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

Beijing 302 Hospital

Status and phase: Not yet enrolling; Phase 2

Conditions: Hematological Malignancies; Graft-versus-host Disease

Treatments: Drug: Cyclophosphamid

Study type: Interventional

Funder types: Other

Identifiers

NCT06238245

ATGPTCY-PD1&GVHD2023V1.0

Details and patient eligibility

About

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.

Full 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.

Enrollment: 22 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

22 participants in 1 patient group

Combination of PTCy and ATG for GVHD prophylaxis

Experimental group

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 (two doses of 14.5 mg/kg Cy was given on days +3 and +4 post-HSCT) was used of GVHD prophylaxis.

Treatment:

Drug: Cyclophosphamid