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

NCT03512405 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 19017NCI-2018-00526
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Incidence of toxicity (Phase 1)

  Will be graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 5

  Up to 42 days

• Response (Phase 2)

  Response will be defined as complete response (CR)/CR with incomplete hematologic recovery (CRi) based on the National Comprehensive Cancer Network guidelines on acute lymphoblastic leukemia version 1 2017 response criteria. Evaluated using Simon two-stage optimal design

  Up to 1 year

Secondary Outcomes (9)

• Incidence of adverse events

  Up to 1 year

• Duration of remission

  From the date of first documented response (CR/CRi) up to 1 year

• Time to response

  From date of first dose of study drug up to 1 year

• Overall survival

  From date of first dose of study drug up to 1 year

• Event-free survival

  From date of first dose of study drug up to 1 year

Study Arms (1)

Treatment (pembrolizumab, blinatumomab)

EXPERIMENTAL

Participants receive pembrolizumab IV over 30 minutes on day 15 of course 1 and days 1 and 22 of courses 2 -4, and blinatumomab IV on days 1-28. Treatment repeats every 35-42 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Biological: Blinatumomab; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

Interventions

Blinatumomab BIOLOGICAL

Given IV

Also known as: Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody, Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103, Blincyto, MEDI-538, MT-103

Treatment (pembrolizumab, blinatumomab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (pembrolizumab, blinatumomab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (pembrolizumab, blinatumomab)

Eligibility Criteria

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

You may qualify if:

• Previously treated ALL including philadelphia chromosome (BCR-Ab1) positive ALL who meet all of the following criteria:
• Diagnosis of CD19-positive B-cell ALL based on the flow cytometry and histology
• Previously treated subjects with primary refractory disease OR after first or subsequent relapse
• Subjects with detectable lymphoblasts in bone marrow (BM) or extramedullary disease (EMD) that is radiographically measurable and amenable to repeat biopsies
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Left ventricular ejection fraction (LVEF) \> 45%
• Pulmonary function tests diffusing capacity of the lungs for carbon monoxide (DLCO) (adjusted for hemoglobin) \> 50% predicted
• Serum creatinine =\< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) \>= 60 ml/min for subject with creatinine levels \> 1.5 X institutional ULN
• Serum total bilirubin =\< 1.5 X ULN OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 ULN
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine transaminase (serum glutamic pyruvic transaminase \[SGPT\]) =\< 2.5 X ULN OR =\< 5 X ULN for subjects with liver metastases
• Albumin \>= 2.5 mg/dL
• International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
• Activated partial thromboplastin time (aPTT) =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Beta human chorionic gonadotropin (beta HCG) negative
• Human immunodeficiency virus (HIV): negative HIV antibody / polymerase chain reaction (PCR)

You may not qualify if:

• Diagnosis of mature B-cell ALL (Burkitt's leukemia) according to World Health Organization (WHO) classification, or lymphoid blast crisis of chronic myelogenous leukemia (CML)
• A life threatening illness, medical condition or organ system dysfunction which, in the investigators' opinion, could compromise the subject's safety or interfere with the absorption or metabolism of pembrolizumab
• Active or symptomatic central nervous system (CNS) disease
• For study purposes, a subject will not be considered as having active CNS disease if the subject has documentation of prior CNS disease and has received prior treatment (IT or radiation) and is:
• Asymptomatic for the last 28 days prior to screening and
• Has documented at least 2 negative cerebrospinal fluid (CSF) cytology (which must include 1 lumbar puncture \[LP\] within the study screening window)
• Uncontrolled undercurrent illness including but not limited to unstable angina pectoris or psychiatric illness/social situations that would limit compliance with study requirements; subjects with active infection are permitted to enroll provided that the infection is documented to be under control
• History of myelodysplastic syndrome or organ transplantation
• History of non-lymphoid malignancy except for the following:
• Adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requirement only hormonal therapy and with normal prostate specific antigen for \> 1 year prior to the start of pembrolizumab, or any other cancer that has been in complete remission without treatment for \>= 5 years prior to enrollment
• Known hypersensitivity or intolerance to any of the active substance or excipients in the formulations for pembrolizumab and blinatumomab
• Ongoing drug-induced liver injury, chronic active hepatitis C (HCV), chronic active hepatitis B (HBV), HIV, alcoholic liver disease, non-alcoholic steatohepatitis, cirrhosis of the liver, or portal hypertension
• Prior allogeneic bone marrow transplantation
• Pregnancy or breastfeeding
• Has known history of, or any evidence of active, non-infectious pneumonitis

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

blinatumomab; N,N-dicyclohexyl-isoborneol-10-sulfonamide; pembrolizumab

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Lihua Budde

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2018
• First Posted: April 30, 2018
• Study Start: August 2, 2019
• Primary Completion: November 11, 2025
• Study Completion: November 11, 2025
• Last Updated: May 30, 2025

Record last verified: 2025-05

Locations

US (1)