Description:
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.
Title
- 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
Clinical Trial IDs
- ORG STUDY ID:
Pembro-EB-1701
- NCT ID:
NCT03605589
Conditions
- Leukemia, B-cell
- Lymphoma, B-Cell
Interventions
| Drug | Synonyms | Arms |
|---|
| Blinatumomab | Blincyto | Blinatumomab and Pembrolizumab |
| Pembrolizumab | Keytruda | Blinatumomab and Pembrolizumab |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| 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. | - Blinatumomab
- Pembrolizumab
|
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
| Maximum Eligible Age: | 40 Years |
| Minimum Eligible Age: | 1 Year |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Feasibility of combining pembrolizumab and blinatumomab (dose limiting toxicities) |
| Time Frame: | 2 cycles of therapy (70 days) |
| Safety Issue: | |
| Description: | Number of DLTs |
Secondary Outcome Measures
| Measure: | Disease response |
| Time Frame: | 2 cycles (70 days) |
| Safety Issue: | |
| Description: | Estimate of overall response rate (CR/CRh) |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Withdrawn |
| Lead Sponsor: | Children's Hospital Medical Center, Cincinnati |
Trial Keywords
- Blinatumomab
- Pembrolizumab
- CD19 positive
- Relapsed
- Refractory
Last Updated
April 1, 2021
