Phase II Study of Lenalidomide and Eltrombopag in Patients With Symptomatic Anemia
Condition: Adult Myelodysplastic Syndrome; Anemia; Chronic Myelomonocytic Leukemia
MeSH terms: Preleukemia; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Anemia; Myelodysplastic Syndromes; Syndrome
Intervention: Eltrombopag Olamine; Laboratory Biomarker Analysis; Lenalidomide
Intervention description: Given PO; Correlative studies; Given PO
Intervention MeSH terms: Lenalidomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 52.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well lenalidomide (LEN) and eltrombopag olamine (ELT) work in
      treating patients with symptomatic anemia in low or intermediate myelodysplastic syndrome
      (MDS). Lenalidomide may stimulate the immune system in different ways and stop cancer cells
      from growing. Eltrombopag olamine may increase the number of white blood cells and platelets
      found in bone marrow or peripheral blood. Giving lenalidomide and eltrombopag olamine may be
      an effective treatment for myelodysplastic syndrome.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patient must have a documented diagnosis of myelodysplastic syndrome (MDS) of at least
             three months duration (MDS duration >= 3 months) according to World Health
             Organization (WHO) criteria or non-proliferative chronic myelomonocytic leukemia
             (CMML) (white blood cells [WBC] =< 12,000/L)

          -  Patients must have International Prognostic Scoring System (IPSS) categories of low-
             or intermediate-1-risk disease

          -  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

          -  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 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

          -  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/100 mL or soluble transferring receptor <
             5 mg/L.

          -  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 10-14 days, and the second test within 24 hours prior to
             prescribing lenalidomide

          -  Females of reproductive potential must adhere to the scheduled pregnancy testing as
             required in the Revlimid REMS® program; able to take aspirin (81 or 325 mg) daily as
             prophylactic anticoagulation (patients intolerant to acetylsalicylic acid [ASA] may
             use warfarin or low molecular weight heparin)

          -  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

          -  Patients must not have received prior therapy with lenalidomide (for more than 2
             months) nor eltrombopag

          -  Patients must not have uncontrolled hypertension

          -  Patients must have absolute neutrophil count (ANC) >= 500 cells/L (0.5 x 10^9/L)

          -  Eastern Cooperative Oncology Group (ECOG) performance 0-3

          -  Subject is able to understand and comply with protocol requirements and instructions

          -  Patient has signed and dated informed consent

          -  Prothrombin time (PT/international normalized ratio [INR]) and activated partial
             thromboplastin time (aPTT) must be within 80 to 120% of the normal range at baseline

        Exclusion Criteria:

          -  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

          -  Patients determined to be at increased risk of arterial or venous thrombosis by the
             investigator

          -  Bone marrow fibrosis that leads to a dry tap

          -  Female subjects who are nursing or pregnant (positive serum or urine beta-human
             chorionic gonadotropin (beta-hCG) pregnancy test) at screening or pre-dose on day 1

          -  Treatment with an investigational drug within 30 days or 5 half-lives (whichever is
             longer) preceding the first dose of study medication

          -  Patients with documented liver cirrhosis

          -  Patients with splenomegaly with a spleen size > 16 cm