Clinical trial · Interventional

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

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

NCT06238245CI-TRIAL-00074124unknownPhase 2ClinicalTrials.gov clinicaltrialsPublishedExplore in graph →

Summary

Brief summary (as posted)

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.

Conditions

Conditions (2)

Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.

Condition (as posted)	Mapped entity	Match	Confidence
Graft-versus-host Disease	—	UNRESOLVED	—
Hematological Malignancies	Hematopoietic and Lymphoid Cell Neoplasm	ALIAS	0.90

Interventions

Interventions (1)

Intervention	Type	Mapped drug	Match
Cyclophosphamid	Drug	—	UNRESOLVED

Design

Arms and outcomes

Arms (1)

type
EXPERIMENTAL
label
Combination of PTCy and ATG for GVHD prophylaxis
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.
interventionNames
1. Drug: Cyclophosphamid

Primary outcomes (1)

measure
acute graft-versus-host disease
timeFrame
100 days
description
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 outcomes (7)

Eligibility

Eligibility (as posted)

Sex: All
Minimum age: 18 Years

Show eligibility criteria text

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.

References

Publications (2)

BACKGROUNDWang 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. PMID 37706580
BACKGROUNDGao 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. PMID 37166484