US Study of ECT-001-CB in Pediatric and Young Adult Patients With High-Risk Myeloid Malignancies

NCT04990323 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: ECT-001-CB.007
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

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 previous trials (NCT02668315, NCT03913026, NCT04103879, and NCT03441958), the CB expansion protocol using the ECT-001-CB technology (UM171 molecule) has proven to be technically feasible and safe in adults. UM171 expanded CB was associated with a prompt (D+17), robust (98%) and durable neutrophil recovery. Amongst patients who received a single UM171 CB transplant with a median follow-up of 18 months, risk of TRM (10%), grade 3-4 acute GVHD (13%) and moderate-severe chronic GVHD (2%) was low at 1 year post-transplant. Incidence of severe viral and bacterial infections was reduced and immunosuppression could be discontinued in 77% of patients at 1 year. Thus, PFS and GRFS were very promising, 72% and 59% at 12 months, 69% and 53% at 24 months, respectively, in particular accounting for a large proportion of very high-risk patients. By a 10-fold increase of CB accessibility, ECT-001-CB allowed access to smaller, better HLA matched CBs. This new study seeks to test a similar strategy in a group of pediatric and young adult patients with high risk myeloid malignancies. 12 patients will be enrolled in the first stage of this 2-stage design protocol. If intervention is considered promising (\<= 3 relapses in the first 12 patients), this study will open multicenter and be extended to a second stage (16 additional patients for a total accrual 28).

Conditions

High Risk Myeloid Malignancies; Cord Blood Transplant

Outcome Measures

Primary Outcomes (2)

• Adverse events of ECT-001-CB

  Incidence and severity of AEs according to the modified (for HSCT) CTCAE (v. 5.0)

  100 days

• Relapse

  Incidence of relapse will be measured from time of transplant

  1 year post-transplant

Secondary Outcomes (7)

• Leukemia-free survival

  1- and 2-year post-transplant

• Non-Relapse Mortality

  1 year post-transplant

• GVHD

  1- and 2-year post-transplant

• Grade 3 Infections

  2-year post-transplant

• Hematologic engraftment

  42 and 100 days

Study Arms (1)

ECT-001-Expanded CB

EXPERIMENTAL

Patients will receive a myeloablative conditioning regimen (Preferred: Clo/Flu/Bu90, Alternative: MIDI) 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)

Interventions

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

Single UM171-Expanded CB transplant (CD34+: 2.5-50x10\^5/kg, CD3+\>1x10\^6/kg)

Also known as: Conditioning Regimen (Preferred): clofarabine:30 mg/m2/day IV x 4 days, fludarabine:10 mg/m2/day IV x 4 days, busulfan: daily for 4 days with cumm Bu target = 90mg h/L, Conditioning Regimen (Alternative): MIDI: fludarabine: 30 mg/m2/day IV x 5 days, cyclophosphamide: 50 mg/kg IV , thiotepa: 5 mg/kg/day IV x 2 days , TBI: 400 cGy, GVHD Prophylaxis: Tacrolimus/MMF

ECT-001-Expanded CB

Eligibility Criteria

• Age: 0 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Acute Myeloid Leukemia
• Chemo-refractory relapse (MRD+)
• Primary induction failure (no CR or CRi after \>= 2 courses of intensive induction therapy): \< 30% blasts in evaluable marrow.
• Relapse after previous allogeneic (or autologous) transplant (\>4 months)
• Secondary or therapy-related MDS/AML
• Poor response to induction (5-30% blasts) or MDR+ after induction
• Myelodysplastic syndrome (MDS)
• Relapse after allogeneic or autologous transplant (\>4 months)
• ≥10 % blasts within 30 days of start of conditioning regimen
• Poor and very poor cytogenetics abnormalities
• Chronic myelogenous leukemia: Patients who progressed to blast crisis
• Mixed Phenotype Acute Leukemia: MRD+ or relapse after previous transplant (\>4 months).
• JMML (Juvenile Myelo-Monocytic Leukemia)
• Availability of 2 ≥ 4/8 HLA matched CBU (allele level: A, B, C and DRB1)
• Cord to be expanded: CD34+ cell count ≥ 0.5 x 10\^5/kg and TNC ≥ 1.5 x 10\^7/kg (pre-cryo)

You may not qualify if:

• Previous allogeneic transplantation within 4 months.
• Uncontrolled infection.
• Presence of other malignancy other than the one for which the CB transplant is being performed, with an expected survival to be less than 75% at 5 years
• Seropositive for HIV.
• Hep B and C infection with measurable viral load.
• Liver cirrhosis.
• Active CNS disease.
• Chloroma \> 2cm.
• \>30% blasts in marrow in evaluable marrow sample.
• Pregnancy, breastfeeding, or unwillingness to use appropriate contraception
• Participation in a trial with an investigational agent within 30days prior to entry in the study.
• Any abnormal condition or lab result that is considered by the PI capable or altering patient's condition or study outcome.

Sponsors & Collaborators

• ExCellThera inc.: lead
• Memorial Sloan Kettering Cancer Center: collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

MeSH Terms

Interventions

Transplantation Conditioning; Cyclophosphamide; Thiotepa

Intervention Hierarchy (Ancestors)

Immunosuppression Therapy; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2021
• First Posted: August 4, 2021
• Study Start: December 1, 2021
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: March 24, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR

Locations

US (1)