NCT03512405

Pembrolizumab and Blinatumomab in Treating Participants With Recurrent or Refractory Acute Lymphoblastic Leukemia

A Phase 1/2 Trial of Pembrolizumab in Combination With Blinatumomab in Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 36 (estimated)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I/II studies the side effects of pembrolizumab and blinatumomab and to see how well they work in treating participants with acute lymphoblastic leukemia that has come back or has not responded to the treatment. Monoclonal antibodies, such as pembrolizumab and blinatumomab, may interfere with the ability of tumor cells to grow and spread.

Detailed description

PRIMARY OBJECTIVES: I. Assess the safety and tolerability of combination immunotherapy with blinatumomab and pembrolizumab by evaluation of toxicities including: type, frequency, severity, attribution, time course and duration. (Phase 1) II. Determine the recommended phase 2 schedule of combination immunotherapy with pembrolizumab and blinatumomab. (Phase 1) III. Evaluate the anti-leukemia activity of combination immunotherapy blinatumomab and pembrolizumab as assessed by overall response rate (complete response \[CR\] or CR with incomplete recovery \[CRi\]). (Phase 2) SECONDARY OBJECTIVES: I. Estimate time to response (CR or CRi) and response duration. (Phase 2) II. Estimate overall survival and event-free survival. (Phase 2) III. Determine the number and proportion of patients who underwent hematopoietic stem cell transplantation (HSCT) after treatment of pembrolizumab and blinatumomab. (Phase 2) IV. Determine the number and proportion of patients who receive pembrolizumab maintenance and the proportion continuing for up to 1 year. (Phase 2) V. Estimate the minimal residual disease rate. (Phase 2) CORRELATIVE OBJECTIVES: I. Explore evolution of T cell subsets at various points in treatment (T naive, T effector, T effector memory, T central memory, CD4, CD8). (Phase 2) II. Evaluate PD-L1 expression levels on acute lymphoblastic leukemia (ALL) blasts and blasts counts overtime. (Phase 2) III. Evaluate PD-1/PD-L1 expression on subsets of T cells. (Phase 2) IV. Evaluate the clonal evolution of leukemic blasts in response to treatment. (Phase 2) OUTLINE: Participants receive pembrolizumab intravenously (IV) over 30 minutes on day 15 of cycle 1 and days 1 and 22 of cycles 2 -5, and blinatumomab IV on days 1-28. Treatment repeats every 35-42 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response have the option to receive blinatumomab IV for up to 4 additional cycles. After completion of study treatment, participants are followed up at 30 days and then every 3 months for 1 year.

Conditions

• CD19 Positive
• Philadelphia Chromosome Positive
• Recurrent Acute Lymphoblastic Leukemia
• Refractory Acute Lymphoblastic Leukemia

Interventions

Type	Name	Description
BIOLOGICAL	Blinatumomab	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
BIOLOGICAL	Pembrolizumab	Given IV

Timeline

• Start date: 2019-08-02
• Primary completion: 2025-11-11
• Completion: 2025-11-11
• First posted: 2018-04-30
• Last updated: 2025-05-30

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study