Clinical trial for HLA-haploidentical transplantation using alpha-beta T cell and B cell depletion

JRCT ID: jRCTs032230287

Registered date:10/08/2023

Basic Information

• Recruitment status: Recruiting

Health condition(s) or Problem(s) studied

Fanconi anenia
severe combined immunodeficiency

• Date of first enrollment: 16/02/2024
• Target sample size: 3
• Study type: Interventional
• Intervention(s): Pre-transplant conditioning chemo-radiotherapy is administered according to disease. Additional rituximab (375mg/me2) is administered in conditioning on day -1 to reduce the risk of post transplantation lymphoproliferative disorders. After conditioning, peripheral blood stem cell from HLA-haploidentical donor which is alpha-beta-T cells depleted by more than 4 logs and B cells depleted by more than 3 logs using CliniMACS is infused. No post-transplantation immunosuppressive therapy is done for GVHD prophylaxis. However, tacrolimus 0.02mg/kg/day is administered in patients who received more than 1x10e5 alpha-beta-T cells per kilogram.

Outcome(s)

Primary Outcome

graft failure at 30 days after transplantation
death up to 30 days after transplantation

Secondary Outcome

Donor-derived platelet count of 20,000/ul or higher after transplantation
Acute GVHD (grade II or higher) within 100 days after transplantation
Treatment-related mortality within 100 days after transplantation
Transplant-related complications up to 1 year after transplantion
Occurrence of infectious disease within 100 days after transplantation
Reconstitution of lymphocyte function up to 1 year after transplantation
Days from transplantation to onset of chronic GVHD
Days from transplantation to relapse
Days from transplant to death
Days from transplantation to neutrophil engraftment
Development of malignancy after transplantation
PTLD within 100 days after transplantation
Acute reactions to rituximab administration
secondary graft failure
CliniMACS failure
Grade 4 or higher of non-hematologic adverse events

Key inclusion & exclusion criteria

• Age minimum: Not applicable
• Age maximum: < 18age old
• Gender: Both

Include criteria

1)Patients with Fanconi anemia or severe combined immunodeficiency who are difficult to receive allogeneic hematopoietic stem cell transplantation (HSCT) using PTCY.
2)At time of registration, patients who require allogeneic HSCT, but HLA7/8 antigen (A, B, C, DRB1) matched or 8/8 antigen matched donor is not available. Therefore, the intended donor is one of the following.
a. HLA4/8 antigen (A, B, C, DRB1) matched related donor.
b. HLA5/8 antigen (A, B, C, DRB1) matched related donor.
c. HLA6/8 antigen (A, B, C, DRB1) matched related donor.
3)Patients under 18 years of age at the time of HSCT.
4)Patients with an ECOG performance status (PS) score of 0-2 at enrollment.
5)Patients with adequate organ function who meet the following criteria at the time of enrollment. Laboratory findings must be within 30 days prior to enrollment.
a.Serum direct bilirubin <1.5mg/dL
b.Serum creatinine
<5 years old, <0.8mg/dL
5-9 years old, <1.2mg/dL
>10 years old, <1.5mg/dL
c.Ejection fraction>45% and QTc<0.45sec
6)Patients whose written consent from legal representative have been obtained to participate in this study.

Exclude criteria

1) Patients who had received prior HSCT.
2) The donor is unable to use G-CSF due to allergy or other reasons.
3) Patients who have uncontrollable infection.
4) Patients with severe mental disorder.
5) Patients with pregnant or likely to be pregnant.
6) Patients who are ineligible by physician

Related Information

• Primary Sponsor: Iguchi Akihiro
• Source(s) of Monetary Support: National Center for Child Health and Develoment