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 4NCI-2021-02128UW19113
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

Brief Summary

This single institution, phase I clinical trial will determine the safety and feasibility of employing T-cell receptor (TCR) αβ+ and CD19+ (Cluster of Differentiation ) depleted hematopoietic stem cell transplantation (HSCT) using peripheral blood stem cells (PBMC) from closely matched unrelated donors or haploidentical donors to treat non-malignant hematologic diseases in children and young adults. Allogeneic hematopoietic stem cell transplantation has become a curative option for children and adolescents with a variety of otherwise fatal conditions. To reduce the incidence and severity of graft-versus-host disease (GVHD) associated with allogeneic hematopoietic stem cell transplantation, donor grafts are depleted of T cells, either using CD34+ selection or CD3+/CD19+ depletion of grafts. However, these selection processes also deplete the graft of protective cell subsets, such as γδ T cells, natural killer(NK) cells, monocytes and dendritic cells, which play important roles in the immune response to infectious agents. Moreover, the presence of NK cells and γδ T in donor grafts is associated with more rapid immune reconstitution after HSCT transplantation. In order to retain these protective immune cell subsets, this trial will use a novel, highly selective graft engineering process using the Miltenyi CliniMACS system that selectively depletes αβ-T cells and B cells which are responsible for GVHD and Epstein Barr Virus (EBV)-related post-transplantation lymphoproliferative disorder, respectively. Prior to transplantation, patients will be treated with a conditioning regimen, specific for the original disorder. The primary objective of this study is evaluation of the safety and feasibility of HSCT using TCRαβ+/CD19+ depleted hematopoietic stem cells to treat non-malignant hematologic diseases. This will be assessed by evaluating the incidence of graft failure, grade III-IV acute GVHD and chronic GVHD and TRM. Secondary objectives include the evaluation of immune reconstitution and incidence of post-transplant infections, adverse events, serious adverse events, overall and disease-free survival and the efficiency of graft processing by the CliniMACS System.

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 - 40 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 may 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)
• Inherited Bone Marrow Failure Syndromes
• Fanconi Anemia
• Diamond Blackfan 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: April 1, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2030
• Last Updated: February 10, 2026

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share