A Phase 1/2 interventional study of blinatumomab and pembrolizumab in B-Cell Acute Lymphoblastic Leukemia, Adult, sponsored by University of California, San Diego. Completed at 4 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-11-10.
Sponsored by University of California, San Diego · Phase 1/2, Interventional, and Treatment
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).
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
392 studies on the registry are indexed under Burkitt Lymphoma; 114 are open to participants now.
This study's enrollment of 16 is below the median of 41 across 354 interventional studies indexed under Burkitt Lymphoma.
Browse Burkitt Lymphoma studies →University of California, San Diego is the lead sponsor of 958 studies on the registry; 191 are open to participants now.
Of its 110 completed or terminated interventional studies of FDA-regulated products, 70 (64%) have results posted.
Counted across the registry records on this site, refreshed daily.
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:
Exclusion Criteria:
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
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
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
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.
Time frame: 28 weeks
Complete Response Rate (CR)
CR is defined as \<5% lymphoblast in the bone marrow without evidence of circulating lymphoblasts or extramedullary disease.
Time frame: 28 weeks
Minimal Residual Disease (MRD) Negativity Rate in Subjects Achieving a CR or CRh
Minimal residual disease (MRD) negativity in subjects achieving a CR or CRh will be defined as less than 0.01% residual lymphoblasts by multiparameter flow cytometry.
Time frame: 28 weeks
2 Year Relapse-free Survival Rate
The number of patients achieving relapse free survival at 2 years. Relapse-free survival (RFS) will be defined as the time from achieving CR or CRh to relapse defined as the reappearance of lymphoblasts in bone marrow or blood at \>5% of cells or reappearance of extramedullary disease.
Time frame: 2 years
2-year Overall Survival Rate
The number of participants achieving survival at 2 years. 2-year overall survival (OS) will be defined as the time from starting study therapy to death from any cause.
Time frame: 2 years
| Milestone | Blinatumomab + Pembrolizumab | Blinatumomab Only |
|---|---|---|
| Started | 12 | 4 |
| Completed course 1 | 8 | 4 |
| Completed course 2 | 5 | 0 |
| Completed course 3 | 3 | 0 |
| Completed course 4 | 1 | 0 |
| Completed course 5 | 1 | 0 |
| Completed | 8 | 4 |
| Not completed | 4 | 0 |
| Withdrew: Adverse event | 2 | 0 |
| Withdrew: Disease progression | 1 | 0 |
| Withdrew: Physician decision | 1 | 0 |
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.
| Participants | Blinatumomab + Pembrolizumab | Blinatumomab Only |
|---|---|---|
| Complete Response (CR) | 6 | 0 |
| Complete Response with Hematologic Recovery | 1 | 0 |
| Partial Response | 1 | 0 |
| Refractory | 4 | 1 |
| Not Evaluated | 0 | 3 |
CR is defined as \<5% lymphoblast in the bone marrow without evidence of circulating lymphoblasts or extramedullary disease.
| Participants | Blinatumomab + Pembrolizumab | Blinatumomab Only |
|---|---|---|
| Complete Response Rate (CR) | 6 | 0 |
Minimal residual disease (MRD) negativity in subjects achieving a CR or CRh will be defined as less than 0.01% residual lymphoblasts by multiparameter flow cytometry.
| Participants | Blinatumomab + Pembrolizumab | Blinatumomab Only |
|---|---|---|
| MRD negativity | 6 | 0 |
| MRD not evaluable | 1 | 2 |
The number of patients achieving relapse free survival at 2 years. Relapse-free survival (RFS) will be defined as the time from achieving CR or CRh to relapse defined as the reappearance of lymphoblasts in bone marrow or blood at \>5% of cells or reappearance of extramedullary disease.
| participants | Blinatumomab + Pembrolizumab |
|---|---|
| 2 Year Relapse-free Survival Rate | 2 (1 to 7) |
The number of participants achieving survival at 2 years. 2-year overall survival (OS) will be defined as the time from starting study therapy to death from any cause.
| participants | Blinatumomab + Pembrolizumab | Pembrolizumab Only |
|---|---|---|
| 2-year Overall Survival Rate | 3 (2.55 to 4.95) | 1 (.85 to 1.65) |
Collected over 8 months (7 months on treatment and 30 days monitoring post last dose). Note that overall survival was monitored for 2 years, but Adverse Events were not monitored after 8 months.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Blinatumomab + Pembrolizumab | 1/12 (8.3%) | 4/12 (33.3%) | 12/12 (100%) |
| Blinatumomab Only | 0/4 (0%) | 1/4 (25%) | 4/4 (100%) |
| Event | Blinatumomab + Pembrolizumab | Blinatumomab Only |
|---|---|---|
| Intracranial Hemorrhage/HematomaNervous system disorders | 1/12 | 1/4 |
| Cytokine Release SyndromeImmune system disorders | 1/12 | 0/4 |
| FeverGeneral disorders | 1/12 | 0/4 |
| SeizureNervous system disorders | 1/12 | 0/4 |
| HypoxiaRespiratory, thoracic and mediastinal disorders | 1/12 | 0/4 |
| Acute Disseminating Intravascular CoagulationBlood and lymphatic system disorders | 1/12 | 0/4 |
| Macrophage Activation SyndromeBlood and lymphatic system disorders | 1/12 | 0/4 |
| Neck EdemaGeneral disorders | 1/12 | 0/4 |
| Event | Blinatumomab + Pembrolizumab | Blinatumomab Only |
|---|---|---|
| NEUTROPHIL COUNT DECREASEDInvestigations | 10/12 | 0/4 |
| Aspartate Aminotransaminase IncreasedInvestigations | 4/12 | 3/4 |
| Cytokine Release SyndromeImmune system disorders | 7/12 | 3/4 |
| HeadacheNervous system disorders | 9/12 | 1/4 |
| Abdominal PainGastrointestinal disorders | 2/12 | 2/4 |
| AnorexiaMetabolism and nutrition disorders | 3/12 | 2/4 |
| ConfusionPsychiatric disorders | 0/12 | 2/4 |
| FatigueGeneral disorders | 5/12 | 2/4 |
| FeverGeneral disorders | 6/12 | 2/4 |
| Fluid Volume OverloadEndocrine disorders | 0/12 | 2/4 |
Demographics were recorded for all patients who enrolled
| Age, Categorical(Participants) | Blinatumomab + Pembrolizumab | Blinatumomab Only | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 11 | 3 | 14 |
| >=65 years | 1 | 1 | 2 |
| Sex: Female, Male(Participants) | Blinatumomab + Pembrolizumab | Blinatumomab Only | Total |
|---|---|---|---|
| Female | 8 | 2 | 10 |
| Male | 4 | 2 | 6 |
| Ethnicity (NIH/OMB)(Participants) | Blinatumomab + Pembrolizumab | Blinatumomab Only | Total |
|---|---|---|---|
| Hispanic or Latino | 9 | 2 | 11 |
| Not Hispanic or Latino | 3 | 2 | 5 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Blinatumomab + Pembrolizumab | Blinatumomab Only | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 1 | 1 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 1 | 1 | 2 |
| White | 10 | 1 | 11 |
| More than one race | 1 | 0 | 1 |
| Unknown or Not Reported | 0 | 1 | 1 |
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University of California, San Diego