NCT03913026

UM171 Expanded Cord Blood In Patients With High-Risk Acute Leukemia/Myelodysplasia

A Phase II Open-label Study of ECT-001-expanded Cord Blood Transplantation in Patients With High-risk Acute Leukemia/Myelodysplasia

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Ciusss de L'Est de l'Île de Montréal · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

Allogeneic hematopoietic stem cell transplantation is a life-saving procedure in patients with blood cancers. Cord blood (CB) represents an alternative source of stem cells, which is associated with a lower risk of relapse, especially in the presence of minimal residual disease in the setting of acute leukemia and myelodysplasia. Furthermore, CB has the added advantage of being associated with a low risk of chronic graft versus host disease (GVHD). Unfortunately, CB transplants are hampered by a higher risk of transplant related mortality (TRM) when compared to bone marrow/peripheral blood transplants because of the limited cell dose of CB. In the previous UM171 trial (NCT02668315), the CB expansion protocol using the ECT-001-CB technology (UM171 molecule) has proven to be technically feasible and safe. UM171 expanded CB was associated with a median neutrophil recovery at day (D)+18 post transplant. Amongst 22 patients who received a single UM171 CB transplant with a median follow-up of 18 months, risk of TRM (5%) and grade 3-4 acute GVHD (10%) were low. There was no moderate-severe chronic GVHD. Thus, overall and progression free survival at 12 months were impressive at 90% and 74%, respectively. The UM171 expansion protocol allowed access to smaller, better HLA matched CBs as \>80% of patients received a 6-7/8 HLA matched CB. Interestingly there were 5 patients who had already failed an allogeneic transplant and 5 patients with refractory/relapsed acute leukemia/aggressive lymphoma. Despite this high risk population, progression was 20% at 12 months. Hence, in this new trial, investigators are targeting patients with high and very high-risk acute leukemia/myelodysplasia to test the antileukemia effect of this new graft, a UM171 expanded CB.

Detailed description

Methodology: This is a multi-center open label phase II clinical trial. Patients with high and very high-risk acute leukemia/myelodysplasia will receive a single 5-7/8 HLA matched ECT-001 (UM171) expanded cord blood after an ablative conditioning regimen. This group of patients would be expected to have poor progression free survival (PFS) after a conventional allogeneic transplant (bone marrow-peripheral blood). Investigators key primary and secondary objectives include: 1. To confirm low Transplant Related Mortality (TRM) 2. To evaluate relapse free survival (RFS) 3. To analyze kinetics of hematologic engraftment; 4. To evaluate the incidence of acute and chronic GVHD 5. To evaluate the safety of the procedure 6. To evaluate incidence of infectious complications 7. To analyze duration of hospitalization 8. To evaluate the incidence of pre-engraftment/engraftment syndrome (PES/ES) 9. To analyze the effect of cryopreservation of the expanded CD34+ fraction on safety and efficacy endpoints

Conditions

• High Risk Hematologic Malignancy
• Cord Blood Transplant

Interventions

Type	Name	Description
BIOLOGICAL	Transplant with an expanded ECT-001 cord blood	1. Patients will receive a conditioning regimen (such as: cyclophosphamide 120 mg/kg, fludarabine 75mg/m2 and TBI 12 Gy or cyclophosphamide 50 mg/kg, fludarabine 150 mg/m2, thiotepa 10 mg/kg and TBI 4 Gy). 2. The cord to be expanded will undergo CD34+ selection. The CD34- product is cryopreserved and will be thawed and infused on Day +1 post-transplant. The CD34+ product will be placed in a closed culture with UM171 for a 7-day expansion and is infused on Day 0. 3. Patients will receive standard supportive care and GVHD prophylaxis (such as MMF and tacrolimus). Tacrolimus will be discontinued on Day 100 post-transplant unless GVHD arises.

Timeline

• Start date: 2019-04-01
• Primary completion: 2027-06-01
• Completion: 2027-06-01
• First posted: 2019-04-12
• Last updated: 2025-10-27

Locations

1 site across 1 country: Canada

Regulatory

• FDA-regulated drug study