Combination of ATG-based Conditioning Regimen and PTCy for GVHD Prevention in Allo-HSCT After PD-1 Blockade

Phase 2

Not yet recruiting

• Conditions: Graft-versus-host Disease; Hematological Malignancies
• Interventions: Drug: Cyclophosphamid

• Registration Number: NCT06238245
• Lead Sponsor: Beijing 302 Hospital

Brief Summary

The aim of this study is to evaluate the efficacy and safety of anti-thymocyte globulin combined with PTCy (post-HSCT cyclophosphamide, PTCy) in preventing graft-versus-host disease (GVHD) in allo-HSCT patients after anti-PD-1(anti-programmed cell death protein 1) antibody treatment. In this study, patients with hematological malignancies who needed to receive allo-HSCT after PD-1 antibody treatment were selected as the research subjects. Fludarabine and Busulfan was used as the conditioning regimen, and the dose of ATG (anti-thymocyte globulin, ATG) combined with PTCy was used as the GVHD prevention regimen. The aim of this study is to reduce the incidence of Regimen-Related Toxicity and GVHD without affecting engraftment and relapse, thereby reducing non-relapse mortality and further improving the survival of patients.

Detailed Description

ATG (anti-thymocyte globulin, rabbit; 5 mg/kg, day -5 to -2) was used in matched sibling donor-HSCT. ATG (1.5 mg/kg, day -5; 2.5 mg/kg, day -4; mathematical function was then exploited to determine the total targeted ATG dose on day -3 to -2 based on concentrations of active ATG on day -5 to -4) was used in both haploidentical donor-HSCT and unrelated donor-HSCT. Reduced-dose PTCy regimen: two doses of 14.5 mg/kg Cy were given on days +3 and +4 post-HSCT.

Study Timeline

• Status Verified: 2024-01
• Study First Submitted: 2024-01-24
• Study First Submitted QC: 2024-02-01
• Study First Posted: 2024-02-02
• Last Update Submitted: 2024-02-19
• Last Update Posted: 2024-02-20
• Study Start: 2024-02-28
• Primary Completion: 2025-12-30
• Study Completion: 2026-06-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 22

Inclusion Criteria

• (1) age ≥ 18 years old, regardless of gender;
• (2) patients with hematological malignancies (including lymphoma, leukemia, myelodysplastic syndrome, etc.) who had received at least one course of PD-1 antibody treatment;
• (3) patients with indications for allo-HSCT, available donors (including matched sibling donors, haploidentical donors and unrelated donors), and no contraindications for transplantation;
• (4) patients suitable for conventional Bu/Flu conditioning regimen;
• (5) no serious heart, liver, kidney, lung and other important organ diseases;
• (6) Eastern Cooperative Oncology Group (ECOG) performance status score 0-2;
• (7) Hematopoietic stem cell transplantation comorbidity index (HCT-CI) score was 0-3;
• (8) expected survival time of at least 12 weeks;
• (9) women who are not pregnant or breastfeeding;
• (10) voluntary participation in clinical research; They or their legal guardians were fully aware of the study and signed informed consent. Willing to follow and complete all trial procedures;

Exclusion Criteria

• (1) pregnant or lactating women;
• (2) other serious conditions that may limit enrollment (e.g., advanced infection, etc.);
• (3) unable to understand and follow the study protocol or sign the informed consent form.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Combination of PTCy and ATG for GVHD prophylaxis	Cyclophosphamid	ATG (anti-thymocyte globulin, rabbit; 5 mg/kg, day -5 to -2) was used in matched sibling donor-HSCT. ATG (1.5 mg/kg, day -5; 2.5 mg/kg, day -4; mathematical function was then exploited to determine the total targeted ATG dose on day -3 to -2 based on concentrations of active ATG on day -5 to -4) was used in both haploidentical donor-HSCT and unrelated donor-HSCT. Reduced-dose PTCy (two doses of 14.5 mg/kg Cy was given on days +3 and +4 post-HSCT) was used of GVHD prophylaxis.

Primary Outcome Measures

Name	Time	Method
acute graft-versus-host disease	100 days	Acute graft-versus-host disease severity is usually graded (grades 0-IV) by the pattern of organ involvement using the classic Glucksberg-Seattle criteria (GSC). Higher grades mean a worse outcome.

Secondary Outcome Measures

Name	Time	Method
cumulative incidence of relapse	1-year	cumulative incidence of relapse was measured from the date of transplantation until the date of hematologic relapse.
recurrence free survival	1-year	Recurrence Free Survival is defined as the time interval between the day of reference in the study (date of randomization, date of diagnosis, etc.) and the date of local relapse/recurrence or regional relapse/recurrence or death (all causes) whichever occurs first.
non-relapse mortality	1-year	Non-relapse mortality was defined as death from any cause other than malignancy relapse.
overall survival	1-year	The time from transplantation to any cause death or the last follow-up was defined as overall survival.
chronic graft-versus-host disease	1-year	The National Institutes of Health scoring system (National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report) was used to define chronic GVHD. The standardization provided by the National Institutes of Health (NIH) 2005 and 2014 consensus projects has helped improve diagnostic accuracy and severity scoring (including grades mild, moderate, and severe) for clinical trials. Higher scores mean a worse outcome.
GVHD-free/ relapse-free survival	1-year	GVHD-free/ relapse-free survival events were defined as grade 3-4 aGVHD or cGVHD requiring systemic immunosuppressive treatment, disease relapse, or any-cause death during the first 12 months after allogeneic HCT.
PD-L1 expression in acute myeloid leukemia bone marrow cells	Up to 1 year post-treatment	The expression levels of PD-L1 in acute myeloid leukemia bone marrow cells will be assessed at the 28th day after each medication cycle.