A phase I/II clinical trial of fludarabine, bendamustine, and rituximab (FBR) in previously treated patients with chronic lymphocytic leukemia (CLL)
William G. Wierda
The goal of Phase 1 of this clinical research study is to find the highest tolerable dose of bendamustine, combined with fludarabine and rituximab, that can be given to patients who have CLL that has been treated before. The goal of Phase 2 of this study is to find out if this drug combination can help to control the disease. The safety of this drug combination will also be studied.
Disease Group: Leukemia
Treatment Agent: Bendamustine HCl,Fludarabine,Rituximab
Treatment Location: Only at MDACC
Estimatated Length of Stay in Houston: None
Return Visit: After the 3rd and 6th courses (or the last course if fewer than 6 given) for response assessment.
Home Care: Treatment may be given at home for C 2-6.
Primary objectives: · Phase I – Evaluate the toxicities and tolerability and identify the maximum tolerated dose (MTD) of bendamustine combined with fixed-dose fludarabine and rituximab (FBR) in previously treated patients with Chronic Lymphocytic Leukemia (CLL). · Phase II – Evaluate efficacy (2008 International Workshop on Chronic Lymphocytic Leukemia [IWCLL] response rate) of the FBR regimen at the tolerated dose of bendamustine in previously treated patients with CLL. This will be compared to the historic data of treatment regimens for previously treated patients with CLL. Secondary objectives: · Evaluate safety in the Phase II portion at the tolerated dose of bendamustine in previously treated patients with CLL. · Evaluate time to treatment failure (TTF) and time-to-progression (TTP) for previously treated patients treated with the FBR combination. These time-to-event endpoints will be compared to historic data of treatment regimens for previously treated patients. · Correlate pretreatment prognostic factors, including ZAP-70 expression, CD38 expression, beta 2 microglobulin, IGHV gene mutation status, chromosome abnormalities by FISH, and serum thymidine kinase with response and time to event endpoints. · Evaluate pharmacodynamic endpoints to determine bendamustine-induced deoxyribonucleic acid (DNA) damage response in quiescent CLL lymphocytes and test the hypothesis that fludarabine triphosphate will enhance this response by inhibiting DNA repair.
IRB Review and Approval Date: 04/19/2010
Recruitment Status: Not Accepting
Projected Accrual: N/A
1) Patients must have a diagnosis of CLL/Small Lymphocytic Lymphoma
(SLL) and be previously treated
2) Patients must have an indication for treatment by 2008 IWCLL Criteria
3) Age >/= 16 years
4) Zubrod performance status </= 2
5) Adequate renal and hepatic function as indicated by all the following: a. serum creatinine </= 2 mg/dL AND; b. alanine aminotransferase (ALT) </= 2.5 times upper limit of normal AND; c. total bilirubin </= 2.5 times upper limit of normal
6) Patients must give written informed consent
7) Patients of childbearing potential must be willing to practice birth control during the study
1) Pregnant or breast-feeding females
2) Significant co-morbidity indicated by major organ system dysfunction
3) Active, uncontrolled infection, including active hepatitis
4) Uncontrolled autoimmune hemolytic anemia (AIHA) or immune thrombocytopenia purpura (ITP)
5) Treatment including chemotherapy, chemoimmunotherapy, monoclonal antibody therapy, radiotherapy, high-dose corticosteroid therapy (Prednisone >/ 60 mg daily or equivalent), or immunotherapy within 21 days prior to enrollment or concurrent with this trial
Information and next steps
Phase I/Phase II
William G. Wierda
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