A 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 Myelodysplastic Syndrome (MDS) and Symptomatic Anemia


Myeloid and Monocytic Leukemia

Trial Phase

Phase III

Trial Purpose and Description

Trial Purpose

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 cell. 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.

Participation Guidelines


Eligibility Criteria

Inclusion Criteria:

  • Documented diagnosis of 1 of the following:

    • Myelodysplastic syndromes (MDS) lasting at least 3 months (MDS duration >= 3 months) according to World Health Organization (WHO) criteria or non-proliferative chronic myelomonocytic leukemia (CMML) (white blood cells [WBC] < 12,000/mcL)
  • International prognostic scoring system (IPSS) category of low- or intermediate-1-risk MDS as determined by cytogenetic analysis

    • Cytogenetic analysis required if current bone marrow biopsy is a dry tap
    • Patients with cytogenetic failure and < 10% marrow blasts are eligible

      • Patients with cytogenetic failure must have prior 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
  • For patients without the deletion 5q 31.1, must have failed treatment with an erythropoietic growth factor OR have a low probability of response to rhu-erythropoietin, as defined by the following:

    • Prior erythropoietin failure: requires >= 40,000 units epoetin alfa/week for 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 >= 2 g rise in hemoglobin sustained for >= 4 weeks in non-transfusion dependent patients
    • Low erythropoietin response profile: rhu-erythropoietin and epoetin alfa-naive patients receiving >= 2 U pRBC/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
  • No documented iron deficiency

    • Must have documented bone marrow iron stores (if marrow iron stain is not available, transferrin saturation must be > 20% or serum ferritin > 100 ng/mL)
  • Women must not 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 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 seizures 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 (without platelet transfusion)
  • Absolute neutrophil count (ANC) >= 500 cells/mcL (must be >= 500/mcL without myeloid growth factor support)
  • Serum creatinine =< 1.5 times upper limit of normal (ULN)
  • Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) or serum glutamic pyruvate transaminase (SGPT)/alanine aminotransferase (ALT) =< 2.0 x ULN
  • Serum total bilirubin < 3.0 mg/dL
  • Prior thalidomide 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

Eastern Cooperative Oncology Group
Last Updated:
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