Clinical trial NCT04033627: TCDαβ/CD45RA Haploidentical Transplantation in Children With Leukemia
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Relapsed Pediatric ALL
Acute Graft-Versus-Host Disease (Gvhd) Grade IV (Diagnosis)
Relapsed Pediatric AML
Keywords: In Vitro T cell depletion
haploidentical transplantation
GVHD
leukemia
TCRab
CD45RA
CliniMACS
Lead sponsor: Shanghai Children's Medical Center
Sponsor class: OTHER
Collaborators: name: Nanfang Hospital, Southern Medical University
name: Children's Hospital of Soochow University
name: Chinese University of Hong Kong
name: Miltenyi Biomedicine GmbH
First posted: 2019-07-26
Enrollment: 30
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Log number of In Vitro T cells depletion
timeFrame: One week
measure: Incidence of grade II-IV acute GVHD
timeFrame: up to 3 months
Secondary outcomes:
measure: Grade I aGVHD
timeFrame: up to 3 months
measure: cGVHD
timeFrame: 2 years
measure: NRM
timeFrame: 1 year
measure: Graft failure
timeFrame: 1 month
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Children's Medical Center
Study officials:
affiliation: Shanghai Children's Medical Center
name: Jing Chen
role: PRINCIPAL_INVESTIGATOR
References: