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

NCT ID: NCT03605589

Last Updated: 2021-04-01

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-27
• Study Completion Date: 2022-01-31

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.

Detailed Description

Participants who meet study eligibility will receive or continue to receive blinatumomab by continuous IV infusion for 28 days and also receive pembrolizumab (by IV infusion over 30 minutes) on day 12 of cycle 1 and day 5 of cycle 2.

One cycle lasts 35 days and patients will receive 2 cycles of therapy.

Conditions

Leukemia, B-cell; Lymphoma, B-Cell

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Blinatumomab and Pembrolizumab

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.

Group Type: EXPERIMENTAL

Blinatumomab

Intervention Type: DRUG

Continuous IV infusion

Pembrolizumab

Intervention Type: DRUG

IV infusion

Interventions

Blinatumomab

Continuous IV infusion

Intervention Type: DRUG

Pembrolizumab

IV infusion

Intervention Type: DRUG

Other Intervention Names

Blincyto; Keytruda

Eligibility Criteria

Inclusion Criteria

• 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:
• 2nd 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's Hospital Medical Center, Cincinnati

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Erin Breese, MD. PhD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Medical Center, Cincinnati

Locations

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Countries

United States

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Other Identifiers

Pembro-EB-1701

Identifier Type: -

Identifier Source: org_study_id