Haplo-PBSC+Cord vs Haplo-PBSC+BM for Hematological Malignancies Undergoing Allo-HSCT

NCT ID: NCT05290545

Last Updated: 2024-08-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 314 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-15
• Study Completion Date: 2024-03-30

Brief Summary

The objective of this study was to explore whether the combination with umbilical cord blood (UCB) is associated with superior disease-free survival (DFS) in the setting of haploidentical donors (HID) transplantation.

Detailed Description

The main causes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) failure are primary disease relapse and transplant-related complications, especially relapse. In recent years, with the development of transplantation technology, alternative donors such as HID and UCB have been widely used. But, these alternative donors are associated with high incidences of transplant-related complications and mortalities when compared with human leukocyte antigen (HLA)-matched donors. Some studies suggeted that mixed grafts might overcome the disadvantages of a single alternative graft. UCB transplant (UCBT) supported by third-party HID or HID transplants supported by third-party UCB has been reported to have rapid engraftment and low incidences of graft-versus-host-disease (GVHD), making survival improvement. However, most of these results came from single-arm studies. The comparative studies between haplo-PBSC+Cord and haplo-PBSC+BM are scarce in the setting of HID transplantation. In a retrospective study, the investigators found haplo-PBSC+Cord transplantation has superior DFS than haplo-PBSC+BM in hematological malignancies. To further confirmed this conclusion, the investigators plan to conduct a prospective, multicenter, phase 3 randomized controlled trial.

Conditions

Hematological Malignancies; Hematopoietic Stem Cell Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Haplo-PBSC+Cord group

The third party UCB will be infused the day after infusion of PBSCs from HID.

Group Type: EXPERIMENTAL

PBSCs

Intervention Type: OTHER

PBSCs harvest is performed from day 5 of G-CSF to obtain at least 7.0×10\^8 total nucleated cells/kg recipient ideal body weight.

Cord

Intervention Type: OTHER

The criteria for cord selection included the following: (1) ≥3 of 6 HLA loci , (2) blood type matches, (3) contained a minimum cell count of 0.3×10\^8 nucleated cells/kg and 0.15×10\^6 CD34-positive cells/kg before freezing. The third party UCB will be infused the day after infusion of PBSCs.

Haplo-PBSC+BM group

The BMSCs from the same HID will be infused the day after infusion of PBSCs.

Group Type: ACTIVE_COMPARATOR

PBSCs

Intervention Type: OTHER

PBSCs harvest is performed from day 5 of G-CSF to obtain at least 7.0×10\^8 total nucleated cells/kg recipient ideal body weight.

BMSCs

Intervention Type: OTHER

BMSCs of donor will be collected and infused at least 0.5×10\^8 total nucleated cells/kg recipient ideal body weight the day after PBSCs infusion.

Interventions

PBSCs

PBSCs harvest is performed from day 5 of G-CSF to obtain at least 7.0×10\^8 total nucleated cells/kg recipient ideal body weight.

Intervention Type: OTHER

Cord

The criteria for cord selection included the following: (1) ≥3 of 6 HLA loci , (2) blood type matches, (3) contained a minimum cell count of 0.3×10\^8 nucleated cells/kg and 0.15×10\^6 CD34-positive cells/kg before freezing. The third party UCB will be infused the day after infusion of PBSCs.

Intervention Type: OTHER

BMSCs

BMSCs of donor will be collected and infused at least 0.5×10\^8 total nucleated cells/kg recipient ideal body weight the day after PBSCs infusion.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Patients with hematologic malignancies undergoing first HID allo-HSCT
• Age 18 to 65 years old with ECOG performance status 0-2
• Received myeloablative conditioning regimens
• Sign informed consent form, have the ability to comply with study and follow-up procedures

Exclusion Criteria

• Received PBSCs as only grafts
• Acute leukemia transformed from a myeloproliferative tumor
• Cardiac dysfunction (particularly congestive heart failure, unstable coronary artery disease and serious cardiac ventricular arrhythmias requiring antiarrhythmic therapy)
• Respiratory failure ( PaO2 ≤60mmHg)
• Hepatic abnormalities (total bilirubin ≥3 mg/dL, aminotransferase >2 times the upper limit of normal)
• Renal dysfunction (creatinine clearance rate < 30 mL/min)
• ECOG performance status 3, 4 or 5
• With any conditions not suitable for the trial (investigators' decision)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

First Affiliated Hospital of Guangxi Medical University

OTHER

Sponsor Role: collaborator

Hunan Provincial People's Hospital

OTHER

Sponsor Role: collaborator

The Seventh Affiliated Hospital of Sun Yat-sen University

OTHER

Sponsor Role: collaborator

First People's Hospital of Chenzhou

OTHER

Sponsor Role: collaborator

Dongguan People's Hospital

OTHER_GOV

Sponsor Role: collaborator

The First People's Hospital of Guangzhou

UNKNOWN

Sponsor Role: collaborator

Nanfang Hospital, Southern Medical University

OTHER

Sponsor Role: lead

Responsible Party

Liu Qifa

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Qifa Liu

Role: PRINCIPAL_INVESTIGATOR

Nanfang Hospital, Southern Medical University

Locations

Department of Hematology,Nanfang Hospital, Southern Medical University

Guangzhou, Guangdong, China

Countries

China

References

Yu S, Huang F, Xu N, Zhang Z, Liu C, Xu X, Fan Z, Zeng X, Liu Q, Qiu G, Xi X, Lin R, Liang X, Jiang Y, Dai M, Jin H, Li X, Wang S, Wu M, Sun J, Xuan L, Liu Q. Haploidentical peripheral blood stem cells combined with bone marrow or unrelated cord blood as grafts for haematological malignancies: an open-label, multicentre, randomised, phase 3 trial. Lancet Haematol. 2025 Mar;12(3):e190-e200. doi: 10.1016/S2352-3026(24)00372-7. Epub 2025 Feb 4.

Reference Type: DERIVED

PMID: 39919775 (View on PubMed)

Other Identifiers

NFEC-2021-126

Identifier Type: -

Identifier Source: org_study_id