Higher-dose UM171 to improve cord blood stem cell transplants

Single-site, Prospective, Open-label Phase I-II Study on Transplantation Using Cord Blood Treated With an Optimized Dose of UM171: Optimized ECT-001-CB.

This will try a higher lab dose of UM171 to expand umbilical cord blood stem cells for adults with high-risk leukemia or myelodysplasia who lack a suitable donor to see if they recover blood counts faster and have fewer complications after transplant.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 7 (estimated)
• Ages: 18 Years to 67 Years
• Sex: All
• Sponsor: Ciusss de L'Est de l'Île de Montréal (other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Montreal, Quebec)
• Trial ID: NCT07301866 on ClinicalTrials.gov

What this trial studies

This single-center, open-label Phase I/II trial enrolls seven adults with high-risk acute leukemia or myelodysplasia who lack a suitable donor and uses ex vivo expansion of cord blood units with UM171 at an optimized higher dose (125 nM versus the conventional 35 nM) in a dose-escalation design. The expanded product, ECT-001-CB, will be infused as an allogeneic hematopoietic stem cell transplant and patients will be followed for one year. Primary endpoints include safety, feasibility, and time to neutrophil engraftment, with secondary endpoints such as immune recovery, infection rates, hospital stay length, and overall outcomes. The trial builds on earlier UM171 work that improved engraftment and immune reconstitution and now tests whether a higher concentration can further increase long-term repopulating cells and balanced lymphoid/myeloid recovery.

Who should consider this trial

Good fit: Adults 18–67 with high-risk acute leukemia or myelodysplasia (or another hematologic malignancy requiring allogeneic HSCT) who lack a suitable adult donor and have an available cord blood unit meeting HLA and cell-dose requirements are ideal candidates.

Not a fit: Patients who have a matched adult donor, whose cord blood units do not meet HLA or cell-dose criteria, or who fall outside the age/comorbidity limits are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, this approach could speed blood count recovery, reduce infections and hospital time, and lower transplant-related mortality for patients without a matched donor.

How similar studies have performed: Earlier trials of UM171-expanded cord blood units reported faster engraftment, improved immune reconstitution, and lower non-relapse mortality, but the higher 125 nM dose in this trial is a new, unproven escalation.

Eligibility criteria

Inclusion Criteria:

1. Subjects ≥ 18 and ≤ 67 years old,
2. Patient with either i. High risk acute leukemia or myelodysplasia defined as expected 2 year OS or PFS \< 40% after a conventional allogeneic HSC transplant or ii. A hematologic malignancy requiring an allogeneic hematopoietic stem cell transplant and lack of a suitable HLA identical, haploidentical or 7/8 HLA matched donor.
3. Availability of an adequate CB for expansion:

   i. ≥ 5/8 HLA match when A, B, C and DRB1 are performed at the allele level.

   ii. Minimal cell dose: TNC ≥ 1.5 x 107/kg, and CD34 ≥ 0.5 x 105/kg. iii. Needs to be erythrodepleted by bank prior to cryopreservation. iv. Must comply with local site regulations AND, come from a cord bank that is FACT, or AABB accredited, or FDA approved or eligible for NMDP IND (unless PI approves another bank).

   v. To meet eligibility criteria, the patient's weight at time of cord selection will be used; however, if this weight has increased by more than 5% at time of admission to hospital and with the new weight the patient no longer meets eligibility criteria for cell dose, LI approval will be required to move forward with the selected cord. Every attempt will be made to always use the most recent weight in cord selection
4. Patients with adequate physical function as measured by:

   i. Karnofsky score ≥ 70% ii. Hematopoietic comorbidity index (HCT-CI): 0-3 for 2nd transplant and age 60-65 years, 0-5 if \<60 years old, and 0-2 if 66-67 years.

   iii. Adequate cardiac function: Left ventricular ejection fraction ≥ 40% within 60 days prior to start of conditioning regimen iv. Adequate pulmonary function: Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and diffusing capacity corrected for hemoglobin (DLCOc) ≥ 50% of predicted within 60 days prior to start of conditioning regimen.

   v. Adequate hepatic function: Bilirubin \< 2 x ULN unless felt to be related to Gilbert's disease or hemolysis; AST and ALT ≤ 2.5 x ULN (the PI may approve up to 3 times ULN) ; alkaline phosphatase ≤ 5 x ULN.

   vi. Adequate renal function: Estimated or measured creatinine clearance ≥ 60 ml/min/1.73m2.
5. A back up graft must have been identified prior to initiation of conditioning regimen.
6. Signed written informed consent.
7. Female patients of childbearing potential must have a negative serum pregnancy test within 30 days of enrolment and within 30 days of starting of preparative regimen; patient must be willing to use an effective contraceptive method while enrolled in the study.

Exclusion Criteria:

1. Allogeneic or autologous myeloablative transplant within last 6 months.
2. Patients with inadequate physical function as measured by:

   i. Active, uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of either progression of clinical symptoms or radiologic findings or lack of evidence of response to therapy).

   ii. Presence of a malignancy other than the one for which the HSC transplant is being performed, with an expected survival estimated to be less than 75% at 5 years.

   iii. Seropositivity for HIV. iv. Hepatitis B or C infection with measurable viral load. Patients with hepatitis B or C infection regardless of viral load require clear documentation of absence of cirrhosis by either fibroscan or biopsy.

   v. Liver cirrhosis.
3. Positive anti-donor HLA antibodies with MFI above 1500 against the selected CB (PI may approve an MFI up to 5000; if above 2500, desensitization is strongly recommended)
4. Use of an investigational agent within 30 days (defined as a drug not approved by Health Canada or FDA regardless of indication) of start of chemotherapy unless documented approval obtained from Sponsor.
5. Presence of ≥30% blasts in bone marrow or ≥ 0.5 x109/L blasts in circulating blood
6. Active central nervous system involvement or chloroma \> 2 cm.

Where this trial is running

Montreal, Quebec

• Hôpital Maisonneuve-Rosemont — Montreal, Quebec, Canada (RECRUITING)

Study contacts

• Principal investigator: Sandra Cohen, Dr. — CIUSSS de l'Est-de-l'Ile-de-Montréal
• Study coordinator: Sandra Cohen, Dr.

Conditions: Acute Leukemia, High Risk, Myelodysplastic Syndromes, High Risk, Hematologic Malignancy Requiring an Allogeneic Hematopoietic Stem Cell Transplant Lacking a Donor, High risk hematologic malignancy, Cord blood transplant, UM171, ECT-001-CB, Lack of donor for stem cell transplant donor