Lenalidomide and Prednisone in Treating Patients With Myelofibrosis
Myelofibrosis with myeloid metaplasia (MMM) is a clonal hematopoietic stem cell disorder characterized by progressive anemia, marked splenomegaly, bone marrow collagen fibrosis, progression to acute leukemia, and premature death. MMM includes primary myelofibrosis and myelofibrosis from antecedent polycythemia vera or essential thrombocythemia. Anemia contributes to substantial symptoms of fatigue associated with myelofibrosis and is strongly correlated with shorter survival.
The pilot studies with thalidomide treatment both with and without prednisone tapers at the average dose of 200 mg/day have resulted in a clinically relevant improvement of anemia (20%), splenomegaly (23%), and thrombocytopenia (71%). However, a high incidence of adverse side effects including problematic neuropathy has motivated the investigation of a more potent thalidomide derivative with reduced toxicity.
Lenalidomide appears to have a similar range of activities as thalidomide with a better toxicity profile. In a large phase II trial with 68 subjects, lenalidomide administered at 10 mg/day resulted in overall response rates of 22% for anemia, 33% for splenomegaly, and 50% for thrombocytopenia. The promising results of the single agent activity of lenalidomide and the synergy between lenalidomide and corticosteroids has initiated the current phase II trial combining lenalidomide with a prednisone taper, which has been undertaken by the Eastern Cooperative Oncology Group (ECOG).
PURPOSE: This phase II trial is studying how well giving lenalidomide together with prednisone works in treating patients with myelofibrosis.
Chronic Myeloproliferative Disorders
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Lenalidomide (CC-5013) in Combination With Prednisone for the Treatment of Myelofibrosis With Myeloid Metaplasia|
- Overall Response Rate [ Time Frame: Assessed at the end of cycle 3 ] [ Designated as safety issue: No ]
Response was evaluated for Anemia and Spleen:
Major anemia response: hemoglobin increase to within normal limits in the absence of transfusion. Minor anemia response: hemoglobin improvement of at least 2 grams per deciliter independent of transfusion support, or achievement of transfusion independence in transfusion-dependent patients. Major spleen response: normalization of spleen size to the range of 12-14 centimeters by ultrasound. Minor spleen response: a 50% or more decrease in excess spleen size by ultrasound. Complete remission (CR): complete resolution of disease-related symptoms, splenomegaly, normalization of peripheral blood count, white cell differential and smear, and normalization of bone marrow histology. Partial remission (PR): a major or minor response in anemia or splenomegaly. Overall Response (OR)=CR + PR, assessed among eligible, treated patients.
|Study Start Date:||December 2005|
|Study Completion Date:||March 2012|
|Primary Completion Date:||December 2010 (Final data collection date for primary outcome measure)|
Lenalidomide 10 mg/day plus prednisone X 28 days X 3 cycles
10 mg/day plus prednisone X 28 days X 3 cycles
Other Name: CC-5013Drug: prednisone
For the first month, prednisone 30 mg/day was administered orally and was decreased to 15 mg/day for the second month, and then to 15 mg every other day for the third month.
- Determine the rate of complete or partial remission in patients with myelofibrosis with myeloid metaplasia treated with lenalidomide and prednisone.
- Determine the toxic effects of this regimen in these patients.
- Determine the duration of response in patients treated with this regimen.
- Determine the effect of this regimen on bone marrow fibrosis, angiogenesis, and cytogenetics in these patients.
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|Study Chair:||Ayalew Tefferi, MD||Mayo Clinic|
|Study Chair:||Larry D. Cripe, MD||Indiana University Melvin and Bren Simon Cancer Center|