NCT03160079

Blinatumomab & Pembrolizumab for Adults With Relapsed/Refractory B-cell ALL With High Marrow Lymphoblasts

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 Percentage

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 16 (actual)
• Sponsor: University of California, San Diego · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a Phase I/II study of blinatumomab in combination with pembrolizumab in adult patients with relapsed or refractory B-lineage ALL (B-ALL). The primary objective of this study is to determine if the addition of pembrolizumab to blinatumomab improves the Complete Response Rate (CR) and Complete Remission with Partial Hematologic Recovery (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 description

This is a Phase I/II study of blinatumomab in combination with pembrolizumab in adult patients with relapsed or refractory B-lineage ALL (B-ALL). The primary objective of this study is to determine if the addition of pembrolizumab to blinatumomab improves the Complete Response Rate (CR) and Complete Remission with Partial Hematologic Recovery (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). Mechanisms of resistance to blinatumomab are not well understood although inhibition of or suboptimal T-cell activation may play an important role. Programmed Death-Ligand 1 (PD-L1) and Programmed Death-Ligand 2 (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 Programmed Death 1 (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 intervention. Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the Immunoglobulin G4 (IgG4/kappa) isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. The study will be conducted in 2 stages: Stage 1 is to ensure safety of pembrolizumab in combination with blinatumomab. Stage 2 of the study will include an expansion cohort of up to 21 additional subjects (for a total of 24 subjects) to evaluate the efficacy of the combination of blinatumomab and pembrolizumab in adults with relapsed/refractory B-cell ALL

Conditions

• B-Cell Acute Lymphoblastic Leukemia, Adult

Interventions

Type	Name	Description
DRUG	blinatumomab	Cycle 1 Blinatumomab Day 1-7 Continuous IV infusion for 28 days (9 mcg/day) Blinatumomab Day 8-28 Continuous IV infusion for 28 days (28 mcg/day) Cycle 2-5 Blinatumomab Day 1-28 Continuous IV infusion for 28 days (28 mcg/day) Cycle length 42 days
DRUG	pembrolizumab	Cycle 1 Pembrolizumab Day 15 and 36 IV infusion over 30 minutes (200mg) Cycle 2-5 Pembrolizumab Day 15 and 36 IV infusion over 30 minutes (200mg)

Timeline

• Start date: 2017-08-04
• Primary completion: 2021-12-21
• Completion: 2023-06-23
• First posted: 2017-05-19
• Last updated: 2025-11-10
• Results posted: 2025-11-10

Locations

4 sites across 1 country: United States

Regulatory

• FDA-regulated drug study