Reduced ATG Plus Mini PTCy for GVHD Prophylaxis in Haplo-SCT

Phase 2RecruitingNCT06984536

Peking University People's Hospital40 enrolled

Overview

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is regarded as a curative therapy for a variety of hematological malignancies and nonmalignant diseases. However, donor limitations have restricted the widespread use of allo-HSCT for a long period. The development and success of haploidentical allografts worldwide makes "everyone has a donor" a reality. In the past two decades, researchers have established several haploidentical HSCT (haplo-HSCT) protocols based on different approaches to induce immune tolerance. The representative approaches for haplo-HSCT without in vitro. T cell depletion include granulocyte colony-stimulating factor (G-CSF) plus Anti-human Thymocyte Immunoglobulin (ATG) based (Beijing Protocol) and post-transplantation cyclophosphamide based (PT-Cy, Baltimore Protocol) protocols. Both of two protocols have common problems that need to be solved, including infection transplantation related mortality and disease relapse. The main aim of this study is to explore whether the combined protocol can improve the efficacy of haploidentical transplantation further.

Study Type

INTERVENTIONAL

Allocation

Purpose

PREVENTION

Masking

NONE

Enrollment

Conditions

Myelodysplastic Syndrome Acute Leukemia

Interventions

Reduced ATG plus mini PTCyDRUG

The conditioning protocol comprises cytarabine (Ara-C) (4 g/m2/day, days -9), busulfan (Bu) (3.2 mg/kg/day, days -8 to -6), cyclophosphamide (Cy) (1.8 g/m2/kg, days -5 and -4), simustine (250 mg/m2, day -3) and r-ATG (total 7.5mg/kg ,from days -5 to -2). Mini PTCy 14.5mg/kg/day will be given on day +3 and +4.

Eligibility

Sex: ALLMin age: 12 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Patients with AL - CR and/or myelodysplastic syndromes undergoing allogeneic hematopoietic stem cell transplantation for the first time; 2. No gender limit, aged 12 - 65 years; 3. Planned haploidentical donor transplantation, excluding transplantation from maternal and collateral donors; 4. Eastern Cooperative Oncology Group (ECOG) performance status score≤3 points; 5. Baseline organ function tests meet the following criteria: (1) Left ventricular ejection fraction (LVEF) \> 55%; (2) Serum creatinine ≤ 1.5 × upper limit of normal (ULN). Exclusion Criteria: 1. Patients with severe dysfunction of brain, heart, kidney or liver; 2. Those in refractory malignant status; 3. Patients with other malignancies requiring treatment; 4. Presence of uncontrolled severe active infection clinically; 5. Expected survival period of less than 3 months; 6. History of severe allergic reactions; 7. Pregnant or breastfeeding women; (8)Presence of any condition deemed by the investigator as unsuitable for study enrollment.

Outcomes

Primary Outcomes

Non-relapse mortality

None-relapse mortality within 100 days post transplantation

Time frame: 100 days

Secondary Outcomes

Regimen related toxicity

Regimen related toxicity will be evaluated by Bearman Criteria from the begining of conditioning to 1 month post HSCT. The organ functions that need to be assessed include the heart, liver, kidneys, cystitis, oral mucositis, and the gastrointestinal tract.

Time frame: 30 days post transplantation

Engraftment

Myeloid and platelet engraftment

Time frame: Within 30 days post transplant. Myeloid engraftment was deﬁned as the ﬁrst of three consecutive days with an ANC 0.5×109 /L, and platelet engraftment was deﬁned as the day the platelet count met or exceeded 20×10^9 /L without transfusion for a week.

Disease relapse

The incidence of disease relapse

Time frame: 1 year post transplantation

Disease free survival

The time from the start of transplantation until a patient experiences leukemia relapse or death from any cause, whichever occurs first.