Description:
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.
Title
- Brief Title: Ibrutinib and PD-1 Blockade in High Risk Lymphocytic Leukemia
- Official Title: Phase II Trial of Ibrutinib and PD-1 Blockade in High Risk Chronic Lymphocytic Leukemia to Improve Immune Dysfunction
Clinical Trial IDs
- ORG STUDY ID:
MCC-19199
- NCT ID:
NCT03514017
Conditions
- Chronic Lymphocytic Leukemia
Interventions
Drug | Synonyms | Arms |
---|
Pembrolizumab | Keytruda® | Pembrolizumab and Ibrutinib |
Ibrutinib | Imbruvica® | Pembrolizumab and Ibrutinib |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Pembrolizumab and Ibrutinib | Experimental | 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. | |
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Overall Response Rate (ORR) to the Therapeutic Intervention |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | 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. |
Secondary Outcome Measures
Measure: | Restoration of Immune Response |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | Restoration of immune response as measured by: Decreased markers of T-cell exhaustion; Increased of quantitative immunoglobulin levels and subtype. |
Measure: | Progression-free Survival (PFS) |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | Progressive disease (PD), defined as ≥ 50% rise in lymphocyte count to > 5 x10^9/L, ≥ 50% increase in lymphadenopathy, ≥ 50% increase in liver or spleen size, Richter's transformation, or new cytopenias due to CLL. |
Measure: | Incidence of Richter's Transformation |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | H. Lee Moffitt Cancer Center and Research Institute |
Trial Keywords
- Lymphocytic
- Leukemia
- CLL
- Blood disease
- White blood cells
- Bone marrow disease
- Immunotherapy
Last Updated
August 4, 2021