US Study of UM171-Expanded CB in Patients With High Risk Leukemia/Myelodysplasia

A Phase II Open-Label Study of UM171-Expanded Cord Blood Transplantation in Patients With High and Very High Risk Acute Leukemia/Myelodysplasia

Cord blood (CB) transplants are an option for patients lacking an HLA identical donor but are hampered by low cell dose, prolonged aplasia and high transplant related mortality. UM171, a novel and potent agonist of hematopoietic stem cell self renewal could solve this major limitation, allowing for CB's important qualities as lower risk of chronic GVHD and relapse to prevail. In a previous 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 patients with high-risk hematologic malignancies and multiple comorbidities (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.

This new study seeks to test a similar strategy in a group of patients with high risk acute leukemia/myelodysplasia.

Study Overview

• Status: Completed
• Conditions: High Risk Hematological Malignancy; Cord Blood Transplant
• Intervention / Treatment: Biological: ECT-001-CB (UM171-Expanded Cord Blood Transplant)

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Gelderland
    • Rotterdam, Gelderland, Netherlands, 3015
      • Erasmus Medical Center
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado School of Medicine. Anschutz Medical Campus
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson / University of Washington Cancer Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. High and very high-risk hematologic malignancy defined as:

   1. Acute Myeloid Leukemia (Primary induction failure, Chemorefractory relapse, Relapse after allogeneic or autologous transplant, High risk AML in CR1, ≥ CR2)
   2. Acute Lymphoid leukemia (Primary induction failure, High risk ALL in CR1, ≥ CR2, Chemorefractory relapse, Relapse after allogeneic or autologous transplant)
   3. Myelodysplastic syndrome (Relapse after allogeneic or autologous transplant, ≥10% blasts within 30 days of start of conditioning regimen, Poor and very poor cytogenetics abnormalities, CMML with HCT-specific CPSS score high or intermediate-2, Stable disease, Progressive disease while on azacitidine).
   4. Chronic myelogenous leukemia (Patients who progressed to blast crisis)
2. Availability of 2 CBs ≥ 4/6 HLA match with pre-freeze CD34+ cell count ≥0.5 x 10E5/kg and TNC≥1.5 x 10E7/kg
3. Karnofsky ≥70.
4. LVE fraction ≥ 40% or fractional shortening >22%
5. FVC, FEV1 and DLCOc ≥ 50% of predicted
6. Bilirubin < 2 x ULN; AST and ALT ≤ 2.5 x ULN; alkaline phosphatase ≤ 5 x ULN.
7. Creatinine < 2.0 mg/dl.
8. HCT-CI ≤3 if patients have ≥5% blasts in the bone marrow and HCT-CI ≤5 if 60-65 years old.

Exclusion Criteria:

1. Allogeneic myeloablative transplant within 6 months.
2. Autologous hematopoietic stem cell transplant within 6 months.
3. Active or recent invasive fungal infection.
4. Presence of a malignancy other than the one for which the UCB transplant is being performed and the expected survival related to the malignancy is estimated to be less than 75% at 5 years.
5. HIV positivity.
6. Hepatitis B or C infection with measurable viral load.
7. Liver cirrhosis.
8. Pregnancy, breastfeeding or unwillingness to use appropriate contraception.
9. Any abnormal condition or laboratory result that is considered by the principal investigator capable of altering patient condition or study outcome.
10. Active central nervous system involvement.
11. Chloroma > 2 cm.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: ECT-001-Expanded CB; Patients will receive a myeloablative conditioning regimen. 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. Patients will receive standard supportive care and GVHD prophylaxis (such as MMF and tacrolimus).

Biological: ECT-001-CB (UM171-Expanded Cord Blood Transplant); Conditioning: High dose TBI (1320 cGy TBI + Fludarabine 75 mg/m2 + Cyclophosphamide 120 mg/kg) or Intermediate Intensity regimen (400 cGy TBI + Fludarabine 150 mg/m2 + Cyclophosphamide 50 mg/kg + Thiotepa 10 mg/kg). Single UM171-Expanded CB transplant (CD34+: 2.5-50x10E5/kg, CD3+>1x10E6/kg) Immunosuppression: Tacrolimus/MMF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse-free survival	RFS will be measured from time of transplant until disease relapse, death or last follow-up	At 1-year post-transplant
Relapse-free survival	RFS will be measured from time of transplant until disease relapse, death or last follow-up	At 2-year post-transplant
Adverse events of ECT-001-CB	All AEs will be graded in severity according to the modified (for HSCT) CTCAE (v. 5.0)	100 days post-transplant
Adverse events of ECT-001-CB	All AEs will be graded in severity according to the modified (for HSCT) CTCAE (v. 5.0)	2 years post-transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Neutrophil and Platelet engraftment	Neutrophil engraftment (the first day of attainment of an absolute neutrophil count ≥0.5 x 10E9/L for 3 consecutive days. Time to ANC ≥ 0.1 x 10E9/L will also be documented) and platelet engraftment (first day of a sustained platelet count ≥ 20 x 10E9/L with no platelet transfusion in the preceding 7 days)	First 60 days
Incidence of GVHD	Acute and chronic GVHD by NIH criteria	At 2 years post-transplant
Incidence of grade 3 or higher infectious complications	Any of infections requiring systemic therapy, e.g., invasive candidiasis, aspergillus, other invasive fungi, CMV, adenovirus, EBV, HHV-6, HSV, VZV, PCP, toxoplasmosis and mycobacterium	At 2 years post-transplant
Incidence of pre-engraftment/engraftment syndrome requiring therapy		At 2 years post-transplant
Incidence of transplant related mortality	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	At day 100 post-transplant
Incidence of transplant related mortality	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	At 1-year post-transplant
GRFS and CRFS	GRFS and CRFS will be measured from time of transplant until disease relapse, death or last follow-up	At 1-year post-transplant
GRFS and CRFS	GRFS and CRFS will be measured from time of transplant until disease relapse, death or last follow-up	At 2-year post-transplant

Collaborators and Investigators

• Sponsor: ExCellThera inc.
• Collaborators: Fred Hutchinson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2020
• Primary Completion (Actual): February 28, 2026
• Study Completion (Actual): February 28, 2026

Study Registration Dates

• First Submitted: September 23, 2019
• First Submitted That Met QC Criteria: September 24, 2019
• First Posted (Actual): September 26, 2019

Study Record Updates

• Last Update Posted (Actual): March 23, 2026
• Last Update Submitted That Met QC Criteria: March 20, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Hematologic Diseases; Precancerous Conditions; Bone Marrow Diseases; Hematologic Neoplasms; Preleukemia; Myelodysplastic Syndromes
• Other Study ID Numbers: ECT-001-CB.004; Study 8743 (Other Identifier: FHCRC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No