Phase II Trial of Ibrutinib and PD-1 Blockade in High Risk Chronic Lymphocytic Leukemia to Improve Immune Dysfunction
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab
- Conditions
- Chronic Lymphocytic Leukemia
- Sponsor
- H. Lee Moffitt Cancer Center and Research Institute
- Enrollment
- 5
- Locations
- 1
- Primary Endpoint
- Overall Response Rate (ORR) to the Therapeutic Intervention
- Status
- Terminated
- Last Updated
- 4 months ago
Overview
Brief Summary
The purpose of this study is to evaluate the impact of sequential overlapping treatment with PD-1 monoclonal antibody (mAb), pembrolizumab/MK-1375, followed by ibrutinib on endogenous immune function in previously untreated, high-risk CLL patients. Immune function will be evaluated through various laboratory correlative tests.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Have high risk CLL
- •Have documented previously untreated CLL according to IWCLL criteria
- •Willing and able to provide written informed consent
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Demonstrate adequate organ function
- •Able to take oral medication and willing to adhere to the medication regimen
Exclusion Criteria
- •Currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment
- •Meets IWCLL criteria to start therapy
- •Has had any treatment for CLL including any investigational agent, chemotherapy, mAb, anti-PD-1, anti-PDL-1, or anti-CTLA-4
- •Transformation of CLL to aggressive NHL (Richter's transformation or pro-lymphocytic leukemia)
- •Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 90 days after the last dose of trial treatment
- •Major surgery or a wound that has not fully healed within 4 weeks of first dose
- •Additional criteria may apply
Arms & Interventions
Pembrolizumab and Ibrutinib
Treatment with pembrolizumab and ibrutinib and follow-up period of up to 24 months. Pembrolizumab is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Ibrutinib is an inhibitor of Bruton's tyrosine kinase (BTK). Ibrutinib is a small-molecule inhibitor of BTK.
Intervention: Pembrolizumab
Pembrolizumab and Ibrutinib
Treatment with pembrolizumab and ibrutinib and follow-up period of up to 24 months. Pembrolizumab is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Ibrutinib is an inhibitor of Bruton's tyrosine kinase (BTK). Ibrutinib is a small-molecule inhibitor of BTK.
Intervention: Ibrutinib
Outcomes
Primary Outcomes
Overall Response Rate (ORR) to the Therapeutic Intervention
Time Frame: Up to 2 years
Response categories according to The International Workshop on Chronic Lymphocytic Leukemia (IWCLL): Complete remission (CR); Complete remission with incomplete marrow recovery (CRi); Partial remission (PR); Progressive disease (PD); Stable disease (SD), defined as not meeting criteria for CR, CRi, PR or PD.
Time to Best Response
Time Frame: Up to 2 years
Time to best response to chronic lymphocytic leukemia (CLL) to the therapeutic intervention.
Secondary Outcomes
- Progression-free Survival (PFS)(Up to 2 years)