Multicenter, single-group, open-label study of T-cell-replete haploidentical stem cell transplantation for relapsed and refractory childhood acute leukemia with low dose anti-thymocyte immunoglobulin

JRCT ID: jRCTs041190061

Registered date:13/08/2019

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Acute leukemia
• Date of first enrollment: 04/10/2019
• Target sample size: 38
• Study type: Interventional
• Intervention(s): After conditioning, haploidentical stem cell transplantation and prevention of GVHD using ATG (before transplant) + TAC + MTX + PSL are performed.

Outcome(s)

• Primary Outcome: 2 year event-free survival

Secondary Outcome

- Cumulative incidence of acute GVHD severity (Overall, II - IV, III - IV)
- 2 year cumulative incidence of chronic GVHD
- Primary survival rate
- 2 year cumulative non relapse mortality rate
- 1 year and 2 years overall survival rate
- Adverse event occurrence rate
- Complete remission rate at 30 days transplantation of non-remission cases at transplant
- Recurrence rate
- 2 year EFS of acute mylogenous leukemia with induction failure
- Long-term toxicity for 1 year and 2 years after transplantation
- Incidence of survival syndrome as of 30th after transplant
- Incidence of complications and infections 100 days after transplantation
- Evaluation on Biomarker for Immune Response after Transplantation
- Association with transplant donor cell composition and outcome
- Evaluation on HLA deletion (escape phenomenon) in recurrent leukemia cells
- Evaluation on prediction of acute GVHD by MLR-ELISPOT method
- Establishment of tumor-bearing animal model with childhood relapsed/refractory leukemia

Key inclusion & exclusion criteria

• Age minimum: >=
• Age maximum: < 20age old
• Gender: Both

Include criteria

(1) Childhood Acute Leukemia Patient at the Time of Initial Age 0 to under 18 and under the age of 20 when registering
(2) It is a relapsed / refractory case having one of the following stages
(2-1) non-remission for the first two or more different induction therapies
(2-2) extremely early and early relapsed ALL (corresponding to BFM recurrence risk classification S3, 4) within 6 months after treatment, during treatment,
(2-3) Recurrence AML less than 1 year after treatment start
(2-4) Relapse after transplantation (including autologous, syngeneic, allogeneic transplantation, haploidentical transplantation)
(2-5) Second recurrence or more
(3) HLA haploidentical transplant donors are present
(4) ECOG Performance status (PS) 0 - 3
(5) Patients enrolled for JPLSG's forward vision study (JPLSG-CHM-14)
(6) Patients who agreed in writing (including ascent) from the principal and / or substitute for this study participation

Exclude criteria

(1) Relapsed leukemia patients with extramedullary invasion only (eg central nervous invasion only)
(2) Ph1 positive acute leukemia patients who have never received treatment with tyrosine kinase inhibitor (TKI)
(3) There is a merger of congenital chromosomal abnormality syndrome such as Down's syndrome
(4) There is an organ failure that interferes with examination treatment
(4-1) Renal function: serum creatinine value is less than twice as high as the age-specific upper limit
(4-2) cardiac function: heart failure requiring treatment and arrhythmia. Or less than 50% EF or less than 28% SF
(4-3) Liver function: AST / ALT is at least 5 times higher than age-specific reference value upper limit (CTCAE grade 3 or more) and T-Bil is at least 3 times higher than age-specific reference value upper limit (CTCAE grade 3 or more)
(4-4) Respiratory function: There is a breathing disorder that is less than 95% SpO 2 in room air or requires oxygen administration
(5) Patients who have an uncontrolled infection (including active tuberculosis, HIV infection)
(6) Patients who are pregnant or possibility of pregnancy
(7) Have congenital or psychiatric disorders that interfere with study treatment
(8) Secondary cancers other than recurrent hematopoietic tumors are merged
(9) Patients received two or more myeloablative conditioning allogeneic transplantation in the past
(10) Secondary leukemia
(11) myeloid NK cell leukemia
(12) There is a history of hypersensitivity in drugs used for pretransplant treatment and prevention of acute GVHD
(13) Any inappropriate status judged by physician

Related Information

• Primary Sponsor: Sano Hideki
• Source(s) of Monetary Support: KANEKA CORPORATOIN,Japan Agency for Medical Research and Development,The Japanese Society of Hematology,Japan Society for the Promotion of Science,Reconstruction Agency,Gold Ribbon Network