NCT03655145

HLA 10/10 Matched Unrelated Donor vs Haploidentical Allogenic Hematopoietic Stem Cell Transplantation

Randomized Prospective Phase III Clinical Trial Comparing HLA 10/10 Matched Unrelated Donor and Haploidentical Allogenic Hematopoietic Stem Cell Transplantation After Myeloablative Conditioning Regimen

• Status: Unknown
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 344 (estimated)
• Sponsor: Assistance Publique - Hôpitaux de Paris · Academic / Other
• Sex: All
• Age: 15 Years – 55 Years
• Healthy volunteers: Not accepted

Summary

The MAC-HAPLO-MUD trial is a randomized prospective phase III trial comparing HLA 10/10 matched unrelated donor and haploidentical allogeneic hematopoietic stem cell transplantation after myeloablative conditioning regimen in patients, age 15 years or older, with Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL) or Myeloproliferative Syndrome (SMP) or Myelodysplastic Syndromes (SMD) and requiring allogeneic hematopoietic stem cell transplantation. Primary endpoint is the 1-year progression free survival without acute grade II-IV GvHD and without moderate and severe chronic GvHD.

Detailed description

An unrelated adult donor who is HLA-matched to the recipient at the allele-level (at HLA-A, -B, -C, -DQB1 and -DRB1) is considered the best choice in the absence of an HLA-matched sibling for patients needing hematopoietic stem cell transplantation (SCT). However, using matched unrelated donors (MUD) is limited by (1) a prolonged time to identify and schedule donation for some MUD allowing some patients to relapse before transplantation can be performed, and (2) limited availability of fully HLA-MUD for the non-Caucasian population. Alternative donors are used for transplantation in patients without a fully-MUD including single HLA mismatched unrelated donor, unrelated umbilical cord blood and grafts from haploidentical related donors but are associated with higher non-relapse mortality and delayed immune reconstitution. A more recent strategy for haploidentical (haplo) related donor SCT (haplo-SCT) has improved dramatically outcomes using T-cell replete grafts with administration of post-transplantation cyclophosphamide (PTCy). From retrospective studies, haplo-SCT with PTCy are associated with similar overall and progression-free survivals as with MUD stem cell transplantation (MUD-SCT), but with lower rates of toxicity and graft versus host disease (GvHD), and thus potentially better results than MUD-SCT after reduced intensity conditioning (RIC) regimen. Haplo-SCT with PTCy is thus highly discussed nowadays motivating prospective trials to confirm the benefit of this procedure. In the setting of a myeloablative conditioning (MAC) regimen in adults with high risk hematological malignancies, few retrospective non-controlled registry studies recently suggest that outcomes after haplo-SCT using PTCy approach might also be superior in terms of GVHD free survival to that after MUD stem cell transplantation (MUD-SCT). The investigators propose to address this question, in a randomized prospective phase III clinical trial comparing HLA 10/10 MUD and haplo-SCT after MAC regimen. The stem cell source will be bone marrow for haploidentical SCT and peripheral blood stem cell (PBSC) for HLA-matched unrelated transplantation. The primary endpoint is the 1-year progression free survival without acute grade II-IV GvHD and without moderate and severe chronic GvHD.

Conditions

• Acute Myeloid Leukemia
• Acute Lymphoblastic Leukemia
• Myeloproliferative Syndromes
• Myelodysplastic Syndromes

Interventions

Type	Name	Description
OTHER	Haplo donor stem cell transplantation	The algorithm for selection of haploidentical donor has been defined by the french society for stem cell transplantation The stem cell source will be bone marrow for haploidentical transplantation.The bone marrow collection is carried out according to the practice of each centre with a minimal target dose of 3x108 TNC/kg.
OTHER	HLA 10/10 MUD stem cell transplantation	HLA 10/10 matched unrelated donor myeloablative transplantation

Timeline

• Start date: 2018-08-01
• Primary completion: 2019-06-01
• Completion: 2023-06-01
• First posted: 2018-08-31
• Last updated: 2018-08-31