Triple Drug Therapy for Chronic Lymphocytic Leukemia
Trial Summary
What is the purpose of this trial?
Background: Chronic lymphocytic leukemia and small lymphocytic lymphoma (hereby referred as CLL) are tumors of B cells. A subset of patients categorized as high-risk CLL has a poor clinical outcome when treated with conventional chemotherapy. This single-arm, phase II study investigates the combination of ibrutinib, fludarabine and pembrolizumab for treatment of CLL. Ibrutinib is an orally administered therapy for CLL. Fludarabine is a well-tolerated drug that has been widely used to treat CLL. Also, fludarabine can modulate CLL cells as well as immune cells that support the growth of CLL cells. Pembrolizumab recruits immune cells to attack CLL cells. With this approach we hope to achieve a greater reduction in CLL cells than with single agent ibrutinib and to restore healthier immune system that could contribute to durable responses. Objective: To investigate the rate of complete response to ibrutinib, short course fludarabine and pembrolizumab. Eligibility: Patients with active CLL meeting treatment indications defined by 2008 International Workshop on CLL (IWCLL) consensus guideline. High-risk CLL defined by one of the following: * Relapsed/refractory disease status, or * Presence of high-risk mutations regardless of prior treatment status: deletion 17p, TP53 mutation, NOTCH1 mutation, SF3B1 mutation, MYC aberration, or complex cytogenetics. Design: This is a single-arm, open-label phase II study. Timeline: Treatment on this study is given in cycles from cycle -3 to 17, then in months beyond cycle 17. Cycles -3 to -1 are 28-day cycles. Cycles 1 to 17 are 21-day cycles. After completion of 1 year of pembrolizumab, the time on study is by chronological months on study from starting pembrolizumab. Treatment plan: * Ibrutinib is given starting from cycle -3 and continuously until disease progression or intolerable side effects occur. * Fludarabine is given on D1-D5 on cycle -2 only * Pembrolizumab is given every 3 weeks starting from cycle 1 for 1 year. * Minimal residual disease will be measured at 2 years from cycle 1 to determine the need for long- term treatment with ibrutinib. * Previously-untreated patients who achieve minimal residual disease negativity will stop ibrutinib. * Patients who do not achieve minimal residual disease negativity or who has Relapsed/refractory CLL will continue ibrutinib.
Research Team
Adrian U Wiestner, M.D.
Principal Investigator
National Heart, Lung, and Blood Institute (NHLBI)
Eligibility Criteria
This trial is for adults with active, high-risk or relapsed/refractory Chronic Lymphocytic Leukemia (CLL) who meet specific criteria including weight loss, presence of certain mutations, progressive symptoms, and adequate organ function. Participants must not have a history of certain infections or conditions that could affect the study's safety or outcomes.Inclusion Criteria
Exclusion Criteria
Treatment Details
Interventions
- Fludarabine (Anti-metabolites)
- Ibrutinib (Kinase Inhibitor)
- Pembrolizumab (Monoclonal Antibodies)
Fludarabine is already approved in Canada for the following indications:
- Chronic lymphocytic leukemia
- Non-Hodgkin's lymphoma
Find a Clinic Near You
Who Is Running the Clinical Trial?
National Heart, Lung, and Blood Institute (NHLBI)
Lead Sponsor