Lenalidomide and Azacitidine in Treating Patients With Advanced Myelodysplastic Syndromes
- Conditions
- Myelodysplastic SyndromesLeukemia
- Interventions
- Registration Number
- NCT00352001
- Lead Sponsor
- Mikkael Sekeres MD
- Brief Summary
RATIONALE: Lenalidomide may stop the growth of cancer cells by blocking blood flow to the cancer. Lenalidomide may also stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Azacitidine may also cause cancer cells to look more like normal cells, and to grow and spread more slowly. Giving lenalidomide together with azacitidine may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of lenalidomide and azacitidine in treating patients with advanced myelodysplastic syndromes.
- Detailed Description
OBJECTIVES:
Primary
* Determine the maximum tolerated dose and dose-limiting toxicity of lenalidomide and azacitidine in patients with advanced myelodysplastic syndromes (MDS).
Secondary
* Review clinical outcomes, as defined by the International Working Group criteria, in patients treated with this regimen.
* Determine time to transformation to acute myeloid leukemia or death in patients treated with this regimen.
* Determine time to relapse after achieving complete or partial remission in patients treated with this regimen.
* Determine time to disease progression in patients treated with this regimen.
* Determine the effect of this regimen on hematologic status (including peripheral blood counts and the need for platelet and/or red blood cell transfusions) in these patients.
OUTLINE: This is an open-label, multicenter, dose-escalation study.
Patients receive oral lenalidomide once daily on days 1-14 or days 1-21 and azacitidine subcutaneously once daily on days 1-5 or days 1-5 and 8-12. Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses and/or increasing dosing frequencies of lenalidomide and azacitidine until the maximum tolerated dose (MTD) is determined or the sixth dose level is reached, whichever occurs first. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity during the first course of therapy.
After completion of study treatment, patients are followed annually.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 37
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Lenalidomide and Azacitidine azacitidine - Lenalidomide and Azacitidine lenalidomide -
- Primary Outcome Measures
Name Time Method PHASE I: Maximum Tolerated Dose of Azacitidine After 1 courses (1 months) Participants will be enrolled on the Phase I study portion in blocks of 3 to varying doses of Revlimid® (lenalidomide) and Vidaza® (azacitidine) (Table 1). To determine the MTD, a standard "3+3" design will be used. DLT will be assessed during the first cycle of therapy within each treatment group. No Maximum dose was reach but the go-forward dose agreed upon by the investigators is reported here.
PHASE II: Determine the Number of Patients With Responses for Efficacy(Measured as Response Rate) After 7 courses (months) For the Phase II study portion, to determine the efficacy (measured as response rate) of the combination therapy as defined by the International Working Group (IWG) criteria (CR, complete remission; PR, partial remission; or HI, hematological improvement)
Complete response (CR) is defined as: Disappearance of the chromosomal abnormality without appearance of new ones.
Partial response (PR) is defined as: At least 50% reduction of the chromosomal abnormality.
Hematologic Improvement (HI) is defined as: red blood cell increase of \>=1.5g/dL, a platelet response of \>=30X10\^9/L or by at least 100% for values starting \<20X10\^9/L, or a neutrophil response of at least 100% and absolute increase of \>0.5X10\^9/LPHASE I: Maximum Tolerated Dose of Lenalidomide After 1 courses (1 months) Participants will be enrolled on the Phase I study portion in blocks of 3 to varying doses of Revlimid® (lenalidomide) and Vidaza® (azacitidine) (Table 1). To determine the MTD, a standard "3+3" design will be used. DLT will be assessed during the first cycle of therapy within each treatment group. No Maximum dose was reach but the go-forward dose agreed upon by the investigators is reported here.
- Secondary Outcome Measures
Name Time Method Time to Transformation to Acute Myeloid Leukemia or Death After 7 months of treatment, until the date of first documented myeloid leukemia or death, whichever came first, assessed up to 55 months Time (in months) patients took to evolve to myeloid leukemia or death after achieving a complete response using the RECIST criteria
Time to Relapse After Achieving Complete Response After 7 months of treatment, until the date of first documented myeloid leukemia or death, whichever came first, assessed up to 55 months Number of Patients That Experience Grade 3 or 4 Treatment Related Non-hematologic Adverse Events After 7 months Overall Survival Among Patients With Complete Response After 7 months of treatment, until the date of first documented myeloid leukemia or death, whichever came first, assessed up to 55 months Time (in months) patients who achieved a complete response using the RECIST criteria were alive on study
Trial Locations
- Locations (3)
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
🇺🇸Tampa, Florida, United States
University of California at Los Angeles
🇺🇸Los Angeles, California, United States
Cleveland Clinic Taussig Cancer Instititute, Case Comprehensive Cancer Center
🇺🇸Cleveland, Ohio, United States