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

NCT03160079 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 161287/UCHMC1504
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 4

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 (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).

Conditions

B-Cell Acute Lymphoblastic Leukemia, Adult

Keywords

blinatumomab; pembrolizumab; MK-3475; relapsed; refractory; B-lineage acute lymphoblastic leukemia; ALL

Outcome Measures

Primary Outcomes (1)

• Best Overall Response Rate (ORR)

  Best overall response rate (ORR) with the combination of blinatumomab and pembrolizumab in adult subjects with relapsed or refractory B-cell acute lymphoblastic leukemia will be defined as the Complete Response (CR) rate plus the Complete Response with Hematologic Recovery (CRh) rate after treatment of combination therapy. According to the National Comprehensive Cancer Network (NCCN) Guidelines for Acute Lymphoblastic Leukemia (version 1, 2015), CR is defined as \<5% lymphoblast in the bone marrow without evidence of circulating lymphoblasts or extramedullary disease. CRh is defined as for CR except with platelet count \>50,000/microliter, hemoglobin \>7 g/dL, and neutrophil (ANC) \>500/microliter.

  28 weeks

Secondary Outcomes (4)

• Complete Response Rate (CR)

  28 weeks

• Minimal Residual Disease (MRD) Negativity Rate in Subjects Achieving a CR or CRh

  28 weeks

• 2 Year Relapse-free Survival Rate

  2 years

• 2-year Overall Survival Rate

  2 years

Study Arms (1)

Blinatumomab + Pembrolizumab

EXPERIMENTAL

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 Other Names: Blincyto 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) Other Names: * Keytruda * MK-3475

Drug: blinatumomab; Drug: pembrolizumab

Interventions

blinatumomab DRUG

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

Also known as: Blincyto

Blinatumomab + Pembrolizumab

pembrolizumab DRUG

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)

Also known as: Keytruda, MK-3475

Blinatumomab + Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Relapsed or refractory B-lineage acute lymphoblastic leukemia (B-ALL) having received at least 1 prior line of therapy
• Philadelphia chromosome positive (Ph+), or Breakpoint Cluster Region Protein-Abelson Murine Leukemia Viral Oncogene Homolog 1 (BCR-ABL1) positive B-lineage ALL must have failed at least 1 second or third generation tyrosine kinase inhibitor (TKI) or be intolerant to TKIs
• Greater than 50% lymphoblasts on screening bone marrow aspirate or biopsy
• Adequate organ function
• Women of child-bearing potential and men with partners of child-bearing potential must agree to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication.
• A woman of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
• Male subjects must agree to use a latex condom during sexual contact with females of childbearing potential even if they have had a successful vasectomy starting with the first dose of study therapy through 120 days after the last dose of study therapy.

You may not qualify if:

• Allogeneic hematopoietic cell transplantation within 5 years of study drug administration
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) or Granulocyte Colony-Stimulating Factor (G-CSF) use within 2 weeks of study treatment and throughout the study
• Prior checkpoint inhibitor therapy including anti Programmed Death Receptor 1 (anti-PD1), anti-PD-L1, anti-CTLA4 (cytotoxic T-lymphocyte-associated protein 4), anti tumor necrosis factor receptor superfamily, member 9 (anti-CD137), or anti-PD-L2 therapy
• Active Central Nervous System (CNS) or testicular involvement by leukemia
• History of neurologic disorder
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
• Burkitt lymphoma/leukemia
• Has a diagnosis of congenital immunodeficiency
• Has a known history of active Bacillus Tuberculosis (TB)
• Known Human Immunodeficiency Virus (HIV) infection
• Active hepatitis B or hepatitis C infection
• Has received a live vaccine within 30 days prior to first dose
• 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 120 days after the last dose of trial treatment.
• History of autoimmune disease

Sponsors & Collaborators

• University of California, San Diego: lead
• Merck Sharp & Dohme LLC: collaborator
• Amgen: collaborator

Study Sites (4)

UCSF Fresno Community Cancer Institute

Clovis, California, 93611, United States

Location

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

UC Irvine Health Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

Location

UCSF Comprehensive Cancer Center

San Francisco, California, 94143, United States

Location

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  BACKGROUND

MeSH Terms

Conditions

Burkitt Lymphoma; Recurrence

Interventions

blinatumomab; pembrolizumab

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

There have been several limitations for reporting these results. The original PI left University of California San Diego (UCSD) and remained the Investigational New Drug (IND) holder, but UCSD is listed as the responsible reporting party on CT.gov. The final data analysis was not received until recently because of extensive technical and logistical issues.

Results Point of Contact

• Title: Dr. James Mangan
• Organization: University of California, San Diego, Moores Cancer Center

jmangan@health.ucsd.edu

858-822-6600

Study Officials

• James K Mangan, M.D., P.h.D.

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Clinical Professor of Medicine

Study Record Dates

• First Submitted: May 16, 2017
• First Posted: May 19, 2017
• Study Start: August 4, 2017
• Primary Completion: December 21, 2021
• Study Completion: June 23, 2023
• Last Updated: November 10, 2025
• Results First Posted: November 10, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)