PHASE II STUDY OF LENALIDOMIDE AND ELTROMBOPAG IN PATIENTS WITH SYMPTOMATIC ANEMIA IN LOW OR INTERMEDIATE I MYELODYSPLASTIC SYNDROME (MDS)
1. Age ≥ 18 years.
2. Patient must have a documented diagnosis of MDS of at least three months duration
(MDS duration ≥ 3 months) according to World Health Organization (WHO) criteria (see
Appendix IV) or non-proliferative chronic myelomonocytic leukemia (CMML) (WBC ≤
3. Patients must have International Prognostic Scoring System (IPSS) categories of Low-
or Intermediate-1-risk disease (see Section 6).
4. Patients must have symptomatic anemia untransfused with hemoglobin ≤ 9.5 g/dL within
8 weeks of registration or with red blood cell (RBC) transfusion-dependence (i.e., ≥
2 units/month) confirmed for a minimum of 8 weeks before randomization.
5. Patients must have IPSS score determined by cytogenetic analysis prior to
randomization. Patients with cytogenetic failure and ≤ 10% marrow blasts will be
6. Patients must be off all disease modifying therapy for MDS for 28 days prior to
initiation of study treatment. Patients may receive hydrocortisone prophylactically
to prevent transfusion reactions.
7. 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 mg/100 mL or soluble transferring receptor <
8. Women must not be pregnant or breastfeeding. Females of childbearing potential should
have 2 negative pregnancy tests. The first test should be performed within 10-14
days, and the second test within 24 hours prior to prescribing lenalidomide.
9. 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
for at least 4 weeks before beginning lenalidomide therapy, 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 CC-5013 (lenalidomide) is
present in the semen of patients receiving the drug. Therefore, males receiving
CC-5013 (lenalidomide) must always use a latex condom during any sexual contact with
females of childbearing potential even if they have undergone a successful vasectomy.
10. Patients must not have received prior therapy with lenalidomide (for more than 2
months) nor eltrombopag.
11. Patients must not have uncontrolled hypertension.
12. Patients must have absolute neutrophil count (ANC) ≥500 cells/L (0.5 x 109/L).
13. ECOG Performance 0-3 (ECOG).
14. Prothrombin time (PT/INR) and activated partial thromboplastin time (aPTT) must be
within 80 to 120% of the normal range at baseline.
15. Patient is able to understand protocol requirements.
1. Pre-existing cardiovascular disease (including congestive heart failure, New York
Heart Association (NYHA) Grade III/IV), or arrhythmia known to increase the risk of
thromboembolic events (e.g. atrial fibrillation), or subjects with a corrected QT
interval (QTc) >450 msec.
2. Patients determined to be at increased risk of arterial or venous thrombosis by the
3. Bone marrow fibrosis that leads to a dry tap.
4. Female subjects who are nursing or pregnant (positive serum or urine -human chorionic
gonadotropin (-hCG) pregnancy test) at screening or pre-dose on Day 1.
5. Treatment with an investigational drug within 30 days or 5 half-lives (whichever is
longer) preceding the first dose of study medication.
6. Patients with documented liver cirrhosis
7. Patients with splenomegaly with a spleen size > 16cm.