ATG Plus Low-dose PT-Cy for GVHD Prevention

Randomized Trial of Anti-thymocyte Globulin Plus Low-dose Post-transplant Cyclophosphamide for GVHD Prevention in Haploidentical Donor HCT

During the past decades, the wider application of easily available haploidentical donor hematopoietic cell transplant (haplo-HCT) has been made possible through the T cell-replete (TCR) regimens including T cell regulation with anti-thymocyte globulin (ATG)/granulocyte colony-stimulating factor (GCSF) and post-transplant cyclophosphamide (PTCy). To achieve decreased non-relapse mortality (NRM) and improved long-term outcomes in haploidentical transplant, the joint use of ATG and PTCy might effectively reduce graft versus host disease (GVHD) and mortality associated with severe forms of GVHD. Recently, investigators established a regimen using low-dose PTCy in conjunction with standard-dose ATG in order to lower the risk of GVHD without compromising engraftment and disease relapse.

Study Overview

• Status: Recruiting
• Conditions: Hematologic Malignancy
• Intervention / Treatment: Drug: Cyclophosphamid; Drug: ATG

• Study Type: Interventional
• Enrollment (Estimated): 196
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yu Wang, M.D.; Phone Number: 86-13552647384; Email: ywyw3172@sina.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Peking University People's Hospital
    • Contact: Yu Wang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with acute leukemia and/or myelodysplastic syndrome undergoing their first allogeneic hematopoietic stem cell transplantation;
2. Male or female , aged 12-55 years;
3. Haploidentical donor transplantation;
4. ECOG score ≤3; The basic organ function tests met the following standards;

1) Cardiac ejection index >55% 2) Creatinine ≤1.5 times the highest normal value (ULN)

Exclusion Criteria:

1. Severe brain, heart, kidney or liver dysfunction;
2. Refractory malignant state;
3. Patients with other malignant tumors requiring treatment;
4. Clinically uncontrolled severe active infection;
5. The expected survival time was less than 3 months.
6. A history of severe anaphylaxis.
7. Pregnant or lactating women;
8. Any condition considered by the investigators to be unsuitable for enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ATG-PTCy cohort; The conditioning regimen is ATG/G-CSF based protocol (the so-called Beijing protocol). The rabbit ATG (Sangstat-Genzyme) 2.5mg/kg/day i.v., on days from - 5 to - 2 were administered.Two doses of 14.5 mg/kg Cy were given on days 3 and 4 post-HCT in ATG-PTCy cohort.	Drug: Cyclophosphamid; A total of 10mg/kg ATG was administered, and two doses of 14.5 mg/kg Cy were given on days 3 and 4 post-HCT in ATG-PTCy cohort.; Drug: ATG; A total of 10mg/kg ATG was administered.
Active Comparator: ATG cohort; The conditioning regimen is ATG/G-CSF based protocol (the so-called Beijing protocol). The rabbit ATG (Sangstat-Genzyme) 2.5mg/kg/day i.v., on days from - 5 to - 2 were administered.	Drug: ATG; A total of 10mg/kg ATG was administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of acute graft versus host disease.	The incidence of acute graft versus host disease. The severity of acute GVHD was evaluated according to standard international criteria.	100 days post HSCT.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Engraftment	Myeloid engraftment was defined as the first of three consecutive days with an ANC X0.5≥10^9/L.	30 days post HSCT.
The incidence of chronic GvHD	The incidence of chronic GvHD.	1 year post HSCT.
The incidence of non-relapse mortality	The incidence of non-relapse mortality	1 year post HSCT.
The incidence of infection	The incidence of infection	1 year post HSCT.
The incidence of relapse	The incidence of relapse	1 year post HSCT.
Overall survival	Overall survival	1 year post HSCT.
Disease free survival	Disease free survival	1 year post HSCT.
GvHD relapse free survival	GvHD relapse free survival	1 year post HSCT.
Immune reconstitution	Immune reconstitution was evaluated at 1, 2, 3, 6, 9 and 12 months by analysis of peripheral blood MNCs detecting CD3, CD4, CD19 and immunoglobulin (Ig) A, G and M levels.	1 year post HSCT.

Collaborators and Investigators

• Sponsor: Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2023
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: October 22, 2023
• First Submitted That Met QC Criteria: October 29, 2023
• First Posted (Actual): October 31, 2023

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Hematologic Diseases; Hematologic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide
• Other Study ID Numbers: ATG plus PT-Cy in haplo-SCT

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No