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

NCT03913026 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: ECT-001-CB.002
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

High Risk Hematologic Malignancy; Cord Blood Transplant

Keywords

UM171; Stem Cell Expansion

Outcome Measures

Primary Outcomes (3)

• Transplant Related Mortality (TRM)

  TRM is defined as any death of any cause other than malignant relapse, occurring after the commencement of conditioning regimen that could be related to the transplantation procedure.

  1 year

• Relapse Free survival (RFS)

  RFS will be measured from time of transplant until disease relapse, death or last follow-up.

  2 years

• Overall survival (OS)

  OS will be measured from time of transplant until disease relapse, death or last follow-up.

  2 years

Secondary Outcomes (9)

• Neutrophil Engraftment

  42 days

• Graft failure

  42 days

• Platelet Engraftment

  60 days

• Incidence of Acute Graft Versus Host Disease (aGVHD)

  1 year

• Incidence of Chronic Graft Versus Host Disease (cGVHD)

  2 years

Other Outcomes (3)

• Immune reconstitution

  1 year

• Identify markers suggesting escape from the immune system

  3 years

• Graft composition and evaluation

  7 days

Study Arms (1)

Main intervention

EXPERIMENTAL

Eligible patients will receive an ablative conditioning regimen and be infused with an ECT-001 expanded cord-blood. The ECT-001 expanded CB could be infused fresh, or cryopreserved.

Biological: Transplant with an expanded ECT-001 cord blood

Interventions

Transplant with an expanded ECT-001 cord blood BIOLOGICAL

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.

Main intervention

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Presence of high-risk acute leukemia/myelodysplasia defined as one of the following:
• I. Acute Myeloid Leukemia:
• Primary induction failure (no CR or CRi after ≥ 2 courses of induction therapy or after ≥ 1 induction containing high dose Ara-C)
• Chemorefractory relapse (no CR or CRi after 1 chemointensive treatment)
• Relapse after allogeneic or autologous transplant
• High risk AML in CR1: i) any adverse genetic abnormality as defined by European Leukemia Net excluding FLT3 mutation; ii) secondary or therapy related AML excluding good risk genetic abnormalities (as defined by ELN); or iii) any other poor risk feature known to be associated with a PFS or DFS ≤40% at 2 years after conventional transplantation.
• CR2 excluding good risk genetic abnormalities defined by ELN
• ≥CR3
• II. Acute Lymphoid Leukemia
• Primary induction failure (≥ 2 inductions)
• Chemorefractory relapse (at least 1 intensive induction chemotherapy; blinatumomab, inotuzumab or CAR-T cells may be considered as an equivalent)
• Relapse after allogeneic or autologous transplant
• High risk ALL in CR1: Ph like ALL or any other poor risk feature known to be associated with an PFS or DFS ≤40% at 2 years after conventional transplantation.
• ≥CR2
• MRD+ within 1 month of start of conditioning regimen.

You may not qualify if:

• Patient never treated with cytotoxic chemotherapy and planned conditioning regimen does not include 12 Gy TBI (exceptions allowed if approved by PI).
• Allogeneic myeloablative transplant within 6 months.
• Autologous hematopoietic stem cell transplant within 6 months.
• Planned use of ATG in conditioning regimen (exceptions allowed if approved by PI in which case ATG must be adjusted for weight/lymphocyte count and given more than 1 week prior to transplant; any patient who receives ATG will have immune recovery studies but will not be counted with rest of patients and will be analyzed separately).
• Planned use of an HLA matched CB (8/8 allele matched)
• Uncontrolled infection.
• Presence of a malignancy other than the one for which the CB transplant is being performed, with an expected survival estimated to be less than 75% at 5 years.
• Seropositivity for HIV.
• Hepatitis B or C infection with measurable viral load. Patients with chronic hepatitis B or C infection regardless of viral load require clear documentation of absence of cirrhosis by either fibroscan or biopsy. If fibroscan is the method used, the test must be unequivocally negative.
• Liver cirrhosis.
• Active central nervous system involvement
• Chloroma \> 2 cm
• ≥50% blasts in marrow in an evaluable marrow sample (\>25% of normal cellularity for age) collected less than one month prior to start of conditioning regimen.
• Peripheral blasts \>1000/mm3
• Pregnancy, breastfeeding or unwillingness to use appropriate contraception.

Sponsors & Collaborators

• Ciusss de L'Est de l'Île de Montréal: lead
• Stem Cell Network: collaborator
• ExCellThera inc.: collaborator

Study Sites (1)

CIUSSS de l'Est-de-l'île-de Montreal, Hôpital Maisonneuve-Rosemont

Montreal, Quebec, H1T2M4, Canada

Location

MeSH Terms

Interventions

Transplantation

Intervention Hierarchy (Ancestors)

Surgical Procedures, Operative

Study Officials

• Sandra Cohen, MD

  Ciusss de L'Est de l'Île de Montréal

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor University of Montreal

Study Record Dates

• First Submitted: April 9, 2019
• First Posted: April 12, 2019
• Study Start: April 1, 2019
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: October 27, 2025

Record last verified: 2025-10

Locations

CA (1)