TCDαβ/CD45RA Haploidentical Transplantation in Children With Leukemia

Not Applicable

Recruiting

• Conditions: Acute Graft-Versus-Host Disease (Gvhd) Grade IV (Diagnosis); Relapsed Pediatric AML; Relapsed Pediatric ALL
• Interventions: Procedure: In Vitro T cells depletion using CliniMCAS system

• Registration Number: NCT04033627
• Lead Sponsor: Shanghai Children's Medical Center

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2019-06-12
• Study First Submitted QC: 2019-07-23
• Study First Posted: 2019-07-26
• Study Start: 2020-11-10
• Primary Completion: 2022-07-18
• Status Verified: 2022-09
• Last Update Submitted: 2022-09-28
• Last Update Posted: 2022-09-29
• Study Completion: 2024-05-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
In Vitro T cell depletion	In Vitro T cells depletion using CliniMCAS system	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Shanghai Children's Medical Center; 🇨🇳 Shanghai, China