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

Primary Purpose

Leukemia, B-cell, Lymphoma, B-Cell

Status
Withdrawn
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Blinatumomab
Pembrolizumab
Sponsored by
Children's Hospital Medical Center, Cincinnati
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia, B-cell focused on measuring Blinatumomab, Pembrolizumab, CD19 positive, Relapsed, Refractory

Eligibility Criteria

1 Year - 40 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Cincinnati Children's Hospital Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Blinatumomab and Pembrolizumab

Arm Description

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.

Outcomes

Primary Outcome Measures

Feasibility of combining pembrolizumab and blinatumomab (dose limiting toxicities)
Number of DLTs
Treatment related toxicities
Number of related adverse events

Secondary Outcome Measures

Disease response
Estimate of overall response rate (CR/CRh)

Full Information

First Posted
July 20, 2018
Last Updated
March 30, 2021
Sponsor
Children's Hospital Medical Center, Cincinnati
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1. Study Identification

Unique Protocol Identification Number
NCT03605589
Brief Title
Pembro + Blina Combination in Pediatric and Young Adult Patients With Relapsed/Refractory Acute Leukemia or Lymphoma
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Withdrawn
Why Stopped
Lack of enrollment due to the availability of other novel salvage therapies for relapsed/refractory B-ALL.
Study Start Date
September 27, 2018 (Actual)
Primary Completion Date
August 2021 (Anticipated)
Study Completion Date
January 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Hospital Medical Center, Cincinnati

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, B-cell, Lymphoma, B-Cell
Keywords
Blinatumomab, Pembrolizumab, CD19 positive, Relapsed, Refractory

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
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)
Allocation
N/A
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Blinatumomab and Pembrolizumab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Blinatumomab
Other Intervention Name(s)
Blincyto
Intervention Description
Continuous IV infusion
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda
Intervention Description
IV infusion
Primary Outcome Measure Information:
Title
Feasibility of combining pembrolizumab and blinatumomab (dose limiting toxicities)
Description
Number of DLTs
Time Frame
2 cycles of therapy (70 days)
Title
Treatment related toxicities
Description
Number of related adverse events
Time Frame
2 cycles of therapy (70 days)
Secondary Outcome Measure Information:
Title
Disease response
Description
Estimate of overall response rate (CR/CRh)
Time Frame
2 cycles (70 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Erin Breese, MD. PhD
Organizational Affiliation
Children's Hospital Medical Center, Cincinnati
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
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Pembro + Blina Combination in Pediatric and Young Adult Patients With Relapsed/Refractory Acute Leukemia or Lymphoma

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