Ibrutinib and PD-1 Blockade in High Risk Lymphocytic Leukemia

Phase II Trial of Ibrutinib and PD-1 Blockade in High Risk Chronic Lymphocytic Leukemia to Improve Immune Dysfunction

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.

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