Clinical Trial: Blinatumomab and Pembrolizumab for Adults With Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia With High Marrow Lymphoblasts

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: A Phase I/II Study of Blinatumomab in Combination With Pembrolizumab (MK-3475) for Adults With Relapsed or Refractory B-lineage Acute Lymphoblastic Leukemia With High Bone Marrow Lymphoblast Percentag

Brief Summary: This is a Phase I/II study of blinatumomab in combination with pembrolizumab in adult patients with relapsed or refractory B-lineage ALL The primary objective of this study is to determine if the addition of pembrolizumab to blinatumomab improves the overall response rate (CR+ CRh) relative to blinatumomab alone in adult subjects with relapsed or refractory B-cell acute lymphoblastic leukemia with high bone marrow lymphoblast percentage (>50% lymphoblasts).

Detailed Summary:

This is a Phase I/II study of blinatumomab in combination with pembrolizumab in adult patients with relapsed or refractory B-lineage ALL The primary objective of this study is to determine if the addition of pembrolizumab to blinatumomab improves the overall response rate (CR+ CRh) relative to blinatumomab alone in adult subjects with relapsed or refractory B-cell acute lymphoblastic leukemia with high bone marrow lymphoblast percentage.

Mechanisms of resistance to blinatumomab are not well understood although inhibition of or suboptimal T-cell activation may play an important role. PD-L1 and PD-L2 expression and upregulation in lymphoblasts and the bone marrow microenvironment at baseline and in response to cytokines including those released upon blinatumomab exposure may inhibit T-cell function through the PD-1 receptor and lead to resistance to blinatumomab. The investigators hypothesize that part of the resistance to therapy with blinatumomab is mediated by the exuberant cytokine release seen with higher disease burden leading to increased expression of PD-L1 and PD-L2. Enhancing T-cell activity through use of the PD-1 inhibitor pembrolizumab is predicted to augment the activity of blinatumomab and convert more patients to complete remission and prolong remission durations. This study will also act to expand knowledge of PD-L1 and PD-L2 dynamics in response to blinatumomab. It will also be a paradigm for the addition of checkpoint inhibitors to therapy with bifunctional T-cell engaging antibodies currently in development for targeting other liquid and solid tumors.

The PD-1 receptor-ligand interaction is a major pathway hijacked by tumors to suppress immune control. This suggests that the PD-1/PD-L1 pathway plays a critical role in tumor immune evasion and should be considered as an attractive target for therapeutic in
Sponsor: Matthew Wieduwilt, M.D., Ph.D.

Current Primary Outcome: Overall Response Rate (ORR) [ Time Frame: 28 weeks ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Complete Response Rate (CR) [ Time Frame: 28 weeks ]
  • Minimal residual disease (MRD) negativity rate in subjects achieving a CR or CRh [ Time Frame: 28 weeks ]
  • 2 year relapse-free survival [ Time Frame: 2 years ]
  • 2-year overall survival [ Time Frame: 2 years ]
  • Number of participants with treatment-related adverse events as assessed by NCI CTCAE v4.0 [ Time Frame: 4 years ]
    Safety and tolerability of blinatumomab in combination with pembrolizumab


Original Secondary Outcome: Same as current

Information By: University of California, San Diego

Dates:
Date Received: May 16, 2017
Date Started: August 2017
Date Completion: August 2022
Last Updated: May 17, 2017
Last Verified: May 2017