TCDαβ/CD45RA Haploidentical Transplantation in Children With Leukemia

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

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.

Study Overview

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

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 Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: luo chengjuan; Phone Number: 82030 +86 021 38626161; Email: luochengjuan@scmc.com.cn

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Shanghai Children's Medical Center
    • Contact: Jing Chen; Phone Number: 18930830632; Email: chenjing@scmc.com.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 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: In Vitro T cell depletion; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shanghai Children's Medical Center
• Collaborators: Chinese University of Hong Kong; Nanfang Hospital of Southern Medical University; Miltenyi Biomedicine GmbH; Children's Hospital of Soochow University
• Investigators: Principal Investigator: Jing Chen, Shanghai Children's Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2020
• Primary Completion (Actual): July 18, 2022
• Study Completion (Anticipated): May 8, 2024

Study Registration Dates

• First Submitted: June 12, 2019
• First Submitted That Met QC Criteria: July 23, 2019
• First Posted (Actual): July 26, 2019

Study Record Updates

• Last Update Posted (Actual): September 29, 2022
• Last Update Submitted That Met QC Criteria: September 28, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: GVHD; leukemia; In Vitro T cell depletion; haploidentical transplantation; TCRab; CD45RA; CliniMACS
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Leukemia; Graft vs Host Disease
• Other Study ID Numbers: TCD Haplo

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