Haploidentical Hematopoietic Stem Cell Transplantation With Ex Vivo TCR Alpha/Beta and CD19 Depletion in Pediatric Hematologic Malignancies

NCT05011422 | Recruiting Phase 1 DMC FDA Device

• 1 other identifier: 202203051
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This single arm pilot phase I study with safety run-in is designed to estimate the safety and efficacy of a familial mismatched or haploidentical hematopoietic stem cell transplantation (haplo-HSCT) using a novel graft modification technique (selective αβ-TCR and CD19 depletion).

Conditions

Pediatric Hematologic Malignancies

Outcome Measures

Primary Outcomes (4)

• Safety as measured by the number of events occurring within the first 100 days post-transplant

  -Events are death, disease recurrence or progression, and graft failure

  Through 100 days post-transplant

• Engraftment as measured by time to neutrophil count recovery

  Time to neutrophil recovery is defined as the first of 3 measurements on different days when the patient has an absolute neutrophil count of \>500/μL after conditioning.

  From day of transplant (day 0) to 42 days (+/- 14 days) post transplant

• Engraftment as measured by time to platelet count recovery

  Time to platelet recovery is defined as the first day of a minimum of 3 measurements on different days that the patient has achieved a platelet count \> 50,000/μL AND did not receive a platelet transfusion in the previous 7 days. The exception is the case in which a patient receives platelet transfusions specifically to achieve a higher platelet threshold to allow for an invasive procedure or protection if determined to be at elevated bleeding risk.

  From day of transplant (day 0) to 75 days (+/- 14 days) post transplant)

• Donor cell chimerism as measured by short tandem repeat analysis

  * Can use peripheral blood samples or bone marrow samples * The percent of donor-derived cells are sequentially followed.

  Through day +100

Secondary Outcomes (23)

• Event free survival (EFS)

  At 24 months post transplant

• Overall survival (OS)

  At 24 months post transplant

• Incidence of grade IV acute GVHD

  Weekly through day +100

• Incidence of severe chronic GVHD

  Day 101 through 24 months

• Change in Lansky/Karnofsky performance score

  Day +100, Day +180, Day +365, and +24 months

Study Arms (2)

Recipients: ex vivo αβ-TCR/CD19 depleted haplo-hematopoietic stem cell infusion (HSCT)

EXPERIMENTAL

* Patients will undergo standard of care conditioning regiment prior to HSCT * On Day 0, patients will undergo infusion of the ex vivo αβ-TCR/CD19 depleted haplo-HSCT from a stimulated peripheral stem cell source per institutional standard of care. Patients whose graft has a residual CD20+ count \> 1.0 x 10\^5 may receive a single infusion of rituximab on Day +1 at a dose of 375 mg/m\^2 at provider's discretion.

Device: Ex Vivo T-cell receptor alpha-beta and CD19+ Depletion using CliniMACs Plus

Donors:

NO INTERVENTION

Donors who meet the eligibility criteria will be mobilized as per institutional standard practice using G-CSF 10 mcg/kg/day with leukapheresis to take place on Day 5. The target volume for collection is 20 L. Up to 4 days of pheresis are permitted to ensure target collection.

Interventions

Ex Vivo T-cell receptor alpha-beta and CD19+ Depletion using CliniMACs Plus DEVICE

Once pheresed, the product will be washed to remove platelets and the cell concentration will be adjusted per laboratory and ClinicMACS technology recommendations. It is then labeled using the CliniMACS αβ-TCR Biotin Kit and CD19+ immunomagnetic microbeads. After labeling, the cells are washed to remove unbound microbeads. The partially processed product is loaded on the CliniMACS device where labeled cells are depleted and the negative fraction is eluted off the device. The negative fraction is centrifuged and volume reconstituted to obtain the final product

Recipients: ex vivo αβ-TCR/CD19 depleted haplo-hematopoietic stem cell infusion (HSCT)

Eligibility Criteria

• Age: Up to 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Must meet at least one of the following disease criteria:
• B cell ALL in first remission and any of the following:
• Persistent flow-based MRD at end-of-consolidation:
• ≥ 1% for NCI SR ALL
• ≥ 0.01% for NCI HR ALL
• TCF3-HLF t(17;19)
• KMT2A rearranged infant ALL, \< 6 months of age and presenting WBC of \> 300,000 or poor steroid response (peripheral blasts \>= 1000 /uL on day 8 of therapy
• Other high-risk features not explicitly stated here, after discussion/approval with protocol PI.
• B cell ALL in second remission and any of the following:
• Early (\<36 months from start of therapy) marrow or combined relapse
• Late (\>36 months from start of therapy) marrow or combined relapse with end-of re-induction flow MRD \>= 0.1%
• Early isolated extramedullary relapse (\< 18 months from start of therapy)
• Any B cell ALL in third or greater remission
• T cell ALL in first remission
• End-of consolidation MRD \> 0.1%

You may not qualify if:

• Available matched related donor. A patient with a matched unrelated donor is eligible if urgent transplantation is required. A prior unrelated donor search is not required for enrollment.
• Active non-hematologic malignancy. History of other malignancy is acceptable as long as therapy has been complete and there is no evidence of disease.
• Currently receiving any other investigational agents at the time of transplant.
• Active CNS or extramedullary disease. History of CNS or extramedullary disease now in remission is acceptable.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to conditioning agents used in the study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (bacterial, viral with clinical instability, or fungal), symptomatic congestive heart failure, or unstable cardiac arrhythmia.
• Presence of significant anti-donor HLA antibodies per institutional standards. Anti-donor HLA Antibody Testing is defined as a positive crossmatch test of any titer (by complement dependent cytotoxicity or flow cytometric testing) or the mean fluorescence intensity (MFI) of any anti-donor HLA antibody by solid phase immunoassay.
• Presence of a second major disorder deemed a contraindication for HSCT.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of the start of conditioning.
• Donor Eligibility Criteria:
• At least 6 months of age
• Meets the selection criteria as defined by the Foundation for the Accreditation of Hematopoietic Cell Therapy (FACT).
• Able to understand and willing to sign an IRB-approved written informed consent document (or that of legally authorized representative, if applicable).

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study Officials

• Thomas Pfeiffer, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Thomas Pfeiffer, M.D.

CONTACT

314-273-2070; pthomas@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2021
• First Posted: August 18, 2021
• Study Start: November 3, 2022
• Primary Completion (Estimated): May 31, 2029
• Study Completion (Estimated): May 31, 2029
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)