Step 1: Randomization to Arm A or Arm B
Age > 18 years.
Patient must have documented diagnosis of MDS lasting at least three months
(MDS duration > 3 months) according to World Health Organization (WHO) criteria
(see Appendix IV) or non-proliferative chronic myelomonocytic leukemia (CMML)
(WBC < 12,000/mcL)).
Patient must have International Prognostic Scoring System (IPSS) categories of
Low- or Intermediate-1-risk disease (see Section 6). Patients must have IPSS score determined by cytogenetic analysis prior to randomization. Patients with cytogenetic failure and < 10% marrow blasts will be eligible.
Patients must have symptomatic anemia untransfused with hemoglobin < 9.5 g/dL
< 8 weeks prior to randomization or with 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 pretransfusion
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.
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 > 2g 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 pRBC/month, and serum
erythropoietin > 500mU/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. 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.
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
should have 2 negative pregnancy tests (sensitivity of at least 50 mIU/mL). The first test should be performed within 14 days prior to randomization, and the second test within 24 hours prior to prescribing lenalidomide.
Women of childbearing potential and sexually active males must agree to use 2
methods of an accepted and effective method of contraception and counseled on
the potential teratogenic effects of lenalidomide. Effective contraception must be used by patients during lenalidomide therapy, during dose interruptions and for 4 weeks following discontinuation of lenalidomide therapy. Reliable contraception is indicated even where there has been a history of infertility, unless due to hysterectomy or because the patient has been postmenopausal naturally for at least 24 consecutive months. Two reliable forms of contraception must be used simultaneously unless continuous abstinence from heterosexual sexual contact is the chosen method. Females of childbearing potential should be referred to a
qualified provider of contraceptive methods, if needed. Sexually mature females
who have not undergone a hysterectomy or who have not been postmenopausal
naturally for at least 24 consecutive months (i.e., who have had menses at some
time in the preceding 24 consecutive months) are considered to be females of
childbearing potential.
It is not known whether lenalidomide is present