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NCT Number: NCT04103879

US Study of UM171-Expanded CB in Patients With High Risk 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.

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Key information

Conditions

High Risk Hematological Malignancy Cord Blood Transplant

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Erasmus Medical Center, Rotterdam, Gelderland, Netherlands

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • High and very high-risk hematologic malignancy defined as:
  • Acute Myeloid Leukemia (Primary induction failure, Chemorefractory relapse, Relapse after allogeneic or autologous transplant, High risk AML in CR1, ≥ CR2)
  • Acute Lymphoid leukemia (Primary induction failure, High risk ALL in CR1, ≥ CR2, Chemorefractory relapse, Relapse after allogeneic or autologous transplant)
  • 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).
  • Chronic myelogenous leukemia (Patients who progressed to blast crisis)
  • 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
  • Karnofsky ≥70.
  • LVE fraction ≥ 40% or fractional shortening >22%
  • FVC, FEV1 and DLCOc ≥ 50% of predicted
  • Bilirubin < 2 x ULN; AST and ALT ≤ 2.5 x ULN; alkaline phosphatase ≤ 5 x ULN.
  • Creatinine < 2.0 mg/dl.
  • HCT-CI ≤3 if patients have ≥5% blasts in the bone marrow and HCT-CI ≤5 if 60-65 years old.

Exclusion criteria

  • Allogeneic myeloablative transplant within 6 months.
  • Autologous hematopoietic stem cell transplant within 6 months.
  • Active or recent invasive fungal infection.
  • 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.
  • HIV positivity.
  • Hepatitis B or C infection with measurable viral load.
  • Liver cirrhosis.
  • Pregnancy, breastfeeding or unwillingness to use appropriate contraception.
  • Any abnormal condition or laboratory result that is considered by the principal investigator capable of altering patient condition or study outcome.
  • Active central nervous system involvement.
  • Chloroma > 2 cm.

Treatment and study plan

ECT-001-CB (UM171-Expanded Cord Blood Transplant)

Biological

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

Primary outcomes

  1. Adverse events of ECT-001-CB

    Time frame: 100 days post-transplant

    All AEs will be graded in severity according to the modified (for HSCT) CTCAE (v. 5.0)

  2. Adverse events of ECT-001-CB

    Time frame: 2 years post-transplant

    All AEs will be graded in severity according to the modified (for HSCT) CTCAE (v. 5.0)

  3. Relapse-free survival

    Time frame: At 1-year post-transplant

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

  4. Relapse-free survival

    Time frame: At 2-year post-transplant

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

Secondary outcomes

  1. Time to Neutrophil and Platelet engraftment

    Time frame: First 60 days

    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)

  2. Incidence of transplant related mortality

    Time frame: At day 100 post-transplant

    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

  3. Incidence of transplant related mortality

    Time frame: At 1-year post-transplant

    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

  4. Incidence of GVHD

    Time frame: At 2 years post-transplant

    Acute and chronic GVHD by NIH criteria

  5. Incidence of grade 3 or higher infectious complications

    Time frame: At 2 years post-transplant

    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

  6. Incidence of pre-engraftment/engraftment syndrome requiring therapy

    Time frame: At 2 years post-transplant

  7. GRFS and CRFS

    Time frame: At 1-year post-transplant

    GRFS and CRFS will be measured from time of transplant until disease relapse, death or last follow-up

  8. GRFS and CRFS

    Time frame: At 2-year post-transplant

    GRFS and CRFS will be measured from time of transplant until disease relapse, death or last follow-up

Sponsors and collaborators

Lead sponsor

ExCellThera inc.

Industry

Collaborators

  • Fred Hutchinson Cancer Center

Registry information

Official study title

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

Important dates

Study start
2020
Primary completion
2026
Study completion
2026
First posted
Sep 26, 2019
Registry last updated
Mar 23, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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