Alternating Thalidomide and Lenalidomide Therapy Plus Rituximab (ThRiL) as Initial Treatment for Patients With CLL
- Conditions
- Chronic Lymphocytic Leukemia
- Interventions
- Registration Number
- NCT01125176
- Lead Sponsor
- Weill Medical College of Cornell University
- Brief Summary
The investigators' hypothesis is that treatment of CLL with an alternating daily dosing schedule of thalidomide and lenalidomide may result in better tolerability by decreasing each agent's individual toxicities, while preserving efficacy, and therefore lead to a longer duration of therapy and improved responses. Additionally, the combination of the 2 agents may have additive or synergistic effects therapeutically.
In Cycle -1, odd numbered patients will receive oral thalidomide daily days 1-14 followed by no treatment on days 15-28. Even numbered patients will receive oral lenalidomide daily on days 1-14 and then no treatment on days 15-28. Starting with cycle 1, patients will alternate daily thalidomide (every odd day) with daily lenalidomide (every even day) for days 1-28. Rituximab will be given on days 1, 8, 15, and 22 starting with Cycle 1, and then again every 6th cycle thereafter (cycles 7, 13, 19, etc.)
- Detailed Description
This is an open label, phase II, single arm, and single institution study investigating daily alternating therapy with IMiDâ„¢ compounds, thalidomide and lenalidomide, plus rituximab in untreated CLL patients requiring treatment. In order to obtain correlative samples, patients will receive a two week course of single agent thalidomide or lenalidomide before beginning treatment with the combination regimen. Half of the patients (odd numbered subjects) will start with a two week course of single agent thalidomide and the other half of the patients (even numbered subjects) will start with a two week course of single agent lenalidomide. This will allow the study of correlative samples of monotherapy with either IMiDâ„¢ agent. In Cycle -1 half of the patients (odd numbered subjects) will receive thalidomide 50mg PO daily on days 1-14, followed by no treatment days 15-28 and the other half of the patients (even numbered subjects) will receive lenalidomide PO daily on days 1-14, followed by no treatment days 15-28. Starting cycle 1: Patients will receive thalidomide 50 mg every other day (every odd day on days 1-28: Days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 \& 27 of a 28 day cycle) alternating with lenalidomide on alternate every other day, dosed based upon current level with stepwise incremental dosing (every even day on days 1-28: Days 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26 \& 28 of a 28 day cycle). The starting dose of lenalidomide will be based on calculated creatinine clearance and the dose of lenalidomide may be escalated as tolerated to maximal dose of 25 mg (see Section 5 for details). Rituximab 375 mg/m2 will be administered on days 1, 8, 15 and 22 starting with Cycle 1 and then again on the same weekly x 4 schedule every 6th cycle thereafter (Cycles 7, 13, 19, etc).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 15
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description All subjects rituximab In Cycle -1, even numbered patients will receive oral lenalidomide daily on days 1-14 and then no treatment on days 15-28. In Cycle -1, odd numbered patients will receive oral thalidomide daily days 1-14 followed by no treatment on days 15-28. Starting with cycle 1, all patients will alternate daily thalidomide (every odd day) with daily lenalidomide (every even day) for days 1-28. Rituximab will be given on days 1, 8, 15, and 22 starting with Cycle 1, and then again every 6th cycle thereafter (cycles 7, 13, 19, etc.) All subjects thalidomide In Cycle -1, even numbered patients will receive oral lenalidomide daily on days 1-14 and then no treatment on days 15-28. In Cycle -1, odd numbered patients will receive oral thalidomide daily days 1-14 followed by no treatment on days 15-28. Starting with cycle 1, all patients will alternate daily thalidomide (every odd day) with daily lenalidomide (every even day) for days 1-28. Rituximab will be given on days 1, 8, 15, and 22 starting with Cycle 1, and then again every 6th cycle thereafter (cycles 7, 13, 19, etc.) All subjects lenalidomide In Cycle -1, even numbered patients will receive oral lenalidomide daily on days 1-14 and then no treatment on days 15-28. In Cycle -1, odd numbered patients will receive oral thalidomide daily days 1-14 followed by no treatment on days 15-28. Starting with cycle 1, all patients will alternate daily thalidomide (every odd day) with daily lenalidomide (every even day) for days 1-28. Rituximab will be given on days 1, 8, 15, and 22 starting with Cycle 1, and then again every 6th cycle thereafter (cycles 7, 13, 19, etc.)
- Primary Outcome Measures
Name Time Method Overall Response Rate as Defined as the Number of Patients Who Experience a Response (Complete or Partial) to Treatment at the Time of Best Response From date of study drug initiation until date of best response, assessed up to 6 years. Response will be evaluated in this study using the International Workshop on CLL (IWCLL) update of the 1996 NCI-Working Group criteria for CLL, which includes assessment of the following: clonal lymphocytes in the peripheral blood by flow cytometry, blood tests for neutrophil count, hemoglobin, and platelet count, CT examination for lymphadenopathy, hepatomegaly, splenomegaly, constitutional symptoms, bone marrow assessment via biopsy/aspirate, and evaluation for disease transformation.
- Secondary Outcome Measures
Name Time Method Time to Response From date of study drug initiation to date of initial response, assessed up to 12 months. Measured from time of study drug administration to initial response (partial or complete), measured in months.
Overall Survival From date of study drug initiation to date of death, assessed through study completion up to 105 months. Measured from time of study drug administration to death, measured in months.
Progression Free Survival From date of study drug initiation until date of progression or death, whichever occurs first, assessed through study completion up to 100 months. Measured from time of study drug administration to progression or death, measured in months.
Duration of Response From date of end of treatment to progression or death, whichever occurs first, assessed through study completion up to 100 months. Measured from end of treatment to progression or death, measured in months.
Trial Locations
- Locations (1)
Weill Cornell Medical College
đŸ‡ºđŸ‡¸New York, New York, United States