Alpha/Beta T-cell Depleted Blood-forming Stem Cell Transplant From Related or Unrelated Donors for Blood Diseases in Children and Young Adults

NCT04806347 | Not Yet Recruiting Phase 1 DMC FDA Device

• 5 other identifiers: 2020-1251A536755Protocol Version 6NCI-2021-02128UW19113
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is being done to see if the investigators can take peripheral blood stem cells from either an adult family member or a closely matched unrelated donor, and run them through a special lab instrument to remove alpha/beta T cells and B cells and then give them to the patient to treat disease. This is an experimental way of doing a hematopoietic stem cell transplant (HSCT). The investigators want to see if the new stem cells will grow without bad graft vs. host disease (GVHD). This treatment approach is experimental in the United States.

Conditions

Blood Disease

Outcome Measures

Primary Outcomes (4)

• Incidence of grade III-IV acute graft-versus-host disease (GVHD)

  Acute GVHD will be assessed and graded according to the Keystone Consensus Criteria for staging and grading of acute graft-versus-host disease.

  100 days post transplantation

• Incidence of extensive chronic GVHD

  Chronic GVHD will be assessed according to the current CIBMTR (Center for International Blood and Marrow Transplant Research) manual reflecting a grading system published by Sullivan KM (Sullivan 1981).

  up to 2 years

• Incidence of graft failure

  Graft failure - defined as failure to achieve ANC \> 500 /µL at Day +28 or initial neutrophil engraftment followed by a decline in ANC \< 500 /µL that is unresponsive to growth factor therapy (secondary graft failure).

  up to 2 years after graft

• Incidence of Treatment Related Mortality (TRM)

  TRM - defined as death from any cause other than disease progression.

  Day +100 post-HSCT

Secondary Outcomes (15)

• Time to neutrophil engraftment

  up to 28 days following HSCT

• Time to platelet engraftment

  up to 28 days following HSCT

• Percentage donor chimerism using Short Tandem Repeat (STR)

  up to 12 months following HSCT

• Kinetics of lymphocyte reconstitution via immunophenotyping using flow cytometry

  up to 12 months following HSCT

• CliniMACS system efficiency: Percentage of viable CD34+ cells recovered after the TCRαβ+ and CD19+ depletion procedure

  up to 12 months following HSCT

Study Arms (1)

Treatment arm

EXPERIMENTAL

Participants will undergo a conditioning regimen, specific for the original disease, After that peripheral blood stem cell transplant from a haploidentical donor or closely matched unrelated donor, depleted of TCRαβ+ and CD19+ cells using the CliniMACS TCR α/β-biotin and CD19 Systems will be administered intravenously on Day 0 to all participants.

Biological: TCRαβ+/CD19+ depleted Hematopoietic stem cell (HSC) graft; Device: CliniMACS® System

Interventions

CliniMACS® System DEVICE

The CliniMACS Cell Selection System is based on magnetic-activated cell sorting mechanism. The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures.

Treatment arm

TCRαβ+/CD19+ depleted Hematopoietic stem cell (HSC) graft BIOLOGICAL

After undergoing a disease specific conditioning regimen (standard of care), participants will receive peripheral blood stem cell transplant from a haploidentical donor or closely matched unrelated donor, depleted of TCR αβ+ and CD19+ cells using the CliniMACS TCR α/β-biotin and CD19 Systems.

Treatment arm

Eligibility Criteria

• Age: 3 Months - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• No Human leukocyte antigen (HLA) identical sibling available AND
• NO HLA matched unrelated donor available OR urgent need of HSCT precludes time necessary to search for suitable HLA matched unrelated donor AND
• Haploidentical donor OR closely matched unrelated donor available and willing to undergo mobilization and apheresis
• If subject has genetically confirmed inherited bone marrow failure, related donor must be evaluated for this disorder and testing must be negative.
• If subject has sickle cell disease, donor must be unaffected or have only sickle cell trait
• Patient must be diagnosed with one of the following diseases or disorders:
• Hemoglobinopathies
• Sickle Cell Disease for patients ≤ 21 years of age for whom hydroxyurea has been trialed for at least six months, and failed
• Thalassemia Major for patients ≤ 21 years of age
• Acquired Bone Marrow Failure Syndromes
• Paroxysmal Nocturnal Hemoglobinuria with bone marrow failure
• Myelodysplastic Syndromes (lower risk)
• Severe acquired aplastic anemia
• Inherited Bone Marrow Failure Syndromes
• Fanconi Anemia

You may not qualify if:

• Pregnant
• HIV infection
• Uncontrolled, serious active infection at screening
• Significant serious intercurrent illnesses
• Enrollment in any other treatment study that would interfere with the endpoints of this study according to judgement of Principal Investigator (or PI designee).

Sponsors & Collaborators

• University of Wisconsin, Madison: lead

MeSH Terms

Conditions

Hematologic Diseases

Interventions

Transplantation

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Surgical Procedures, Operative

Study Officials

• Christian Capitini, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

• Jacques Galipeau, MD

  University of Wisconsin, Madison

  STUDY DIRECTOR

Central Study Contacts

Jenny Weiland

CONTACT

608-890-8070; PedsHemOncResearch@lists.wisc.edu

Celeste Matsushima

CONTACT

608-890-8069

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2021
• First Posted: March 19, 2021
• Study Start: August 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2030
• Last Updated: July 23, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP