A Time-Limited Approach to Treatment with Ibrutinib for Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

PRIMARY OBJECTIVE:

I. To estimate treatment free survival (TFS) at 12 cycles for patients who discontinue front-line ibrutinib while in either a) complete remission (CR) with or without undetectable minimal residual disease (U-MRD), or 2) partial remission (PR) with U-MRD of peripheral blood after at least 15 months of ibrutinib-based therapy.

SECONDARY OBJECTIVES:

I. To estimate progression free survival (PFS) and overall survival (OS) at 12 and 24 cycles after discontinuation of ibrutinib-based therapy.

II. To estimate treatment free survival at 24 cycles after discontinuation of ibrutinib-based therapy.

III. To estimate the relationship between minimal residual disease (MRD) in peripheral blood of patients who achieve CR at the time of ibrutinib discontinuation and PFS, OS.

IV. To evaluate presence of BTK and PLCG2 mutations after >= 15 months of ibrutinib-based therapy and, for those experiencing clinical relapse requiring reintroduction of therapy, at the time of retreatment after a period of drug discontinuation.

V. To examine resolution of adverse events following discontinuation of ibrutinib.

VI. To estimate overall response rate (ORR) following reintroducing ibrutinib-based therapy (in aggregate and stratified by regimen received) for progression of chronic lymphocytic leukemia (CLL) requiring treatment per international workshop on CLL (iwCLL)1 guidelines.

VII. To assess toxicity profile of ibrutinib-based therapy in retreatment when used for clinical relapse of CLL requiring treatment per iwCLL guidelines.

VIII. To examine health-related quality of life (via Functional Assessment of Cancer Therapy [FACT]-Leukemia, and Functional Assessment of Chronic Illness Therapy [FACIT]-fatigue) prior to and at serial time points following ibrutinib discontinuation and following retreatment.

OUTLINE:

Patients discontinue treatment with ibrutinib. Patients then undergo observation on day 1 of cycles 1-3 and then every 3 cycles through cycle 24. Patients whose cancer comes back or gets worse may restart treatment with ibrutinib or another treatment and undergo observation for an additional 12 cycles following start of reintroduction of therapy.