Blinatumomab After TCR Alpha Beta/CD19 Depleted HCT

NCT04746209 | Recruiting Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: Blina Part 2
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This trial will assess the feasibility of alpha/beta T-cell and B-cell depleted allogeneic hematopoietic cell transplantation (HCT) followed by blinatumomab therapy for high-risk B cell acute lymphoblastic leukemia (ALL) as a means of reducing rates of subsequent relapse and improving survival, while also minimizing treatment-related morbidity/ mortality and late effects. The conditioning regimens will be dependent on the patient's minimal residual disease (MRD) status prior to HCT using high throughput sequencing.

Conditions

B-cell Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; B-Cell ALL, Childhood

Outcome Measures

Primary Outcomes (1)

• Percentage of patients who are able to receive the blinatumomab infusion [Feasibility]

  Percentage of patients who are able to receive the blinatumomab infusion at day +100 post-HCT and complete a minimum of 14/28 planned days

  Day +100 post-HCT

Secondary Outcomes (12)

• Cumulative incidence of treatment-related adverse events [Tolerability]

  Day of HCT to Day +180 post-HCT

• Overall Survival

  Day of HCT to 1 year post-HCT

• Disease Free Survival

  Day of HCT to 1 year post-HCT

• Engraftment

  Day +100 and +1 year post-HCT

• Primary Graft Failure

  Day +28 and + 1 year post-HCT

Other Outcomes (3)

• Analysis of immune cell phenotyping

  Days +19, +91, +135 and +180 post-HCT

• Functional assessment of lymphocyte subsets

  Days +19, +91, +135 and +180 post-HCT

• Serum cytokine analysis

  Days +19, +91, +135 and +180 post-HCT

Study Arms (2)

Alpha/beta T-cell and B-cell Depleted, Myeloablative HCT

EXPERIMENTAL

Patients who are MRD Negative by Flow cytometry but are MRD Positive by High Throughput Sequencing, will receive a myeloablative conditioning regimen which includes total body irradiation (TBI) followed by an alpha/beta T-cell and B-cell depleted transplant. They will also receive a 28 day continuous infusion of blinatumomab starting on Day 100 post-transplant in the absence of significant ongoing GVHD.

Device: Alpha/Beta T-cell and B-cell depleted HCT; Drug: Blinatumomab

Alpha/beta T-cell and B-cell Depleted, Reduced Intensity HCT

EXPERIMENTAL

Patients who are MRD Negative by Flow cytometry and are MRD Negative by High Throughput Sequencing, will receive a reduced intensity conditioning regimen followed by an alpha/beta T-cell and B-cell depleted transplant. They will also receive a 28 day continuous infusion of blinatumomab starting on Day 100 post-transplant in the absence of significant ongoing GVHD.

Device: Alpha/Beta T-cell and B-cell depleted HCT; Drug: Blinatumomab

Interventions

Alpha/Beta T-cell and B-cell depleted HCT DEVICE

Device: Alpha/Beta T-cell and B-cell depletion

Alpha/beta T-cell and B-cell Depleted, Myeloablative HCT; Alpha/beta T-cell and B-cell Depleted, Reduced Intensity HCT

Blinatumomab DRUG

28 day continuous infusion given on Day 100 post-HCT if no significant ongoing GVHD

Also known as: Blincyto

Alpha/beta T-cell and B-cell Depleted, Myeloablative HCT; Alpha/beta T-cell and B-cell Depleted, Reduced Intensity HCT

Eligibility Criteria

• Age: Up to 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis of B-ALL with no evidence of minimal residual disease in the bone marrow by multi-parameter flow cytometry (FC-MRD negative, \<0.01%) and meet at least one of the following:
• In remission after first relapse or greater (≥ CR2)
• Very-high risk biology ALL that is proceeding to HCT in first remission (e.g. Induction failure, Severe-hypodiploidy, Ph-like ALL)
• First remission with persistent disease identified as end of consolidation (EOC) MRD \> 0.01%.
• Patients must have an available unrelated or haploidentical donor
• Age ≤ 25 years at time of study enrollment
• Karnofsky Performance Status ≥ 60% for patients 16 years and older and Lansky Play Score ≥ 60 for patients under 16 years of age
• Have acceptable organ function as defined within 14 days of study registration: Renal: creatinine clearance or radioisotope GFR ≥ 60 mL/min/1.73m2 Hepatic: ALT \< 5 x upper limit of normal (ULN) and total bilirubin ≤ 3 mg/dL Cardiac: left ventricular ejection fraction ≥ 40% by ECHO/MUGA Pulmonary: No evidence of dyspnea at rest. No supplemental oxygen requirement. If measured, carbon monoxide diffusion capacity (DLCO) \> 50%. Central Nervous System: Based on clinical exam, no concern for/evidence of active CNS infection. Patients with fully treated prior CNS infections are eligible. Patients with seizure disorders may be enrolled if seizures are well-controlled on anticonvulsant therapy.
• Patients who have experienced their relapse after HCT are eligible, provided they have no evidence of acute or chronic Graft-versus-Host Disease (GVHD) and are off all transplant immune suppression therapy for at least 7-days (e.g. steroids, cyclosporine, tacrolimus). Steroid therapy for non-GVHD and/or non-leukemia therapy is acceptable.
• Immunotherapy: At least 42 days after the completion of any type of immunotherapy aside from blinatumomab (e.g. tumor vaccines or CAR T-cell therapy).
• XRT: Cranial or craniospinal XRT is prohibited during protocol therapy. ≥ 90 days must have elapsed if prior TBI, cranial or craniospinal XRT
• Sexually active females of child bearing potential must agree to use adequate contraception (diaphragm, birth control pills, injections, intrauterine device \[IUD\], surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration of treatment and for 2 months after the completion of blinatumomab therapy. Sexually active men must agree to use barrier contraceptive for the duration of treatment and for 2 months after the completion of blinatumomab therapy.
• Voluntary written consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
• All patients enrolled in this study must have been enrolled in the Blinatumomab Bridging Therapy (BBT) Trial

You may not qualify if:

• Active extramedullary disease or presence of chloromatous disease.
• Receiving concomitant chemotherapy, radiation therapy; immunotherapy or other anti-cancer therapy for treatment of disease other than is specified in the protocol.
• Systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment). Patients with possible fungal infections must have had at least 2 weeks of appropriate anti-fungal antibiotics and be asymptomatic.
• Pregnant or lactating. The agents used in this study are known to be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. All females of childbearing potential must have a blood test or urine study within 7 days prior to registration to rule out pregnancy.
• Known allergy to any chemotherapies or targeted agents included in this protocol.
• Participating in a concomitant Phase 1 or 2 study involving treatment of disease.
• Active malignancy other than B-ALL.

Sponsors & Collaborators

• Medical College of Wisconsin: lead
• Amgen: collaborator
• University of Wisconsin, Madison: collaborator

Study Sites (1)

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

MeSH Terms

Conditions

Burkitt Lymphoma

Interventions

blinatumomab

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Rachel Phelan, MD, MPH

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Meredith Beversdorf, RN

CONTACT

414-266-5891; mbeversdorf@chw.org

Emily Ruszkiewicz, BS

CONTACT

414-266-4092; eruszkiewicz@mcw.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Department of Pediatrics, Division of Hematology/Oncology/BMT

Study Record Dates

• First Submitted: September 9, 2020
• First Posted: February 9, 2021
• Study Start: February 1, 2021
• Primary Completion: February 28, 2024
• Study Completion (Estimated): December 31, 2029
• Last Updated: September 17, 2021

Record last verified: 2021-09

Locations

US (1)