Reduced versus standard dose post-transplant cyclophosphamide with tacrolimus and a single low-dose ATG to prevent GVHD after alternative-donor peripheral stem cell transplant

A Multi-center Randomized Clinical Study Comparing Reduced-dose (35mg/kg) Versus Standard Dose (50mg/kg) Post-transplantation Cyclophosphamide in Combination With Post-engraftment Anti-thymoglobin (ATG) and Tacrolimus and Post-engraftment Anti-thymoglobin as Graft Versus Host Disease (GVHD) Prophylaxis in Patients Undergo Alternative Donor Peripheral Hematopoietic Stem Cell Transplantation

This trial will see if a lower dose (35 mg/kg) of post-transplant cyclophosphamide plus tacrolimus and one low dose of ATG prevents graft-versus-host disease as well as the standard 50 mg/kg dose in patients receiving an allogeneic peripheral stem cell transplant from an unrelated or haploidentical donor.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 316 (estimated)
• Ages: 18 Years to 55 Years
• Sex: All
• Sponsor: Shanghai Jiao Tong University School of Medicine (Academic / other)
• Drugs / interventions: cyclophosphamide
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06705062 on ClinicalTrials.gov

What this trial studies

This is a randomized, phase 3, multicenter trial comparing reduced-dose post-transplantation cyclophosphamide (35 mg/kg on days +3 and +4) versus the standard dose (50 mg/kg on days +3 and +4) for graft-versus-host disease (GVHD) prophylaxis after alternative-donor peripheral stem cell transplantation. Both groups receive tacrolimus starting on day +5 and a single post-engraftment low dose of anti-thymocyte globulin (2.5 mg/kg). Eligible participants are patients receiving allo-HSCT from 9-10/10 matched unrelated or haploidentical donors who meet organ function and performance-status criteria. The trial is designed to compare feasibility and clinical outcomes related to GVHD prevention and post-transplant recovery between the two dosing strategies.

Who should consider this trial

Good fit: Ideal candidates are patients undergoing allogeneic peripheral stem cell transplantation from a matched unrelated (9-10/10) or haploidentical donor who meet the trial's organ function (renal, hepatic, pulmonary, cardiac) and performance-status (ECOG 0-2) requirements and can provide informed consent.

Not a fit: Patients who are pregnant, have active hepatitis with high viral load, active infections requiring antibiotics, HIV infection, or inadequate organ function are excluded and therefore unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the reduced PTCy dose could lower drug-related toxicity while maintaining protection against GVHD, potentially improving recovery after alternative-donor allo-HSCT.

How similar studies have performed: Post-transplant cyclophosphamide is an established GVHD prevention strategy and lower-dose approaches have been explored in smaller or nonrandomized studies, but large randomized phase 3 comparisons are limited.

Eligibility criteria

Inclusion Criteria:

1. patients undergo allo-HSCT with matched unrelated donor or haplo-identical donor;
2. normal organ function (creatinine clearance ≥ 50ml/min/1.73m2 or creatinine ≤2mg/d(or 177μmol/L); no hepatic abnormal (ALT or AST≤2.5xN; TBil≤1.5XN); Normal pulmonary function (FEV1、 FVC、DLCO≥80%); normal cardiac function (EFS ≥50%);
3. ECOG: 0-2;
4. Life expectation ≥3 months;
5. Informed consent provided.

Exclusion Criteria:

1. Pregnancies
2. active hepatitis (HBV-DNA≥1×103 copies/ml);
3. active infection require anti-biotics;
4. HIV infection

Where this trial is running

Shanghai, Shanghai Municipality

• Ruijin hsopital — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: Jiong HU — Ruijin Hospital
• Study coordinator: Jiong HU

Conditions Allogeneic Hematopoietic Cell Transplant; Graft Versus Host Disease; post-transplantation cyclophosphamide; prophylaxis; reduced dose; graft versus host disease