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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04990323
Recruitment Status : Recruiting
First Posted : August 4, 2021
Last Update Posted : January 13, 2022
Sponsor:
Collaborator:
Memorial Sloan Kettering Cancer Center
Information provided by (Responsible Party):
ExCellThera inc.

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).


Condition or disease Intervention/treatment Phase
High Risk Myeloid Malignancies Cord Blood Transplant Biological: ECT-001-CB (UM171-Expanded Cord Blood Transplant) Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : December 1, 2021
Estimated Primary Completion Date : April 1, 2023
Estimated Study Completion Date : April 1, 2024

Arm Intervention/treatment
Experimental: ECT-001-Expanded CB

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




Primary Outcome Measures :
  1. Adverse events of ECT-001-CB [ Time Frame: 100 days ]
    Incidence and severity of AEs according to the modified (for HSCT) CTCAE (v. 5.0)

  2. Relapse [ Time Frame: 1 year post-transplant ]
    Incidence of relapse will be measured from time of transplant


Secondary Outcome Measures :
  1. Leukemia-free survival [ Time Frame: 1- and 2-year post-transplant ]
    LFS will be measured from time of transplant until disease relapse, death or last follow-up

  2. Non-Relapse Mortality [ Time Frame: 1 year post-transplant ]
    NRM 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. GVHD [ Time Frame: 1- and 2-year post-transplant ]
    Incidence of acute and chronic GVHD will be measured by NIH criteria

  4. Grade 3 Infections [ Time Frame: 2-year post-transplant ]
    Incidence and severity of infections requiring systemic therapy, e.g., invasive candidiasis, aspergillus, other invasive fungi, CMV, adenovirus, EBV, HHV-6, HSV, VZV, PCP, toxoplasmosis and mycobacterium

  5. Hematologic engraftment [ Time Frame: 42 and 100 days ]
    Time to 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 time to platelet engraftment (first day of a sustained platelet count ≥ 50 x 10E9/L with no platelet transfusion in the preceding 7 days)

  6. Pre-engraftment/engraftment syndrome [ Time Frame: 2-year post-transplant ]
    Incidence of pre-engraftment/engraftment syndrome requiring therapy

  7. Hospitalization events [ Time Frame: 100 days ]
    Duration of transplant admission and number of days in hospital in 1st 100 days, and last day of fever (>38°C) prior to engraftment



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   0 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04990323


Contacts
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Contact: Jaap Jan Boelens, MD, PhD 212-639-3643 boelensj@mskcc.org
Contact: Andromachi Scaradavou, MD 212-639-3267 scaradaa@mskcc.org

Locations
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United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Andromachi Scaradavou, MD         
Contact: Jaap J Boelens, MD         
Sponsors and Collaborators
ExCellThera inc.
Memorial Sloan Kettering Cancer Center
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Responsible Party: ExCellThera inc.
ClinicalTrials.gov Identifier: NCT04990323    
Other Study ID Numbers: ECT-001-CB.007
First Posted: August 4, 2021    Key Record Dates
Last Update Posted: January 13, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Supporting Materials: Clinical Study Report (CSR)

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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
Additional relevant MeSH terms:
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Neoplasms
Vidarabine
Cyclophosphamide
Busulfan
Thiotepa
Fludarabine
Fludarabine phosphate
Clofarabine
Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Calcineurin Inhibitors
Enzyme Inhibitors