Clinical Trial: Pilot Lenalidomide in Adult Diamond-Blackfan Anemia Patients w/ RBC Transfusion-Dependent Anemia

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Pilot Study of Lenalidomide in Adult Diamond-Blackfan Anemia Patients With Red Blood Cell Transfusion-Dependent Anemia

Brief 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


Detailed Summary: 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.
Sponsor: Jason Robert Gotlib

Current Primary Outcome: Red Blood Cell (RBC) Transfusion Independence [ Time Frame: 6 months ]

Red blood cell (RBC) transfusion independence is reported as the number of subjects who achieve a continuous absence of the intravenous infusion of any RBC transfusion during any consecutive "rolling" 56 days during the treatment period.


Original Primary Outcome: RBC Transfusion Independence [ Time Frame: Assessment done every 56 days: D56, D112, D168, D224, then every month during Maintenance Phase ]

Current Secondary Outcome:

  • Red Blood Cell (RBC) Transfusions [ Time Frame: 6 months ]
    The effect on red blood cell (RBC) transfusions was assessed as the number of participants that achieved a greater than 50% decrease in RBC transfusion requirements.
  • Hemoglobin Concentration [ Time Frame: 6 months ]
    The effect on hemoglobin concentration was assessed as the change from baseline, measured in g/dL.
  • Neutrophil Response [ Time Frame: 6 months ]
    The effect on neutrophil levels was assessed as the change in neutrophil count from baseline.
  • Platelet Response [ Time Frame: 6 months ]
    The effect on platelet levels as assessed as the change in platelet count from baseline.
  • Duration of Response [ Time Frame: 6 months ]
    The response duration was measured from the last of the consecutive 56 days during which the subject was free of red blood cells (RBC) transfusions to the date of the first RBC transfusion after the 56-day RBC-transfusion-free period.
  • Toxicity [ Time Frame: 6 months ]
    Toxicity was assessed as the number of adverse events related to lenalidomide.


Original Secondary Outcome:

  • >50% Decrease in RBC Transfusion Requirements [ Time Frame: Assessment done every 56 days: D56, D112, D168, D224, then every month during Maintenance Phase ]
  • Change of Hemoglobin Concentration From Baseline [ Time Frame: Assessed weekly up to end of cycle 8 (Day 224) or Early Discontinuation, then every two weeks during Maintenance Phase with an additional assessment done 30 days (+/- 3 days) after last dose of study drug ]
  • Neutrophil Response [ Time Frame: Assessed weekly up to end of cycle 8 (Day 224) or Early Discontinuation, then every two weeks during Maintenance Phase with an additional assessment done 30 days (+/- 3 days) after last dose of study drug ]
  • Platelet Response [ Time Frame: Assessed weekly up to end of cycle 8 (Day 224) or Early Discontinuation, then every two weeks during Maintenance Phase with an additional assessment done 30 days (+/- 3 days) after last dose of study drug ]
  • Bone Marrow Response [ Time Frame: End of cycle 8 (Day 224) or Early Discontinuation, then every 6 months during Maintenance Phase ]
  • Duration of Response [ Time Frame: Day 56 and end of cycle 8 (Day 224) or Early Discontinuation, then every month during Maintenance Phase ]
  • Safety (Type, Frequency, Severity, and Relationship of Adverse Events to Lenalidomide) [ Time Frame: Safety is monitored on a continuous basis throughout the trial period, and for 30 days after last dose of study medication ]
  • Correction of Clinical Response With Ribosomal Protein Mutation Status and ex Vivo Effects of Lenalidomide on Marrow Erythroid Colony Growth and Microarray Gene Expression Signatures [ Time Frame: Assessment done end of cycle 8 (Day 224) ]


Information By: Stanford University

Dates:
Date Received: December 15, 2009
Date Started: November 2009
Date Completion:
Last Updated: March 22, 2017
Last Verified: March 2017