Alpha/Beta T-cell and B-cell Depleted Allogeneic Transplantation (IDE 13641) Followed by Blinatumomab Therapy for High-Risk B-Acute Lymphoblastic Leukemia: A Pilot Study

Who is this study for? Patients with high-risk B-acute lymphoblastic leukemia
What treatments are being studied? Alpha/Beta T-cell and B-cell depleted HCT+Blinatumomab
Status: Recruiting
Location: See location...
Intervention Type: Device, Drug
Study Type: Interventional
Study Phase: Phase 2
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.

Eligibility
Participation Requirements
Sex: All
Maximum Age: 25
Healthy Volunteers: f
View:

• 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

Locations
United States
Wisconsin
Children's Hospital of Wisconsin
RECRUITING
Milwaukee
Contact Information
Primary
Meredith Beversdorf, RN
mbeversdorf@chw.org
414-266-5891
Backup
Emily Ruszkiewicz, BS
eruszkiewicz@mcw.edu
414-266-4092
Time Frame
Start Date: 2021-02-01
Estimated Completion Date: 2029-12-31
Participants
Target number of participants: 25
Treatments
Experimental: Alpha/beta T-cell and B-cell Depleted, Myeloablative HCT
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.
Experimental: Alpha/beta T-cell and B-cell Depleted, Reduced Intensity HCT
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.
Sponsors
Collaborators: Amgen, University of Wisconsin, Madison
Leads: Medical College of Wisconsin

This content was sourced from clinicaltrials.gov

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