The Optimization of Haploidentical Hematopoietic Stem Cell Transplantation

A Multi-center, Prospective Study of Clinical Outcome and Immune Reconstruction in G-CSF/ATG and PT-Cy Based Haploidentical Transplantation

The goal of this observational study is to compare the incidence of relapse in G-CSF/ATG based and PT-Cy based haploidentical transplantation] in [patients aged 18 to 55 years with a diagnosis of hematological malignancies who unmanipulated haplo-HSCT with myeloablative conditioning]. The main question it aims to answer are:

Primary objective: To compare the incidence of relapse in G-CSF/ATG based and PT-Cy based haploidentical transplantation and illustrate the possible immune mechanism.

Secondary objectives: To compare CMV infection, GVHD and survival outcomes, and to observe the dynamic immune reconstitution of G-CSF/ATG based or PT-Cy based model.

Exploratory objectives: To compare the long-term quality of life among recipients who receive G-CSF/ATG based or PT-Cy based protocol.

Study Overview

• Status: Recruiting
• Conditions: Hematological Malignancy
• Intervention / Treatment: Drug: ATG; Drug: Post-transplantation cyclophosphamide

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Xu Zhengli, M.D; Phone Number: 86-10-88326904; Email: xuzhengli0202@163.com
• Study Contact Backup: Name: Xiao-Jun Huang, M.D

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Recruiting
      • People's Hospital of Peking University
      • Contact: Xiao-Jun Huang, M.D
      • Contact: Zhengli Xu, M.D; Email: xuzhengli0202@163.com
      • Principal Investigator: Xiao-Jun Huang, M.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with hematologic malignancy who are indicated for allogeneic hematopoietic stem cell transplantation (allo-HSCT) and absence of HLA matched donors will be treated with haplo-HSCT with either G-CSF/ATG based or PT-Cy based protocols（4:1）

Description

Inclusion Criteria:

1. Subjects diagnosed as acute leukemia with transplant indications in ≤ CR2;
2. Lack of available, HLA-identical, related sibling or unrelated donor;
3. Female or male, age: 18-55 years old;
4. ECOG performance status 0-2;

5. Adequate organ function as defined by the following criteria:

   Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤2.5× upper limit of normal (ULN), or AST and ALT ≤5× ULN if liver function abnormalities are due to underlying malignancy Total serum bilirubin≤1.5× ULN Serum creatinine≤2.5× ULN

6. Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrollment;
7. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclusion Criteria:

1. Uncontrollable active infection;
2. Severe organic impairment: hepatic and renal impairment;
3. Any of the following within 6 months prior to starting study treatment: myocardial infarction, severe/unstable angina, congestive heart failure, or cerebrovascular accident including transient ischemic attack;
4. Pregnancy or breastfeeding;
5. Psychiatric disorders;
6. Don't sign the informed consent;
7. Prior/concurrent clinical study experience;

8. Other conditions:

   • Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures
   • Participants are employees of the clinical study site or other individuals directly involved in the conduct of the study, or immediate family members of such individuals (in conjunction with section 1.61 of the ICH-GCP Ordinance E6)
   • Any specific situation during study implementation/course that may rise ethics considerations
   • Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
G-CSF/ATG group; Patients in the G-CSF/ATG group received a modified Bu/Cy plus ATG conditioning regimen as follows: cytarabine (4/g m2 per day IV.) on days -10 to -9; Bu (3.2 mg/kg per day IV.) on days -8 to -6; Cy (1.8 g/m2 per day IV.) on days -5 to -4; methyl chloride hexamethylene urea nitrate (Me-CCNU) (250 mg/m2 per day orally) once on day -3; and ATG (2.5 mg/kg per day IV; rabbit, Sang Stat, Lyon, France) on days -5 to -2.	Drug: ATG; Patients with intermediate-high risk hematologic malignancy who are indicated for allogeneic hematopoietic stem cell transplantation (allo-HSCT) and absence of HLA matched donors will be treated with haplo-HSCT, with G-CSF/ATG based protocol.
PT-Cy group; Patients in PT-Cy group received a Bu/Flu/Cy-based conditioning regimen as follows: Flu (40 mg/m2 or 1 mg/kg IV) on days -8 to -4; Bu (3.2 mg kg/ d-1 IV) on days -7 to -4; Cy (14.5-40 mg/kg IV) on days -3 to -2;±cytarabine (3 g/m2/d IV) on days -9 to -8; and ± IDA (15 mg/m2/d IV) on days -9 to -8. The addition of IDA and/or cytarabine depended on the performance status of the patients and whether the patients were in relapse status. High-dose PTCy (50 mg/kg/d IV) was administered on days +3 and +4.	Drug: Post-transplantation cyclophosphamide; Patients with intermediate-high risk hematologic malignancy who are indicated for allogeneic hematopoietic stem cell transplantation (allo-HSCT) and absence of HLA matched donors will be treated with haplo-HSCT with PT-Cy based protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of participants with disease relapse	The cumulative incidence of relapse of the primary disease.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of CMV disease	The cumulative incidences of CMV disease in participants after transplantation	6 months
Cumulative incidences of aGVHD	The diagnosis and grading of aGVHD are based on the modified Glucksberg grading standard.	100 days
Cumulative incidences of cGVHD	Chronic GVHD can be classified as "limited" or "extensive" according to the Seattle criteria, and also be classified as "mild" or "moderate" or "severe" according to the National Institutes of Health (NIH) criteria.	1 year
Percent of participants with overall survival	Overall survival (OS) is defined as the time from randomization to death resulting from any cause.	1 year
Dynamic immune reconstitution	The main immune cell subsets include: T cell, B cell, NK cell, and Monocytes	1 year
Neutrophil engraftment	Neutrophil engraftment is defined as the first of 3 consecutive days with an absolute neutrophil count > 0.5 × 10^9/L.	1 month
Platelet engraftment	Platelet engraftment is defined as the first of 7 consecutive days with an absolute platelet count > 20 × 10^9/L independent from transfusion	1 month
Transplantation-related mortality	Death due to causes unrelated to the underlying disease	1 year

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Collaborators: Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2022
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: November 17, 2022
• First Submitted That Met QC Criteria: November 28, 2022
• First Posted (Actual): November 29, 2022

Study Record Updates

• Last Update Posted (Actual): September 11, 2023
• Last Update Submitted That Met QC Criteria: September 8, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Haploidentical Transplantation; G-CSF/ATG; PT-Cy
• 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: GM-2021-13560

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No