Using expanded cord blood transplants for young patients with high-risk blood cancers

A Phase I/II Open-Label Study of ECT-001-Expanded Cord Blood Transplantation in Pediatric and Young Adult (<21year) Patients With High-Risk and Very High-Risk Myeloid Malignancies

This study is testing a new way to use expanded cord blood transplants to see if they can help young patients with high-risk blood cancers recover better and have fewer complications.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 0 Years to 21 Years
• Sex: All
• Sponsor: ExCellThera inc. (industry)
• Locations: 1 site (New York, New York)
• Trial ID: NCT04990323 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the use of ECT-001-CB, a novel technology that expands cord blood for transplantation in pediatric and young adult patients with high-risk myeloid malignancies. The study aims to address limitations of traditional cord blood transplants, such as low cell doses and high transplant-related mortality, by utilizing UM171, a potent agonist that enhances hematopoietic stem cell self-renewal. Previous trials have shown that this approach is technically feasible and safe in adults, with promising outcomes in neutrophil recovery and reduced complications. The trial will evaluate the effectiveness and safety of this method in a younger population.

Who should consider this trial

Good fit: Ideal candidates include pediatric and young adult patients with acute myeloid leukemia, myelodysplastic syndrome, chronic myelogenous leukemia, mixed phenotype acute leukemia, or juvenile myelo-monocytic leukemia who meet specific eligibility criteria.

Not a fit: Patients with low-risk myeloid malignancies or those who do not have available HLA-matched cord blood units may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve transplant outcomes and reduce complications for young patients with high-risk myeloid malignancies.

How similar studies have performed: Previous studies using similar cord blood expansion techniques have shown promising results in adult populations, indicating potential for success in this pediatric trial.

Eligibility criteria

Inclusion Criteria:

1. Acute Myeloid Leukemia

   1. Chemo-refractory relapse (MRD+)
   2. Primary induction failure (no CR or CRi after \>= 2 courses of intensive induction therapy): \< 30% blasts in evaluable marrow.
   3. Relapse after previous allogeneic (or autologous) transplant (\>4 months)
   4. Secondary or therapy-related MDS/AML
   5. Poor response to induction (5-30% blasts) or MDR+ after induction
2. Myelodysplastic syndrome (MDS)

   1. Relapse after allogeneic or autologous transplant (\>4 months)
   2. ≥10 % blasts within 30 days of start of conditioning regimen
   3. Poor and very poor cytogenetics abnormalities
3. Chronic myelogenous leukemia: Patients who progressed to blast crisis
4. Mixed Phenotype Acute Leukemia: MRD+ or relapse after previous transplant (\>4 months).
5. JMML (Juvenile Myelo-Monocytic Leukemia)
6. Availability of 2 ≥ 4/8 HLA matched CBU (allele level: A, B, C and DRB1)

   1. Cord to be expanded: CD34+ cell count ≥ 0.5 x 10\^5/kg and TNC ≥ 1.5 x 10\^7/kg (pre-cryo)
   2. Back up cord: Pre-freeze TNC ≥ 2 x 10\^7/kg with CD34+ cells ≥ 1.5 x 10\^5/kg. If a single cord does not meet this criterion 2 back up cords will be an acceptable alternative with a minimum for each of 1.5 x 10\^7 TNC/kg with 1.0 x 10\^5 CD34+/kg. Another acceptable HSC back up source could be a haploidentical with medical clearance prior to starting conditioning regimen.
7. Lansky / Karnofsky \>60%
8. Bilirubin \< 2 x upper limit of normal (ULN) unless felt to be related to Gilbert's disease or hemolysis; AST and ALT \< 3 x ULN; alkaline phosphatase \< 5 x ULN
9. Estimated or measured creatinine clearance ≥ 50ml/min/1.73m2
10. Left ventricular ejection fraction of ≥ 40%
11. FVC, FEV1 and DLCO ≥ 50% of predicted
12. Signed written informed consent
13. Female patients of childbearing potential must have a negative serum pregnancy test within 7 days of enrolment and mush be willing to use an effective contraceptive method while enrolled in the study.

Exclusion Criteria:

1. Previous allogeneic transplantation within 4 months.
2. Uncontrolled infection.
3. 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
4. Seropositive for HIV.
5. Hep B and C infection with measurable viral load.
6. Liver cirrhosis.
7. Active CNS disease.
8. Chloroma \> 2cm.
9. \>30% blasts in marrow in evaluable marrow sample.
10. Pregnancy, breastfeeding, or unwillingness to use appropriate contraception
11. Participation in a trial with an investigational agent within 30days prior to entry in the study.
12. Any abnormal condition or lab result that is considered by the PI capable or altering patient's condition or study outcome.

Where this trial is running

New York, New York

• Memorial Sloan Kettering Cancer Center — New York, New York, United States (RECRUITING)

Study contacts

• Study coordinator: Jaap Jan Boelens, MD, PhD

Conditions: High Risk Myeloid Malignancies, Cord Blood Transplant