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

NCT06238245 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: ATGPTCY-PD1&GVHD2023V1.0
• Study Type: interventional
• Target: 22
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Graft-versus-host Disease; Hematological Malignancies

Outcome Measures

Primary Outcomes (1)

• acute graft-versus-host disease

  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.

  100 days

Secondary Outcomes (7)

• chronic graft-versus-host disease

  1-year

• recurrence free survival

  1-year

• non-relapse mortality

  1-year

• cumulative incidence of relapse

  1-year

• overall survival

  1-year

Study Arms (1)

Combination of PTCy and ATG for GVHD prophylaxis

EXPERIMENTAL

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.

Drug: Cyclophosphamid

Interventions

Cyclophosphamid DRUG

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 mismatched 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.

Also known as: Anti-thymocyte globulin

Combination of PTCy and ATG for GVHD prophylaxis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• (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;

You may not qualify if:

• (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.

Sponsors & Collaborators

• Beijing 302 Hospital: lead

Related Publications (2)

• 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.

  PMID: 37706580 BACKGROUND

• 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.

  PMID: 37166484 BACKGROUND

MeSH Terms

Conditions

Graft vs Host Disease; Hematologic Neoplasms

Interventions

Cyclophosphamide; Antilymphocyte Serum

Condition Hierarchy (Ancestors)

Immune System Diseases; Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures

Study Officials

• Xiaoning Gao, Doctor

  Chinese PLA General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiaoning Gao, Doctor

CONTACT

+86-010-66947169; gaoxn@263.net

Yuxin Wang, Doctor

CONTACT

15147159987; wyx15147159987@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2024
• First Posted: February 2, 2024
• Study Start: February 28, 2024
• Primary Completion: December 30, 2025
• Study Completion (Estimated): June 30, 2026
• Last Updated: February 20, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share