Status and phase
Conditions
Treatments
Study type
Funder types
Identifiers
About
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
Full description
This pilot study will utilize an intra-patient dose escalation design. Cycles are 28 days in length. Subjects will receive lenalidomide 2.5 mg weekly during days 1 to 21 of cycle 1 (dose level 1). If patients do not experience any grade > 3 hematologic or non-hematologic toxicity, the dose will be increased to 2.5 mg twice weekly on days 1 to 21 of cycle 2 (dose level 2). If patients do not experience any grade > 3 hematologic or non-hematologic toxicity, the dose will be increased to 5 mg twice weekly on days 1 to 21 of cycle 3 (dose level 3). If patients do not experience any grade >3 hematologic or non-hematologic toxicity, the dose will be increased to 5 mg thrice weekly on days 1 to 21 of cycle 4 (dose level 4). Patients who experience grade >3 hematologic or non-hematologic toxicity at dose level 1 will be discontinued from study. Patients who experience grade > 3 hematologic or non-hematologic toxicity at dose level 2, 3, or 4 will have the lenalidomide held and dose reduced according to protocol dose interruption/modification algorithms (section 5.5.3). If at least a minor erythroid response is not achieved at the end of 8 cycles of treatment, patients will be discontinued from study. If a minor or major erythroid response is achieved after completion of 8 cycles of treatment, patients can continue study drug on a maintenance phase until loss of erythroid response (return to baseline hemoglobin or transfusion requirement) or unacceptable toxicity.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion 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:
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
Primary purpose
Allocation
Interventional model
Masking
2 participants in 1 patient group
Loading...
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal