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

Study Overview
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Brief Summary
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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).

Detailed Description
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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).

Official Title
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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

Conditions
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Allogeneic Hematopoietic Cell Transplantation

Intervention / Treatment
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* Drug: TCRαβ+/CD19+ depleted allogeneic hematopoietic stem cell transplant (HSCT)


Participation Criteria
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Eligibility Criteria
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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.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TCRαβ+/CD19+ depleted HSCT<br> | Drug: TCRαβ+/CD19+ depleted allogeneic hematopoietic stem cell transplant (HSCT)<br>* 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.<br>|

What is the study measuring?
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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 |