Clinical trial NCT06238245: Combination of ATG-based Conditioning Regimen and PTCy for GVHD Prevention in Allo-HSCT After PD-1 Blockade
Official title: A Prospective, Single-Arm Clinical Study of Anti-thymocyte Globulin-based Conditioning Regimen Combined With Post-Transplantation Cyclophosphamide for GVHD Prevention in Allogeneic HSCT After PD-1 Blockade
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Graft-versus-host Disease
Hematological Malignancies
Lead sponsor: Beijing 302 Hospital
Sponsor class: OTHER
First posted: 2024-02-02
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: acute graft-versus-host disease
timeFrame: 100 days
Secondary outcomes:
measure: chronic graft-versus-host disease
timeFrame: 1-year
measure: recurrence free survival
timeFrame: 1-year
measure: non-relapse mortality
timeFrame: 1-year
measure: cumulative incidence of relapse
timeFrame: 1-year
measure: overall survival
timeFrame: 1-year
measure: GVHD-free/ relapse-free survival
timeFrame: 1-year
measure: PD-L1 expression in acute myeloid leukemia bone marrow cells
timeFrame: Up to 1 year post-treatment
Other outcomes:
Locations:
Study officials:
affiliation: Chinese PLA General Hospital
name: Xiaoning Gao, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wang H, Wang N, Wang L, Du J, Li F, Shao Y, Peng B, Luan S, Wang L, Jin X, Gao C, Dou L, Liu D. Targeted dosing of anti-thymocyte globulin in adult unmanipulated haploidentical peripheral blood stem cell transplantation: A single-arm, phase 2 trial. Am J Hematol. 2023 Nov;98(11):1732-1741. doi: 10.1002/ajh.27068. Epub 2023 Sep 14.
citation: Gao XN, Su YF, Li MY, Jing Y, Wang J, Xu L, Zhang LL, Wang A, Wang YZ, Zheng X, Li YF, Liu DH. Single-center phase 2 study of PD-1 inhibitor combined with DNA hypomethylation agent + CAG regimen in patients with relapsed/refractory acute myeloid leukemia. Cancer Immunol Immunother. 2023 Aug;72(8):2769-2782. doi: 10.1007/s00262-023-03454-y. Epub 2023 May 11.