TCDαβ/CD45RA Haploidentical Transplantation in Children With Leukemia

Study Overview
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Brief Summary
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This is a multi-center clinical study in China using CliniMACS TCRα/β+ and CD45RA+ T cell depleted stem cell grafts from haploidentical donors for hematopoietic stem cell transplantation in children.

Detailed Description
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This clinical study will the CliniMACS TCRα/β and CD45RA Systems to deplete TCRα/β+ and CD45RA+ cells from the mobilized peripheral blood stem cells of a haploidentical donors to treat pediatric patients who were suffuring form relapsed or refactory leukemia. Aming to evaluate the safety/tolerability and feasibility of haploidentical PBSC grafts depleted of TCRα/β+ and CD45RA+ cells using the CliniMACS TCRαβ/CD45RA System in pediatric patients with hematological malignancies diseases. And the incidence of grade II-IV acute graft-versus-host disease (GVHD) until Day 100 post-transplantation of this new In Vitro T cell depletion technology in China. The investigators will monitor the incidence of grade I acute GVHD until Day 100 post-transplantation, incidence and severity of chronic GVHD after 1 year and 2 years, incidence of NRM at all visits throughout the study, and graft failure from Day 0 to Day 28 at the same time.

Official Title
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A Multi-center Prospective Clinical Study in China Using CliniMACS TCRα/β+ and CD45RA+ T Cell Depleted Stem Cell Grafts From Haploidentical Donors for Hematopoietic Stem Cell Transplantation in Children With Leukemia

Conditions
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Relapsed Pediatric ALL, Acute Graft-Versus-Host Disease (Gvhd) Grade IV (Diagnosis), Relapsed Pediatric AML

Intervention / Treatment
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* Procedure: In Vitro T cells depletion using CliniMCAS system


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pediatric patients with hematological malignancies in complete remission (CR), partial remission (PR) or with stable disease Acute myeloid leukemia (AML): Patients with high-risk AML in CR1 Patients with relapsed or primary therapy-refractory AML Acute lymphoid leukemia (ALL): Patients with high-risk ALL in CR1 Patients with relapsed or primary refractory ALL Exclusion Criteria: Age >18 years or <8 weeks Patients with progressive disease prior HCT <3 months after preceding hematopoietic cell transplantation (HCT) History of neurological impairment (active seizures, severe peripheral neuropathy, signs of leukencephalopathy, active CNS infection) Fungal infections with radiological and clinical progression Liver function abnormalities with bilirubin >2 mg/dL and elevation of transaminases higher than 400 U/L Chronic active viral hepatitis Ejection fraction <40% or shortening fraction <25% on echocardiography Patients with > grade II hypertension by Common Toxicity Criteria (CTC) Creatinine clearance below threshold defined for stem cell transplantation according to local clinical standard Respiratory failure necessitating supplemental oxygen HIV infection Concurrent severe or uncontrolled medical disease (e.g. uncontrolled diabetes, congestive heart failure, myocardial infarction within 6 months prior to the study, unstable and uncontrolled hypertension, chronic renal disease, or active uncontrolled infection) which by assessment of the treating physician could compromise participation in the study Patients with a history of psychiatric illness or a condition which could interfere with their ability to understand the requirements of the study (this includes alcoholism/drug addiction) Patients unwilling or unable to comply with the protocol or unable to give informed consent Treatment with any investigational product within 4 weeks prior to study treatment (transfusion of the IMP)

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 18 Years

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: In Vitro T cell depletion<br>Use the CliniMACS TCRα/β and CD45 Systems to deplete TCRα/β+ and CD45RA+ cells from the mobilized peripheral blood stem cells of a haploidentical donor in patients with leukemia. | Procedure: In Vitro T cells depletion using CliniMCAS system<br>* Use the CliniMACS TCRα/β and CD45 Systems to deplete TCRα/β+ and CD45RA+ cells from the mobilized peripheral blood stem cells of a haploidentical donor in patients with leukemia.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Log number of In Vitro T cells depletion | Log number of In Vitro T cells depletion using CliniMACS TCRab/CD45RA system. | One week | 
| Incidence of grade II-IV acute GVHD | Incidence of grade II-IV acute graft-versus-host disease (GVHD) until Day 100 post-transplantation. | up to 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Grade I aGVHD | Incidence of grade I acute GVHD until Day 100 post-transplantation | up to 3 months | 
| cGVHD | Incidence and severity of chronic GVHD in 1 year and 2 years | 2 years | 
| NRM | Incidence of NRM at all visits throughout the study | 1 year | 
| Graft failure | incidence of Graft failure from Day 0 to Day 28 | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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In Vitro T cell depletion, haploidentical transplantation, GVHD, leukemia, TCRab, CD45RA, CliniMACS