Pembro + Blina Combination in Pediatric and Young Adult Patients With Relapsed/Refractory Acute Leukemia or Lymphoma

NCT03605589 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: Pembro-EB-1701
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study combines the immune checkpoint inhibitor pembrolizumab with the BITE antibody blinatumomab for the treatment of relapsed/refractory pre-B cell ALL. Pembrolizumab at the proposed dosing schedule has been very well tolerated in adult studies, including elderly and unfit patients, as well as in pediatric patients. Both blinatumomab and pembrolizumab are FDA-approved for use in children as well as adults. Phase I/II trials in adult patients have demonstrated safety and activity of pembrolizumab in combination with multiple agents. In this trial, the combination of pembrolizumab and blinatumomab will be investigated for toxicity as well as possible synergy in the treatment of relapsed/refractory pre-B cell ALL. This is a single institution investigator-initiated pilot study designed to test the safety and feasibility of combining pembrolizumab and blinatumomab immunotherapies in children, adolescents, and young adults with CD19 positive hematologic malignancies. The investigator will define the toxicity profile of the combination in two safety strata based on whether or not a patient has had a prior allogeneic hematopoietic stem cell transplant (HSCT), as they hypothesize that the immune toxicities may differ between strata. In addition, the overall response rate (CR/CRh) to this therapy will be estimated. Additional biologic correlates will be conducted to delineate the effect of the combination therapy on the patient's leukemia/lymphoma and T-cell populations and how this may influence response to therapy.

Conditions

Leukemia, B-cell; Lymphoma, B-Cell

Keywords

Blinatumomab; Pembrolizumab; CD19 positive; Relapsed; Refractory

Outcome Measures

Primary Outcomes (2)

• Feasibility of combining pembrolizumab and blinatumomab (dose limiting toxicities)

  Number of DLTs

  2 cycles of therapy (70 days)

• Treatment related toxicities

  Number of related adverse events

  2 cycles of therapy (70 days)

Secondary Outcomes (1)

• Disease response

  2 cycles (70 days)

Study Arms (1)

Blinatumomab and Pembrolizumab

EXPERIMENTAL

Blinatumomab and Pembrolizumab will be given for 2 cycles (each cycle lasts 35 days). Blinatumomab administered as a continuous IV infusion. Patient Weight Greater Than or Equal to 45 kg (Fixed dose) Patient Weight Less Than 45 kg (BSA-based dose) Cycle 1 (Days 1-7): Patient Weight Greater Than or Equal to 45 kg: 9 mcg/day Patient Weight Less Than 45 kg: 5 mcg/m2/day Cycle 1(Days 8-28): Patient Weight Greater Than or Equal to 45 kg: 28 mcg/day Patient Weight Less Than 45 kg: 15 mcg/m2/day Cycle 2 (Days 1-28): Patient Weight Greater Than or Equal to 45 kg: 28 mcg/day Patient Weight Less Than 45 kg: 15 mcg/m2/day Pembrolizumab: 2 mg/kg (max dose 200 mg) administered as a 30 minute IV infusion on day 12 of cycle 1 and day 5 of cycle 2.

Drug: Blinatumomab; Drug: Pembrolizumab

Interventions

Blinatumomab DRUG

Continuous IV infusion

Also known as: Blincyto

Blinatumomab and Pembrolizumab

Pembrolizumab DRUG

IV infusion

Also known as: Keytruda

Blinatumomab and Pembrolizumab

Eligibility Criteria

• Age: 1 Year - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age 1-40
• Diagnosis of CD19 positive B-cell acute lymphoblastic leukemia (ALL) positive B-cell acute lymphoblastic leukemia (ALL) or CD19 positive B-cell lymphoma
• Patients with CD19 positive B-ALL must have greater than or equal to 5% lymphoblast in the bone marrow AND meet one of the following criteria:
• nd or greater relapse
• Any relapse after allo-HSCT
• Refractory disease
• Patients with CD19 positive relapsed/refractory lymphoma must be in 2nd or greater relapse or have refractory disease with the markers of disease burden
• Patients with CNS 1 or CNS 2 leukemia are eligible.Patients with CNS 3 leukemia are not eligible. However, patients with a history of CNS 3 status who have been sufficiently treated are eligible if currently CNS 1 or 2. Patients with an isolated CNS relapse are not eligible.
• Karnofsky performance level greater than or equal to 50 % for patients older than 16
• Lansky performance level greater than or equal to 50 % less than or equal to 16
• Patients recovered from acute toxicities from prior anti-cancer chemotherapy including HSCT, cytotoxic therapy, prior blinatumomab, biologic, immunotherapy, monoclonal antibody, XRT and corticosteroid therapy
• Patients with adequate hematological, renal, liver, cardiac, pulmonary and CNS organ functions
• Female participants of child bearing age must have negative pregnancy test, abstain or use contraception for 120 days after last dose of pembrolizumab

You may not qualify if:

• Patients with the following diagnoses: CNS 3 leukemia, CNS lymphoma, active GVHD, Downs Syndrome, CNS or testicular relapse, optic nerve or retinal involvement requiring radiation therapy
• Pregnant or breastfeeding
• Concomitant corticosteroids, immunosuppressive therapies, investigational drugs, anti-cancer agents
• Concurrent illnesses including: history of any grade autoimmune disorder, Grade 2 or higher hypothyroidism die to autoimmunity, uncontrolled infection, interstitial lung disease or pneumonitis
• Patients with other concurrent malignancies
• Patients who have received live vaccines within the last 30 days
• Patients with history of solid organ transplant

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

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MeSH Terms

Conditions

Leukemia, B-Cell; Lymphoma, B-Cell; Recurrence

Interventions

blinatumomab; 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; Lymphoma, Non-Hodgkin; Lymphoma; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Erin Breese, MD. PhD

  Children's Hospital Medical Center, Cincinnati

  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

Model Details: This is a pilot study to assess the safety, tolerability, and preliminary anti-tumor activity of the combination of pembrolizumab and blinatumomab in children and young adult patients with relapsed and/or refractory CD19 positive B-cell hematologic malignancies.

Study Record Dates

• First Submitted: July 20, 2018
• First Posted: July 30, 2018
• Study Start: September 27, 2018
• Primary Completion: August 1, 2021
• Study Completion: January 1, 2022
• Last Updated: April 1, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)