Pilot Lenalidomide in Adult Diamond-Blackfan Anemia Patients w/ RBC Transfusion-Dependent Anemia
Condition: Anemia; Leukemia; Acute Myeloid Leukemia (AML); Myelodysplastic Syndromes (MDS)
MeSH terms: Leukemia; Leukemia, Myeloid, Acute; Preleukemia; Anemia; Myelodysplastic Syndromes; Anemia, Diamond-Blackfan
Intervention: Lenalidomide
Intervention description: 2.5 mg/wk up to 5 mg 3x/wk
Intervention MeSH terms: Lenalidomide
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a single-center, single arm, open-label study of oral lenalidomide monotherapy
      administered to red blood cell (RBC) transfusion dependent adult subjects with
      Diamond-Blackfan Anemia (DBA).

      Primary Objective: To evaluate the erythroid response rate as measured by rate of red blood
      cell transfusion independence [MDS International Working Group (IWG) 2000 Criteria will be
      applied].

      Secondary Objective: 1)To evaluate the tolerability and safety profile of lenalidomide in
      patients with DBA and other inherited marrow failure syndromes 2) To correlate response to
      lenalidomide with biologic surrogates of DBA including ribosomal protein mutation status, ex
      vivo erythroid colony growth, and microarray gene expression
    

Eligibility criteria:

        INCLUSION CRITERIA

          -  Understand and voluntarily sign an informed consent form

          -  Diagnosis of DBA

          -  Age ≥ 18 years at the time of signing the informed consent form.

          -  Able to adhere to the study visit schedule and other protocol requirements.

          -  Red blood cell transfusion-dependent with a requirement of at least one unit of RBCs
             per month for the 2 months prior to study enrollment (eg, 2 units/8 weeks)

          -  If applicable, ongoing therapy with a stable or decreasing dose of prednisone ≤ 60
             mg/d or corticosteroid equivalent, for which there has been no treatment-related
             improvement in RBC transfusion requirements for at least 2 months prior to study entry

          -  Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 at study entry.

          -  Laboratory test results within these ranges:

               -  Absolute neutrophil count (ANC) ≥ 1500/uL

               -  Platelet (Plt) count ≥ 100,000/uL

               -  Serum creatinine ≤ 2.0 mg/dL

               -  Direct bilirubin ≤ 1.5 mg/dL

               -  Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN)

               -  Alanine aminotransferase (ALT) ≤ 2.5 x ULN

               -  Disease-free of prior malignancies for ≥ 5 years with exception of currently
                  treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in-situ"
                  of the cervix or breast

          -  Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
             test with a sensitivity of ≥ 50 milli-International Units (MIU)/mL within 10 to 14
             days prior to and again within 24 hours of prescribing lenalidomide (prescriptions
             must be filled within 7 days) and must either commit to continued abstinence from
             heterosexual intercourse or begin 2 acceptable methods of birth control, one highly
             effective method and one additional effective method at the same time, at least 28
             days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy
             testing. Men must agree to use a latex condom during sexual contact with a FCBP even
             if they have had a successful vasectomy

          -  Able to take aspirin (81 to 325 mg) daily as prophylactic anticoagulation (patients
             intolerant to aspirin may use warfarin or low molecular weight heparin)

        EXCLUSION CRITERIA

          -  Any serious medical condition, laboratory abnormality, or psychiatric illness that
             would prevent the subject from signing the informed consent form.

          -  Pregnant or breast feeding females. (Lactating females must agree not to breast feed
             while taking lenalidomide)

          -  Any condition, including the presence of laboratory abnormalities, which places the
             subject at unacceptable risk if he/she were to participate in the study or confounds
             the ability to interpret data from the study

          -  Use of any other experimental drug or therapy (excluding steroids) specifically used
             for DBA within 28 days of baseline including metoclopramide, leucine, danazol, or
             other hormonal therapy

          -  Clinically significant anemia due to factors such as iron, B12, folate deficiencies,
             autoimmune or hereditary hemolysis, or gastrointestinal bleeding.

          -  Known hypersensitivity to thalidomide

          -  The development of erythema nodosum if characterized by a desquamating rash while
             taking thalidomide or similar drugs

          -  Any prior use of lenalidomide

          -  Concurrent use of other anti-cancer agents or treatments

          -  Known positive for HIV or infectious hepatitis, type A, B or C