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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Comparative Study of Haploidentical Transplantation Supported by Third-party Cord Blood and Haploidentical Transplantation in Hematological Malignancies

Conditions
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Hematological Malignancies, Hematopoietic Stem Cell Transplantation

Intervention / Treatment
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* Other: PBSCs
* Other: Cord
* Other: BMSCs


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Haplo-PBSC+Cord group<br>The third party UCB will be infused the day after infusion of PBSCs from HID. | Other: PBSCs<br>* 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.<br>Other: Cord<br>* 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.<br>|
| Active Comparator: Haplo-PBSC+BM group<br>The BMSCs from the same HID will be infused the day after infusion of PBSCs. | Other: PBSCs<br>* 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.<br>Other: BMSCs<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival (DFS) |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse rate |  | 1 year | 
| Overall survival (OS) |  | 1 year | 
| The cumulative incidence of hematopoietic engraftment. | Hematopoietic engraftment includes the time of neutrophil and platelet engraftment. Neutrophil engraftment was defined as the first of two consecutive days with an absolute neutrophil count in the peripheral blood exceeding 0.5 × 10^9/L and the platelet engraftment was defined as the first of 3 days with an absolute platelet count exceeding 20 × 10^9 /L without transfusion support. | 30 days post-transplantation | 
| The cumulative incidence of acute graft-versus-host-disease (GVHD) | Acutue GVHD was defined according to the 1994 consensus conference on acute GVHD grading and graded from I to IV. | 100 days post-transplantation | 
| The cumulative incidence of chronic GVHD | Chronic GVHD was graded as mild, moderate and severe according to the national institutes of health consensus development project on criteria for clinical trials in chronic GVHD: the 2014 diagnosis and staging working group report. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hematological malignancies, Haploidentical transplantation, Umbilical cord blood, Disease-free survival