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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03605589
Recruitment Status : Withdrawn (Lack of enrollment due to the availability of other novel salvage therapies for relapsed/refractory B-ALL.)
First Posted : July 30, 2018
Last Update Posted : April 1, 2021
Sponsor:
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

Study Description
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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.


Condition or disease Intervention/treatment Phase
Leukemia, B-cell Lymphoma, B-Cell Drug: Blinatumomab Drug: Pembrolizumab Phase 1

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: 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.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study of Blinatumomab in Combination With a PD1 Inhibitor, Pembrolizumab, in Pediatric and Young Adult Patients With Relapsed/Refractory CD19 Positive B-cell Acute Leukemia or Lymphoma
Actual Study Start Date : September 27, 2018
Estimated Primary Completion Date : August 2021
Estimated Study Completion Date : January 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leukemia Lymphoma

Arms and Interventions
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Arm Intervention/treatment
Experimental: 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.

 Drug: Blinatumomab
Continuous IV infusion
Other Name: Blincyto

Drug: Pembrolizumab
IV infusion
Other Name: Keytruda


Outcome Measures
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Primary Outcome Measures :
  1. Feasibility of combining pembrolizumab and blinatumomab (dose limiting toxicities) [ Time Frame: 2 cycles of therapy (70 days) ]
    Number of DLTs

  2. Treatment related toxicities [ Time Frame: 2 cycles of therapy (70 days) ]
    Number of related adverse events


Secondary Outcome Measures :
  1. Disease response [ Time Frame: 2 cycles (70 days) ]
    Estimate of overall response rate (CR/CRh)


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   1 Year to 40 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03605589


Locations
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United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
Investigators
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Principal Investigator: Erin Breese, MD. PhD Children's Hospital Medical Center, Cincinnati
More Information
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Publications:

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Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT03605589    
Other Study ID Numbers: Pembro-EB-1701
First Posted: July 30, 2018    Key Record Dates
Last Update Posted: April 1, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Children's Hospital Medical Center, Cincinnati:
Blinatumomab
Pembrolizumab
CD19 positive
Relapsed
Refractory
Additional relevant MeSH terms:
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Lymphoma
Leukemia
Lymphoma, B-Cell
Leukemia, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
 Immune System Diseases
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Pembrolizumab
Blinatumomab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action