobin sustained for >= 4 weeks in non-transfusion dependent patients
    • Low erythropoietin response profile-rhu-erythropoietin and epoetin alfa-naïve patients receiving >= 2U packed (p)RBC/month for a minimum of 8 weeks, and serum erythropoietin > 500 mU/mL in the 8 weeks prior to randomization for a hemoglobin \< 9.5 g/dL
  • Patients must be off all non-transfusion therapy for MDS for 28 days prior to initiation of study treatment, including all types of growth factors; patients may receive hydrocortisone prophylactically to prevent transfusion reactions
  • Patients must have a serum erythropoietin level documented before randomization and =\< 56 days before day 1 of study treatment; NOTE: hemoglobin must be \< 9.5 g/dL at time that serum erythropoietin is drawn
  • Effective contraception must be used by patients participating in lenalidomide therapy, and all patients must agree to counseling by a trained counselor every 28 days about pregnancy precautions and risks of fetal exposure; females of childbearing potential (FCBP) must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control: one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide, during lenalidomide therapy, during dose interruptions, and for at least 28 days following discontinuation of lenalidomide therapy; females of childbearing potential should be referred to a qualified provider of contraceptive methods, if needed; males receiving lenalidomide must agree to use a latex condom during any sexual contact with females of childbearing potential even if they have undergone a successful vasectomy
  • Platelet count >= 50,000/mcL (50 x 10\^9/L) without platelet transfusion (within 56 days prior to randomization)
  • Absolute neutrophil count (ANC) >= 500 cells/mcL (0.5 x 10\^9/L); hence ANC must be >= 500/mcL without myeloid growth factor support (within 56 days prior to randomization)
  • Serum creatinine =\< 1.5 times upper limit of normal (ULN) (within 56 days prior to randomization)
  • Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) or serum glutamate pyruvate transaminase (SGPT)/alanine aminotransferase (ALT) =\< 2.0 x ULN (within 56 days prior to randomization)
  • Serum total bilirubin \< 3.0 mg/dL (within 56 days prior to randomization)
  • Inclusion criteria for crossover registration from Arm A (lenalidomide alone) to Arm B (lenalidomide and epoetin alfa):
  • Patients must have completed 16 weeks of monotherapy with lenalidomide
  • Patients must show failure to achieve MER (major erythroid response) or have achieved MER but relapsed on Arm A

Exclusion criteria

Exclusion Criteria:

  • Patients must not have documented iron deficiency; all patients must have documented marrow iron stores; if marrow iron stain is not available, the transferrin saturation must be > 20% or a serum ferritin > 100 ng/mL
  • Women must not be pregnant or breastfeeding; females of childbearing potential must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10-14 days and again within 24 hours prior to starting cycle 1 of lenalidomide; a female of childbearing potential (FCBP) is any woman, regardless of whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months; FCBP must also agree to ongoing pregnancy testing)
  • Patients must not have prior therapy with lenalidomide
  • Patients must not have a diagnosis of uncontrolled seizure or uncontrolled hypertension
  • Patients must not have proliferative (WBC >= 12,000/mcL) chronic myelomonocytic leukemia (CMML); WBC must be \< 12,000/mcL
  • Patients must not have MDS secondary to treatment with radiotherapy, chemotherapy, and/or immunotherapy for malignant or autoimmune diseases
  • Prior thalidomide therapy is allowed, however, patients must not have prior >= grade-3 allergic reactions to thalidomide
  • Patients must not have prior history of desquamating rash from thalidomide at time of study entry
  • Patients must not have clinically significant anemia resulting from iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis, or gastrointestinal bleeding
  • Patients must not have used cytotoxic chemotherapeutic agents or experimental agents (agents that are not commercially available) for the treatment of MDS within 8 weeks of randomization
  • Patients must not have prior history of malignancy other than MDS (except basal cell or squamous skin cell carcinoma or carcinoma in situ of the cervix or breast) unless the subject has been confirmed free of disease for >= 3 years
  • Patients must not have any serious medical condition or any other unstable medical co-morbidity, or psychiatric illness that will prevent the subject from signing the informed consent form or will place the subject at unacceptable risk if he/she participates in the study
  • Patients must not have a history of thrombo-embolic events within 3 years prior to study randomization
  • Patients must not have known human immunodeficiency virus (HIV)-1 seropositivity because HIV can be an alternate cause of anemia.
  • Patients must not have a known allergic reaction to epoetin alfa (Procrit) or human serum albumin
  • Exclusion criteria for crossover registration from Arm A (lenalidomide alone) to Arm B (lenalidomide and epoetin alfa):
  • Patients must not have a limiting unresolved grade 3 or greater toxicity from lenalidomide monotherapy or drug intolerance preventing continuation of lenalidomide treatment
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
None (open label)
Enrollment
247 participants (actual)

Study arms

  • Active comparator
    Arm A (lenalidomide)

    Patients receive lenalidomide PO QD on days 1-21. Patients undergo bone marrow biopsy at screening and during follow-up. Patients undergo blood specimen collection on study.

    Procedure: Bone Marrow Biopsy · Other: Laboratory Biomarker Analysis · Drug: Lenalidomide

  • Experimental
    Arm B (lenalidomide, epoetin alfa)

    Patients receive lenalidomide PO QD on days 1-21 and epoetin alfa SC once weekly. Patients undergo bone marrow biopsy at screening and during follow-up. Patients undergo blood specimen collection on study.

    Procedure: Bone Marrow Biopsy · Biological: Epoetin Alfa · Other: Laboratory Biomarker Analysis · Drug: Lenalidomide

Interventions

  • ProcedureBone Marrow Biopsy

    Undergo bone marrow biopsy

    Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

  • BiologicalEpoetin Alfa

    Given SC

    Also known as: EPO, Epoetin alfa-epbx, Epogen, Eprex, Procrit, Retacrit

  • OtherLaboratory Biomarker Analysis

    Correlative studies

  • DrugLenalidomide

    Given PO

    Also known as: CC 5013, CC-5013, CC5013, CDC 501, Revlimid

06

What researchers measure

Primary outcomes

  1. Proportion of Patients With Major Erythroid Response (MER)

    Major erythroid response is defined as transfusion-independence for ≥ 8 consecutive weeks for patients who were red blood cell transfusion-dependent at baseline AND a ≥ 1 g/dL hemoglobin rise compared to mean pre-transfusion baseline value; or a \> 2 g/dL rise in hemoglobin without transfusion for non-transfusion dependent patients.

    Time frame: Assessed after completion of 16 weeks of treatment

Secondary outcomes

  1. Time to Major Erythroid Response (MER)

    Time to major erythroid response (MER) is defined in responders as the time from randomization to the documented date of MER. For transfusion independent patients, the date of MER is the first date of the elevation in hemoglobin level of more than 2 g/dL that has been sustained for at least 8 weeks. For transfusion dependent patients, the date of MER is the beginning date of the time interval of transfusion independence that has been sustained for at least eight weeks.

    Time frame: Assessed every cycle during treatment and then 3 and 6 months after last protocol treatment

  2. Duration of Major Erythroid Response (MER)

    Duration of major erythroid response (MER) is defined as the time interval between the documented date of MER and the earliest date of resumption of red blood cell transfusions ≥ 2 units in an 8-week period, a reduction in hemoglobin concentration ≥ 2 g/dL in the absence of acute infection, gastrointestinal bleeding and hemolysis, or death.

    Time frame: Assessed every cycle during treatment and then 3 and 6 months after last protocol treatment

  3. Proportion of Patients With Major Erythroid Response (MER) to Salvage Combination Therapy

    Major erythroid response is defined as transfusion-independence for ≥ 8 consecutive weeks for patients who were red blood cell transfusion-dependent at baseline AND a ≥ 1 g/dL hemoglobin rise compared to mean pre-transfusion baseline value; or a \> 2 g/dL rise in hemoglobin without transfusion for non-transfusion dependent patients.

    Time frame: Assessed after completion of 16 weeks of treatment

  4. Proportion of Patients With Minor Erythroid Response

    The definition of minor erythroid response: the mean hemoglobin is sustained 1.0 to 2.0 g/dL above the baseline value for a minimum of 8 weeks; or a 50% or greater decrease in 8-week red blood cell transfusion requirements compared to baseline.

    Time frame: Assessed every cycle during treatment and after completion of 16 weeks of treatment

  5. Proportion of Patients With Major Erythroid Response (MER) Among Those With Chromosome 5q31.1 Deletion

    Major erythroid response is defined as transfusion-independence for ≥ 8 consecutive weeks for patients who were red blood cell transfusion-dependent at baseline AND a ≥ 1 g/dL hemoglobin rise compared to mean pre-transfusion baseline value; or a \> 2 g/dL rise in hemoglobin without transfusion for non-transfusion dependent patients.

    Time frame: Assessed after completion of 16 weeks of treatment

  6. Proportion of Patients With Bone Marrow Response

    Bone marrow response includes complete remission (CR) and partial remission (PR). Complete remission (CR): Bone marrow showing \< 5% myeloblasts with normal maturation of all cell lines, with no evidence for dysplasia. When erythroid precursors constitute \< 50% of bone marrow nucleated cells, the percent of blasts is based on all nucleated cells; when there are ≥ 50% erythroid cells, the percent blasts should be based on the non-erythroid cells. Partial remission (PR): All of the CR criteria (if abnormal prior to treatment), except blasts decreased by 50% over pre-treatment, or a less advanced Myelodysplastic Syndromes (MDS) World Health Organization (WHO) classification than pretreatment. Cellularity and morphology are not relevant.

    Time frame: Assessed at 16 weeks

  7. Proportion of Patients With Cytogenetic Response

    Evaluation of cytogenetic response requires 20 analyzable metaphases when using conventional techniques. Analysis of data will require 20 metaphases before and after treatment, which must be done on bone marrow only (peripheral blood is not a substitute). Fluorescent in situ hybridization (FISH) may be used as a supplement to follow a specifically defined cytogenetic abnormality, but it is not a substitute for conventional cytogenetic studies. Cytogenetic response is defined as follows: Complete response: Restoration of a normal karyotype in patients with a documented pre-existing clonal (\>2 metaphases abnormal) chromosome abnormalities. Partial response: \> 50% reduction in the percentage of bone marrow metaphases with only clonal abnormality.

    Time frame: Assessed at baseline and after completion of 16 weeks of treatment

  8. Association Between Major Erythroid Response and Cytogenetic Response

    Major erythroid response is defined as transfusion-independence for ≥ 8 consecutive weeks for patients who were red blood cell transfusion-dependent at baseline AND a ≥ 1 g/dL hemoglobin rise compared to mean pre-transfusion baseline value; or a \> 2 g/dL rise in hemoglobin without transfusion for non-transfusion dependent patients. Evaluation of cytogenetic response requires 20 analyzable metaphases before and after treatment, which must be done on bone marrow only. Fluorescent in situ hybridization (FISH) may be used as a supplement to follow a specifically defined cytogenetic abnormality, but it is not a substitute for conventional cytogenetic studies. Cytogenetic response is defined as follows: Complete response: Restoration of a normal karyotype in patients with a documented pre-existing clonal (\>2 metaphases abnormal) chromosome abnormalities. Partial response: \> 50% reduction in the percentage of bone marrow metaphases with only clonal abnormality.

    Time frame: Assessed at baseline and after completion of 16 weeks of treatment

  9. Pretreatment Endogenous Erythropoietin Level

    Pretreatment endogenous erythropoietin level was assessed at baseline. The association between pretreatment endogenous erythropoietin level and major erythroid response was evaluated among patients who received lenalidomide alone. Major erythroid response is defined as transfusion-independence for ≥ 8 consecutive weeks for patients who were red blood cell transfusion-dependent at baseline AND a ≥ 1 g/dL hemoglobin rise compared to mean pre-transfusion baseline value; or a \> 2 g/dL rise in hemoglobin without transfusion for non-transfusion dependent patients.

    Time frame: Assessed at baseline and after completion of 16 weeks of treatment

Other outcomes

  1. The Association Between CD45 Isoform Profile and ex Vivo Augmentation of STAT5 Phosphorylation by Lenalidomide

    To evaluate the effect of CD45 isoform profile on lenalidomide enhancement of erythropoietin-induced STAT5 phosphorylation in CD71Hi erythroid precursors and the relationship to erythroid response.

    Time frame: Assessed at baseline and after completion of 16 weeks of treatment

  2. RNA and Protein Expression Level of Cdc25C, PP2A and Their Phosphatase Substrates, Cdc2phospho-Tyr15 and Cdc25Cphospho-Ser216

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

    Time frame: Assessed at baseline and after completion of 16 weeks of treatment

  3. Proportion of Patients With Cryptic Chromosome 5q31.1 Deletions

    To evaluate the frequency of cryptic chromosome 5q31.1 deletions in patients with non-del5q31.1 MDS by array based genomic scan, and to determine the relationship to hematologic response.

    Time frame: Assessed at baseline and after completion of 16 weeks of treatment

07

Results

Posted Jul 8, 2021

Participant flow

From April 2009 through May 2016, the trial enrolled a total of 247 patients.

Step 1
Participant flow — Step 1
MilestoneArm A (Lenalidomide; Chromosome 5q31.1 Deletion)Arm A (Lenalidomide; Randomization)Arm B (Lenalidomide + Epoetin Alfa; Randomization)
Started38103106
Treated patients36103106
Evaluable patients included in primary analysis09699
Patients with cytogenetic response data available05551
Completed64841
Not completed325565
Withdrew: Lack of efficacy141021
Withdrew: Adverse event81720
Withdrew: Death124
Withdrew: Withdrawal by subject6129
Withdrew: Physician decision051
Withdrew: Patient and physician's decision001
Withdrew: Other complicating disease134
Withdrew: Alternative therapy011
Withdrew: Patient switched treatment early due to dsmc announcement040
Withdrew: Off treatment reason unknown014
Withdrew: Never started treatment200
Step 2 (Cross-over to Arm B)
Participant flow — Step 2 (Cross-over to Arm B)
MilestoneArm A (Lenalidomide; Chromosome 5q31.1 Deletion)Arm A (Lenalidomide; Randomization)Arm B (Lenalidomide + Epoetin Alfa; Randomization)
Started7460
Evaluable patients included in primary analysis7370
Completed3200
Not completed4260
Withdrew: Lack of efficacy190
Withdrew: Adverse event060
Withdrew: Death030
Withdrew: Withdrawal by subject250
Withdrew: Physician decision110
Withdrew: Alternative treatment010
Withdrew: Prolonged wound healing010

Outcome measures

PrimaryProportion of Patients With Major Erythroid Response (MER)

Major erythroid response is defined as transfusion-independence for ≥ 8 consecutive weeks for patients who were red blood cell transfusion-dependent at baseline AND a ≥ 1 g/dL hemoglobin rise compared to mean pre-transfusion baseline value; or a \> 2 g/dL rise in hemoglobin without transfusion for non-transfusion dependent patients.

Time frame:
Assessed after completion of 16 weeks of treatment
Reported as:
Number · proportion of participants
Proportion of Patients With Major Erythroid Response (MER)
proportion of participantsArm A (Lenalidomide; Randomization)Arm B (Lenalidomide + Epoetin Alfa; Randomization)
Proportion of Patients With Major Erythroid Response (MER)0.115 (0.066 to 0.183)0.283 (0.209 to 0.367)
Statistical analysis
  • Arm A (Lenalidomide; Randomization) vs Arm B (Lenalidomide + Epoetin Alfa; Randomization) · Fisher Exact · p = 0.004
SecondaryTime to Major Erythroid Response (MER)

Time to major erythroid response (MER) is defined in responders as the time from randomization to the documented date of MER. For transfusion independent patients, the date of MER is the first date of the elevation in hemoglobin level of more than 2 g/dL that has been sustained for at least 8 weeks. For transfusion dependent patients, the date of MER is the beginning date of the time interval of transfusion independence that has been sustained for at least eight weeks.

Time frame:
Assessed every cycle during treatment and then 3 and 6 months after last protocol treatment
Reported as:
Median · months
Time to Major Erythroid Response (MER)
monthsArm A (Lenalidomide; Randomization)Arm B (Lenalidomide + Epoetin Alfa; Randomization)
Time to Major Erythroid Response (MER)3.6 (2.1 to 5.5)3.7 (1.0 to 10.6)
SecondaryDuration of Major Erythroid Response (MER)

Duration of major erythroid response (MER) is defined as the time interval between the documented date of MER and the earliest date of resumption of red blood cell transfusions ≥ 2 units in an 8-week period, a reduction in hemoglobin concentration ≥ 2 g/dL in the absence of acute infection, gastrointestinal bleeding and hemolysis, or death.

Time frame:
Assessed every cycle during treatment and then 3 and 6 months after last protocol treatment
Reported as:
Median · months
Duration of Major Erythroid Response (MER)
monthsArm A (Lenalidomide; Randomization)Arm B (Lenalidomide + Epoetin Alfa; Randomization)
Duration of Major Erythroid Response (MER)13 (2.1 to 75)23.8 (8.5 to NA)
SecondaryProportion of Patients With Major Erythroid Response (MER) to Salvage Combination Therapy

Major erythroid response is defined as transfusion-independence for ≥ 8 consecutive weeks for patients who were red blood cell transfusion-dependent at baseline AND a ≥ 1 g/dL hemoglobin rise compared to mean pre-transfusion baseline value; or a \> 2 g/dL rise in hemoglobin without transfusion for non-transfusion dependent patients.

Time frame:
Assessed after completion of 16 weeks of treatment
Reported as:
Number · proportion of participants
Proportion of Patients With Major Erythroid Response (MER) to Salvage Combination Therapy
proportion of participantsArm B (Lenalidomide + Epoetin Alfa; Crossover)
Proportion of Patients With Major Erythroid Response (MER) to Salvage Combination Therapy0.25 (0.13 to 0.40)
SecondaryProportion of Patients With Minor Erythroid Response

The definition of minor erythroid response: the mean hemoglobin is sustained 1.0 to 2.0 g/dL above the baseline value for a minimum of 8 weeks; or a 50% or greater decrease in 8-week red blood cell transfusion requirements compared to baseline.

Time frame:
Assessed every cycle during treatment and after completion of 16 weeks of treatment
Reported as:
Number · proportion of participants
Proportion of Patients With Minor Erythroid Response
proportion of participantsArm A (Lenalidomide; Randomization)Arm B (Lenalidomide + Epoetin Alfa; Randomization)
Proportion of Patients With Minor Erythroid Response0.208 (0.142 to 0.288)0.182 (0.121 to 0.258)
SecondaryProportion of Patients With Major Erythroid Response (MER) Among Those With Chromosome 5q31.1 Deletion

Major erythroid response is defined as transfusion-independence for ≥ 8 consecutive weeks for patients who were red blood cell transfusion-dependent at baseline AND a ≥ 1 g/dL hemoglobin rise compared to mean pre-transfusion baseline value; or a \> 2 g/dL rise in hemoglobin without transfusion for non-transfusion dependent patients.

Time frame:
Assessed after completion of 16 weeks of treatment
Reported as:
Number · proportion of participants
Proportion of Patients With Major Erythroid Response (MER) Among Those With Chromosome 5q31.1 Deletion
proportion of participantsArm A (Lenalidomide; Chromosome 5q31.1 Deletion)
Proportion of Patients With Major Erythroid Response (MER) Among Those With Chromosome 5q31.1 Deletion0.632 (0.46 to 0.782)
SecondaryProportion of Patients With Bone Marrow Response

Bone marrow response includes complete remission (CR) and partial remission (PR). Complete remission (CR): Bone marrow showing \< 5% myeloblasts with normal maturation of all cell lines, with no evidence for dysplasia. When erythroid precursors constitute \< 50% of bone marrow nucleated cells, the percent of blasts is based on all nucleated cells; when there are ≥ 50% erythroid cells, the percent blasts should be based on the non-erythroid cells. Partial remission (PR): All of the CR criteria (if abnormal prior to treatment), except blasts decreased by 50% over pre-treatment, or a less advanced Myelodysplastic Syndromes (MDS) World Health Organization (WHO) classification than pretreatment. Cellularity and morphology are not relevant.

Time frame:
Assessed at 16 weeks
Reported as:
Number · proportion of participants
Proportion of Patients With Bone Marrow Response
proportion of participantsArm A (Lenalidomide; Randomization)Arm B (Lenalidomide + Epoetin Alfa; Randomization)
Proportion of Patients With Bone Marrow Response0.01 (0.0006 to 0.049)0.03 (0.008 to 0.077)
SecondaryProportion of Patients With Cytogenetic Response

Evaluation of cytogenetic response requires 20 analyzable metaphases when using conventional techniques. Analysis of data will require 20 metaphases before and after treatment, which must be done on bone marrow only (peripheral blood is not a substitute). Fluorescent in situ hybridization (FISH) may be used as a supplement to follow a specifically defined cytogenetic abnormality, but it is not a substitute for conventional cytogenetic studies. Cytogenetic response is defined as follows: Complete response: Restoration of a normal karyotype in patients with a documented pre-existing clonal (\>2 metaphases abnormal) chromosome abnormalities. Partial response: \> 50% reduction in the percentage of bone marrow metaphases with only clonal abnormality.

Time frame:
Assessed at baseline and after completion of 16 weeks of treatment
Reported as:
Number · proportion of participants
Proportion of Patients With Cytogenetic Response
proportion of participantsArm A (Lenalidomide; Randomization)Arm B (Lenalidomide + Epoetin Alfa; Randomization)
Proportion of Patients With Cytogenetic Response0.07 (0.02 to 0.18)0.10 (0.03 to 0.21)
SecondaryAssociation Between Major Erythroid Response and Cytogenetic Response

Major erythroid response is defined as transfusion-independence for ≥ 8 consecutive weeks for patients who were red blood cell transfusion-dependent at baseline AND a ≥ 1 g/dL hemoglobin rise compared to mean pre-transfusion baseline value; or a \> 2 g/dL rise in hemoglobin without transfusion for non-transfusion dependent patients. Evaluation of cytogenetic response requires 20 analyzable metaphases before and after treatment, which must be done on bone marrow only. Fluorescent in situ hybridization (FISH) may be used as a supplement to follow a specifically defined cytogenetic abnormality, but it is not a substitute for conventional cytogenetic studies. Cytogenetic response is defined as follows: Complete response: Restoration of a normal karyotype in patients with a documented pre-existing clonal (\>2 metaphases abnormal) chromosome abnormalities. Partial response: \> 50% reduction in the percentage of bone marrow metaphases with only clonal abnormality.

Time frame:
Assessed at baseline and after completion of 16 weeks of treatment
Reported as:
Count of participants · Participants
Association Between Major Erythroid Response and Cytogenetic Response
ParticipantsMajor Erythroid ResponseNo Major Erythroid Response
Cytogenetic response45
No cytogenetic response1978
SecondaryPretreatment Endogenous Erythropoietin Level

Pretreatment endogenous erythropoietin level was assessed at baseline. The association between pretreatment endogenous erythropoietin level and major erythroid response was evaluated among patients who received lenalidomide alone. Major erythroid response is defined as transfusion-independence for ≥ 8 consecutive weeks for patients who were red blood cell transfusion-dependent at baseline AND a ≥ 1 g/dL hemoglobin rise compared to mean pre-transfusion baseline value; or a \> 2 g/dL rise in hemoglobin without transfusion for non-transfusion dependent patients.

Time frame:
Assessed at baseline and after completion of 16 weeks of treatment
Reported as:
Median · mU/mL
Pretreatment Endogenous Erythropoietin Level
mU/mLArm A Patients With Major Erythroid ResponseArm A Patients Without Major Erythroid Response
Pretreatment Endogenous Erythropoietin Level514.5 (82 to 3405)150 (11 to 3048)
Statistical analysis
  • Arm A Patients With Major Erythroid Response vs Arm A Patients Without Major Erythroid Response · Wilcoxon (Mann-Whitney) · p = 0.0002
Other pre-specifiedThe Association Between CD45 Isoform Profile and ex Vivo Augmentation of STAT5 Phosphorylation by Lenalidomide

To evaluate the effect of CD45 isoform profile on lenalidomide enhancement of erythropoietin-induced STAT5 phosphorylation in CD71Hi erythroid precursors and the relationship to erythroid response.

Time frame:
Assessed at baseline and after completion of 16 weeks of treatment

Results for this outcome have not been posted.

Other pre-specifiedRNA and Protein Expression Level of Cdc25C, PP2A and Their Phosphatase Substrates, Cdc2phospho-Tyr15 and Cdc25Cphospho-Ser216

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

Time frame:
Assessed at baseline and after completion of 16 weeks of treatment

Results for this outcome have not been posted.

Other pre-specifiedProportion of Patients With Cryptic Chromosome 5q31.1 Deletions

To evaluate the frequency of cryptic chromosome 5q31.1 deletions in patients with non-del5q31.1 MDS by array based genomic scan, and to determine the relationship to hematologic response.

Time frame:
Assessed at baseline and after completion of 16 weeks of treatment

Results for this outcome have not been posted.

Adverse events

Collected over Assessed every 4 weeks while on treatment and for 30 days after the end of treatment. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Arm A (Step 1; Regardless of Chromosome 5q31.1 Status)29/141 (20.6%)123/139 (88.5%)137/139 (98.6%)
Arm B (Step 1 Randomization; Lenalidomide + Epoetin Alfa)29/106 (27.4%)98/106 (92.5%)105/106 (99.1%)
Arm B (Step 2 Cross-over; Lenalidomide + Epoetin Alfa)0/53 (0%)49/53 (92.5%)52/53 (98.1%)
Most frequent serious events
Showing 10 of 67
Most frequent serious events
EventArm 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)
Neutrophil count decreasedInvestigations92/13969/10639/53
AnemiaBlood and lymphatic system disorders80/13965/10630/53
White blood cell decreasedInvestigations50/13936/10624/53
Platelet count decreasedInvestigations45/13928/1069/53
FatigueGeneral disorders4/1398/1062/53
Rash maculo-papularSkin and subcutaneous tissue disorders7/1393/1061/53
Creatinine increasedInvestigations3/1395/1061/53
Lymphocyte count decreasedInvestigations4/1395/1062/53
Febrile neutropeniaBlood and lymphatic system disorders6/1394/1060/53
DyspneaRespiratory, thoracic and mediastinal disorders2/1394/1060/53
Most frequent other events
Most frequent other events
EventArm 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)
White blood cell decreasedInvestigations114/13991/10647/53
AnemiaBlood and lymphatic system disorders108/13992/10643/53
Neutrophil count decreasedInvestigations99/13973/10643/53
Platelet count decreasedInvestigations108/13977/10638/53
Creatinine increasedInvestigations62/13950/10615/53
FatigueGeneral disorders11/13910/1064/53
Rash maculo-papularSkin and subcutaneous tissue disorders9/1395/1060/53
DiarrheaGastrointestinal disorders7/1393/1060/53

Baseline characteristics

All patients enrolled are included in this analysis.

Age, Continuous
Age, Continuous(years)Arm A (Lenalidomide; Chromosome 5q31.1 Deletion)Arm A (Lenalidomide; Randomization)Arm B (Lenalidomide + Epoetin Alfa; Randomization)Total
Median77 (62 to 88)74 (49 to 89)73 (47 to 92)74 (47 to 92)
Sex: Female, Male
Sex: Female, Male(Participants)Arm A (Lenalidomide; Chromosome 5q31.1 Deletion)Arm A (Lenalidomide; Randomization)Arm B (Lenalidomide + Epoetin Alfa; Randomization)Total
Female26332887
Male127078160
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Arm A (Lenalidomide; Chromosome 5q31.1 Deletion)Arm A (Lenalidomide; Randomization)Arm B (Lenalidomide + Epoetin Alfa; Randomization)Total
Hispanic or Latino2215
Not Hispanic or Latino349697227
Unknown or Not Reported25815
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Arm A (Lenalidomide; Chromosome 5q31.1 Deletion)Arm A (Lenalidomide; Randomization)Arm B (Lenalidomide + Epoetin Alfa; Randomization)Total
American Indian or Alaska Native0000
Asian1135
Native Hawaiian or Other Pacific Islander0000
Black or African American0134
White359796228
More than one race0000
Unknown or Not Reported24410
08

Study locations

507 sites
  • University of Alabama at Birmingham Cancer Center
    Birmingham, Alabama 35233, United States
  • Alaska Breast Care and Surgery LLC
    Anchorage, Alaska 99508, United States
  • Alaska Women's Cancer Care
    Anchorage, Alaska 99508, United States
  • Anchorage Oncology Centre
    Anchorage, Alaska 99508, United States
  • Katmai Oncology Group
    Anchorage, Alaska 99508, United States
  • Providence Alaska Medical Center
    Anchorage, Alaska 99508, United States
  • Fairbanks Memorial Hospital
    Fairbanks, Alaska 99701, United States
  • Mayo Clinic in Arizona
    Scottsdale, Arizona 85259, United States
  • Banner University Medical Center - Tucson
    Tucson, Arizona 85719, United States
  • University of Arizona Cancer Center-North Campus
    Tucson, Arizona 85719, United States
  • Kaiser Permanente-Anaheim
    Anaheim, California 92806, United States
  • Kaiser Permanente-Baldwin Park
    Baldwin Park, California 91706, United States
  • Kaiser Permanente-Bellflower
    Bellflower, California 90706, United States
  • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    Burbank, California 91505, United States
  • Kaiser Permanente-Fontana
    Fontana, California 92335, United States
  • Marin Cancer Care Inc
    Greenbrae, California 94904, United States
  • Kaiser Permanente South Bay
    Harbor City, California 90710, United States
  • Kaiser Permanente-Irvine
    Irvine, California 92618, United States
  • Kaiser Permanente Los Angeles Medical Center
    Los Angeles, California 90027, United States
  • Kaiser Permanente West Los Angeles
    Los Angeles, California 90034, United States
  • Fremont - Rideout Cancer Center
    Marysville, California 95901, United States
  • Stanford Cancer Institute Palo Alto
    Palo Alto, California 94304, United States
  • Kaiser Permanente - Panorama City
    Panorama City, California 91402, United States
  • Kaiser Permanente-Riverside
    Riverside, California 92505, United States
  • University of California Davis Comprehensive Cancer Center
    Sacramento, California 95817, United States
  • Kaiser Permanente-Rio San Diego
    San Diego, California 92108, United States
  • Kaiser Permanente-San Diego Zion
    San Diego, California 92120, United States
  • Kaiser Permanente-San Marcos
    San Marcos, California 92078, United States
  • Saint Helena Hospital
    St. Helena, California 94574, United States
  • Presbyterian Intercommunity Hospital
    Whittier, California 90602, United States
  • Kaiser Permanente-Woodland Hills
    Woodland Hills, California 91367, United States
  • The Medical Center of Aurora
    Aurora, Colorado 80012, United States
  • Boulder Community Foothills Hospital
    Boulder, Colorado 80303, United States
  • Penrose-Saint Francis Healthcare
    Colorado Springs, Colorado 80907, United States
  • Rocky Mountain Cancer Centers-Penrose
    Colorado Springs, Colorado 80907, United States
  • AdventHealth Porter
    Denver, Colorado 80210, United States
  • Colorado Blood Cancer Institute
    Denver, Colorado 80218, United States
  • Presbyterian - Saint Lukes Medical Center - Health One
    Denver, Colorado 80218, United States
  • Rocky Mountain Cancer Centers-Midtown
    Denver, Colorado 80218, United States
  • Saint Joseph Hospital - Cancer Centers of Colorado
    Denver, Colorado 80218, United States
  • Rocky Mountain Cancer Centers-Rose
    Denver, Colorado 80220, United States
  • Rose Medical Center
    Denver, Colorado 80220, United States
  • Western States Cancer Research NCORP
    Denver, Colorado 80222, United States
  • Mercy Medical Center
    Durango, Colorado 81301, United States
  • Mountain Blue Cancer Care Center - Swedish
    Englewood, Colorado 80113, United States
  • Swedish Medical Center
    Englewood, Colorado 80113, United States
  • Poudre Valley Hospital
    Fort Collins, Colorado 80524, United States
  • Mountain Blue Cancer Care Center
    Golden, Colorado 80401, United States
  • Saint Mary's Hospital and Regional Medical Center
    Grand Junction, Colorado 81501, United States
  • Banner North Colorado Medical Center
    Greeley, Colorado 80631, United States
  • Rocky Mountain Cancer Centers-Greenwood Village
    Greenwood Village, Colorado 80111, United States
  • CommonSpirit Saint Anthony Hospital Cancer Center
    Lakewood, Colorado 80228, United States
  • Rocky Mountain Cancer Centers-Lakewood
    Lakewood, Colorado 80228, United States
  • AdventHealth Littleton
    Littleton, Colorado 80122, United States
  • Rocky Mountain Cancer Centers-Sky Ridge
    Lone Tree, Colorado 80124, United States
  • Sky Ridge Medical Center
    Lone Tree, Colorado 80124, United States
  • Longmont United Hospital
    Longmont, Colorado 80501, United States
  • Banner North Colorado Medical Center - Loveland Campus
    Loveland, Colorado 80539, United States
  • AdventHealth Parker
    Parker, Colorado 80138, United States
  • Rocky Mountain Cancer Centers-Parker
    Parker, Colorado 80138, United States
  • Saint Mary Corwin Medical Center
    Pueblo, Colorado 81004, United States
  • North Suburban Medical Center
    Thornton, Colorado 80229, United States
  • Intermountain Health Lutheran Hospital
    Wheat Ridge, Colorado 80401, United States
  • University of Connecticut
    Farmington, Connecticut 06030, United States
  • Smilow Cancer Hospital Care Center at Saint Francis
    Hartford, Connecticut 06105, United States
  • The Hospital of Central Connecticut
    New Britain, Connecticut 06050, United States
  • Yale University
    New Haven, Connecticut 06520, United States
  • Beebe Medical Center
    Lewes, Delaware 19958, United States
  • Delaware Clinical and Laboratory Physicians PA
    Newark, Delaware 19713, United States
  • Helen F Graham Cancer Center
    Newark, Delaware 19713, United States
  • Medical Oncology Hematology Consultants PA
    Newark, Delaware 19713, United States
  • Christiana Care Health System-Christiana Hospital
    Newark, Delaware 19718, United States
  • Beebe Health Campus
    Rehoboth Beach, Delaware 19971, United States
  • TidalHealth Nanticoke / Allen Cancer Center
    Seaford, Delaware 19973, United States
  • Holy Cross Hospital
    Fort Lauderdale, Florida 33308, United States
  • Memorial Regional Hospital/Joe DiMaggio Children's Hospital
    Hollywood, Florida 33021, United States
  • Baptist MD Anderson Cancer Center
    Jacksonville, Florida 32207, United States
  • Mayo Clinic in Florida
    Jacksonville, Florida 32224-9980, United States
  • Jupiter Medical Center
    Jupiter, Florida 33458, United States
  • Leesburg Regional Medical Center
    Leesburg, Florida 34748, United States
  • University of Miami Miller School of Medicine-Sylvester Cancer Center
    Miami, Florida 33136, United States
  • Miami Cancer Institute
    Miami, Florida 33176, United States
  • Mount Sinai Medical Center
    Miami Beach, Florida 33140, United States
  • Moffitt Cancer Center
    Tampa, Florida 33612, United States
  • Augusta University Medical Center
    Augusta, Georgia 30912, United States
  • Saint Alphonsus Cancer Care Center-Boise
    Boise, Idaho 83706, United States
  • Saint Luke's Cancer Institute - Boise
    Boise, Idaho 83712, United States
  • Saint Luke's Cancer Institute - Fruitland
    Fruitland, Idaho 83619, United States
  • Saint Luke's Cancer Institute - Meridian
    Meridian, Idaho 83642, United States
  • Saint Luke's Cancer Institute - Nampa
    Nampa, Idaho 83687, United States
  • Kootenai Clinic Cancer Services - Post Falls
    Post Falls, Idaho 83854, United States
  • Saint Luke's Cancer Institute - Twin Falls
    Twin Falls, Idaho 83301, United States
  • Illinois CancerCare-Bloomington
    Bloomington, Illinois 61704, United States
  • Illinois CancerCare-Canton
    Canton, Illinois 61520, United States
  • Illinois CancerCare-Carthage
    Carthage, Illinois 62321, United States
  • Hematology and Oncology Associates
    Chicago, Illinois 60611, United States
  • Northwestern University
    Chicago, Illinois 60611, United States
  • Presence Resurrection Medical Center
    Chicago, Illinois 60631, United States
  • University of Chicago Comprehensive Cancer Center
    Chicago, Illinois 60637, United States
  • Weiss Memorial Hospital
    Chicago, Illinois 60640, United States

Showing the first 100 of 507 sites.

09

References and documents

Publications

  • List AF, Sun Z, Verma A, Bennett JM, Komrokji RS, McGraw K, Maciejewski J, Altman JK, Cheema PS, Claxton DF, Luger SM, Mattison RJ, Wassenaar TR, Artz AS, Schiffer CA, Litzow MR, Tallman MS. Lenalidomide-Epoetin Alfa Versus Lenalidomide Monotherapy in Myelodysplastic Syndromes Refractory to Recombinant Erythropoietin. J Clin Oncol. 2021 Mar 20;39(9):1001-1009. doi: 10.1200/JCO.20.01691. Epub 2021 Jan 13. PubMed 33439748 ↗

Study documents

  • Protocol and statistical analysis plan · Nov 7, 2019

Documents are hosted by the registry — open the source record to download them.

10

Updates

1 registry update since Sep 25, 2026
Sites
1 site added, 1 site removed
Show site
  • Vandalia Health/CAMC Institute for Academic Medicine · Charleston, United States
Show 1 removed
  • West Virginia University Charleston Division · Charleston, United States
Oct 1, 2026
Show all 1 update
  1. Oct 1, 2026
    1 site added, 1 site removed
    Show site
    • Vandalia Health/CAMC Institute for Academic Medicine · Charleston, United States
    Show 1 removed
    • West Virginia University Charleston Division · Charleston, United States

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

11

Registry details

Key details

Study ID
NCT00843882
Lead sponsor
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Feb 13, 2009
Start date
Apr 20, 2009
Primary completion
Jul 8, 2019
Completion
May 28, 2027 (estimated)
Results posted
Jul 8, 2021
Last update
Oct 1, 2026

Study contacts

Amit K Verma
principal investigator · ECOG-ACRIN Cancer Research Group

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is active, not recruiting, as verified in Jun 2026. You cannot join it, but the record below documents what was studied.

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