Clinical trial NCT03605589: 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
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Leukemia, B-cell
Lymphoma, B-Cell
Keywords: Blinatumomab
Pembrolizumab
CD19 positive
Relapsed
Refractory
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
First posted: 2018-07-30
Enrollment: 0
Sex: ALL
Minimum age (years): 1
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Feasibility of combining pembrolizumab and blinatumomab (dose limiting toxicities)
timeFrame: 2 cycles of therapy (70 days)
measure: Treatment related toxicities
timeFrame: 2 cycles of therapy (70 days)
Secondary outcomes:
measure: Disease response
timeFrame: 2 cycles (70 days)
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Erin Breese, MD. PhD
role: PRINCIPAL_INVESTIGATOR
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