Clinical Trials /

Ibrutinib and PD-1 Blockade in High Risk Lymphocytic Leukemia

NCT03514017

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.

Related Conditions:
  • Chronic Lymphocytic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

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

DrugSynonymsArms
PembrolizumabKeytruda®Pembrolizumab and Ibrutinib
IbrutinibImbruvica®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

NameTypeDescriptionInterventions
Pembrolizumab and IbrutinibExperimentalTreatment 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.
  • Pembrolizumab
  • Ibrutinib

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

February 5, 2020