The Optimization of Haploidentical Hematopoietic Stem Cell Transplantation

NCT ID: NCT05629260

Last Updated: 2023-09-11

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 300 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-12-01
• Study Completion Date: 2025-12-31

Brief Summary

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.

Conditions

Hematological Malignancy

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

ATG

Intervention Type: DRUG

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.

Post-transplantation cyclophosphamide

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: collaborator

Peking University People's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Xiao-Jun Huang

Prof.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

People's Hospital of Peking University

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xu Zhengli, M.D

Role: CONTACT

xuzhengli0202@163.com

86-10-88326904

Xiao-Jun Huang, M.D

Role: CONTACT

Facility Contacts

Zhengli Xu, M.D

Role: primary

xuzhengli0202@163.com

Xiao-Jun Huang, M.D

Role: backup

Other Identifiers

GM-2021-13560

Identifier Type: -

Identifier Source: org_study_id