TCRαβ+/CD19+ Depleted Allogeneic Hematopoietic Stem Cell Transplantation for Malignant and Non-malignant Disorders

Safety and Efficacy of TCRαβ+/CD19+ Depleted Allogeneic Hematopoietic Stem Cell Transplantation for Malignant and Non-malignant Disorders in Children and Adolescent/Young Adult Patients

The purpose of this study is to investigate the safety and efficacy of TCRαβ+/CD19+ depleted allogeneic hematopoietic stem cell transplant (HSCT) for malignant and non-malignant disorders in children and adolescent/young adult patients using the CliniMACS® immunomagnetic selection device (Miltenyi Biotec).

Study Overview

• Status: Terminated
• Conditions: Allogeneic Hematopoietic Cell Transplantation
• Intervention / Treatment: Drug: TCRαβ+/CD19+ depleted allogeneic hematopoietic stem cell transplant (HSCT)

Detailed Description

Acute graft versus host disease (GVHD) remains a significant cause of morbidity and mortality and is the biggest barrier to successful allogeneic hematopoietic cell transplantation (HSCT) outcomes. Improved methods of acute GVHD prevention are needed. TCRαβ+/CD19+ depletion of allogeneic hematopoietic stem cell products offers an opportunity to limit the risk of acute GVHD by removing TCRαβ+ T cells and CD19+ B cells which participate in acute GVHD initiation and perpetuation. The purpose of this study is to investigate the safety and efficacy of TCRαβ+/CD19+ depleted allogeneic hematopoietic stem cell transplant (HSCT) for malignant and non-malignant disorders in children and adolescent/young adult patients using the CliniMACS® immunomagnetic selection device (Miltenyi Biotec).

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Celeste Dourson; Phone Number: 513-636-7679; Email: Celeste.Dourson@cchmc.org

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Any patient being treated at Cincinnati Children's Hospital requiring an allogeneic HSCT who lacks an HLA-genotypically matched related donor. Genotypically matched related donors are allowed when there is a clinical desire to avoid the use of GVHD prophylaxis medications.

Exclusion Criteria:

• Prior allogeneic transplant with active acute or chronic GVHD, or life-threatening infection. Patients with a prior history of allogenic transplant without active GVHD or life-threatening infection can be considered.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: TCRαβ+/CD19+ depleted HSCT

Drug: TCRαβ+/CD19+ depleted allogeneic hematopoietic stem cell transplant (HSCT); The majority of TCRαβ+ T cells and CD19+ B cells will be removed from the allogeneic graft utilizing the CliniMACS® immunomagnetic selection device (Miltenyi Biotec). The depletion process involves two phases; cell labeling (phase 1) and the automated immunomagnetic depletion process (phase 2). The CD34+ dose may be adjusted by the need to not exceed the TCRαβ+CD3+ dose threshold.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Infusion-related Reactions	Number of patients who experienced infusion reactions including rash, fever, difficulty breathing, and blood pressure abnormalities at the time of infusion of stem cells.	100 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Engraftment and Sustained Donor Chimerism	Initial neutrophil engraftment prior to day +28 was determined by monitoring for neutrophil count recovery post-transplant and performing blood tests to confirm presence of donor cells. Sustained donor chimerism at 1 year post transplant was determined again by performing blood tests to confirm presence of donor cells.	28 days and 1 year
Number of Participants With Acute GVHD	Patients were monitored for symptoms of acute graft versus host disease including rash, diarrhea, and increased bilirubin using the Modified Glucksberg Criteria.	100 days
Number of Participants With Chronic GVHD	Patients were monitored for symptoms of chronic graft versus host disease using the NIH Consensus Criteria.	1 year
GVHD-free Survival	GVHD-free survival was determined based on the presence or not of acute or chronic GVHD at 1 year.	1 year

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2019
• Primary Completion (Actual): May 14, 2021
• Study Completion (Actual): September 3, 2021

Study Registration Dates

• First Submitted: September 12, 2019
• First Submitted That Met QC Criteria: September 12, 2019
• First Posted (Actual): September 13, 2019

Study Record Updates

• Last Update Posted (Actual): September 8, 2023
• Last Update Submitted That Met QC Criteria: August 16, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 2018-8568

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No