A Time-Limited Approach to Treatment with Ibrutinib for Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
- >= 18-years-old
- Diagnosis of CLL or small lymphocytic lymphoma (SLL) confirmed by the enrolling institution
- Negative del(17p) test confirmed by fluorescence in situ hybridization (FISH) testing prior to initiating treatment with ibrutinib
- Receiving commercial treatment with an ibrutinib-based regimen in the front-line setting as defined below with the intent to discontinue therapy on C1D1: * Ibrutinib monotherapy * Ibrutinib in combination with anti-CD20 monoclonal antibody (Patients must have completed the anti-CD20 monoclonal antibody portion of the regimen prior to signing consent)
- Patients must have received ibrutinib-based therapy for at least 15 months. Dose interruptions and reductions during this treatment period may have been carried out per treating provider discretion
- Response evaluation performed by radiology assessment (computed tomography [CT] or magnetic resonance imaging [MRI] imaging of neck/chest/abdomen/pelvis) confirming complete remission or partial remission by iwCLL criteria
- Peripheral blood (by flow cytometry per institutional standards) testing for MRD confirming U-MRD to a sensitivity of 10-4. MRD testing must be confirmed to follow ERIC consensus criteria * Complete response (CR) with or without U-MRD in peripheral blood * Partial response (PR) with U-MRD in peripheral blood
- Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator’s opinion, could compromise the subject’s safety or put the study outcomes at undue risk
- Unwilling or unable to participate in all required study evaluations and procedures. Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local patient privacy regulations)
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.
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.
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.
Trial Phase Phase II
Trial Type Treatment
Memorial Sloan Kettering Cancer Center
Anthony R. Mato
- Primary ID 20-284
- Secondary IDs NCI-2021-00042
- Clinicaltrials.gov ID NCT04694560