- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04990323
US Study of ECT-001-CB in Pediatric and Young Adult Patients With High-Risk Myeloid Malignancies
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
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).
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Jaap Jan Boelens, MD, PhD
- Phone Number: 212-639-3643
- Email: boelensj@mskcc.org
Study Contact Backup
- Name: Andromachi Scaradavou, MD
- Phone Number: 212-639-3267
- Email: scaradaa@mskcc.org
Study Locations
-
-
New York
-
New York, New York, United States, 10065
- Recruiting
- Memorial Sloan Kettering Cancer Center
-
Contact:
- Andromachi Scaradavou, MD
-
Contact:
- Jaap J Boelens, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
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)
- 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.
- Lansky / Karnofsky >60%
- 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
- Estimated or measured creatinine clearance ≥ 50ml/min/1.73m2
- Left ventricular ejection fraction of ≥ 40%
- FVC, FEV1 and DLCO ≥ 50% of predicted
- Signed written informed consent
- 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:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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). |
Single UM171-Expanded CB transplant (CD34+: 2.5-50x10^5/kg, CD3+>1x10^6/kg)
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
|
100 days
|
Relapse
Time Frame: 1 year post-transplant
|
Incidence of relapse will be measured from time of transplant
|
1 year post-transplant
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
1- and 2-year post-transplant
|
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
|
1 year post-transplant
|
GVHD
Time Frame: 1- and 2-year post-transplant
|
Incidence of acute and chronic GVHD will be measured by NIH criteria
|
1- and 2-year post-transplant
|
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
|
2-year post-transplant
|
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)
|
42 and 100 days
|
Pre-engraftment/engraftment syndrome
Time Frame: 2-year post-transplant
|
Incidence of pre-engraftment/engraftment syndrome requiring therapy
|
2-year post-transplant
|
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
|
100 days
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Calcineurin Inhibitors
- Cyclophosphamide
- Clofarabine
- Fludarabine
- Fludarabine phosphate
- Tacrolimus
- Thiotepa
- Busulfan
- Vidarabine
Other Study ID Numbers
- ECT-001-CB.007
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Sharing Supporting Information Type
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cord Blood Transplant
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI); RevimmuneWithdrawnRecombinant Human Interleukin-7 (CYT107) to Promote T-Cell Recovery After Cord Blood TransplantationUmbilical Cord Blood Transplant
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)CompletedHematopoietic Cell Transplantation Recipient | Bone Marrow Transplantation Recipient | Cord Blood Transplant RecipientUnited States
-
Cancer Institute and Hospital, Chinese Academy...UnknownComplications of Organ Transplant Stem Cells Umbilical CordChina
-
Nanfang Hospital, Southern Medical UniversityRecruitingLeukemia | Stem Cell Transplant | Cord BloodChina
-
Baylor College of MedicineCenter for Cell and Gene Therapy, Baylor College of MedicineWithdrawnLymphoid Hematological Malignancies | Umbilical Cord Blood Transplant
-
Tarix PharmaceuticalsWithdrawnHematologic Malignancy | Cord Blood Transplant | Inherited Metabolic DiseaseUnited States
-
Ciusss de L'Est de l'Île de MontréalExCellThera inc.; Stem Cell NetworkActive, not recruitingCord Blood Transplant | High Risk Hematologic MalignancyCanada
-
ExCellThera inc.Fred Hutchinson Cancer CenterActive, not recruitingHigh Risk Hematological Malignancy | Cord Blood TransplantUnited States, Netherlands
-
National Institute of Allergy and Infectious Diseases...Clinical Trials in Organ Transplantation in ChildrenCompletedLiver Transplant | Kidney Transplant | Heart Transplant | EBV-Related PTLD | Small Intestine Transplant | PTLDsUnited States
-
Stanford UniversityRecruitingBlood and Marrow Transplant (BMT)United States
Clinical Trials on ECT-001-CB (UM171-Expanded Cord Blood Transplant)
-
ExCellThera inc.California Institute for Regenerative Medicine (CIRM)WithdrawnSickle Cell Disease | Umbilical Cord Blood | Hematopoietic Cell ProliferationUnited States
-
ExCellThera inc.Fred Hutchinson Cancer CenterActive, not recruitingHigh Risk Hematological Malignancy | Cord Blood TransplantUnited States, Netherlands
-
Ciusss de L'Est de l'Île de MontréalExCellThera inc.; Centre C3iActive, not recruitingMultiple MyelomaCanada
-
Ciusss de L'Est de l'Île de MontréalExCellThera inc.; Stem Cell NetworkActive, not recruitingCord Blood Transplant | High Risk Hematologic MalignancyCanada
-
Maisonneuve-Rosemont HospitalCanadian Institutes of Health Research (CIHR); Hopital de l'Enfant-Jesus; St.... and other collaboratorsCompletedHematologic MalignancyCanada
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)RecruitingRecurrent Gliosarcoma | Recurrent Supratentorial Glioblastoma | Supratentorial GliosarcomaUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI); CellgenixCompletedLymphoma, Non-Hodgkin | Leukemia, Lymphocytic, Acute | Leukemia, Myelocytic, Acute | Leukemia, Myeloid, ChronicUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)RecruitingRefractory Malignant Solid Neoplasm | Recurrent Malignant Solid Neoplasm | Recurrent Cutaneous Melanoma | Recurrent Malignant Female Reproductive System Neoplasm | Refractory Malignant Female Reproductive System Neoplasm | Recurrent Lip and Oral Cavity Carcinoma | Recurrent Malignant Endocrine... and other conditionsUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)CompletedMantle Cell Lymphoma | Recurrent Diffuse Large B-Cell Lymphoma | Refractory Diffuse Large B-Cell Lymphoma | Refractory Indolent Adult Non-Hodgkin Lymphoma | Recurrent Follicular Lymphoma | Refractory Follicular Lymphoma | Recurrent Indolent Adult Non-Hodgkin LymphomaUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)UnknownRecurrent Hodgkin Lymphoma | Refractory Hodgkin Lymphoma | Secondary Acute Myeloid Leukemia | Myelodysplastic Syndrome | Recurrent Acute Myeloid Leukemia | Recurrent Small Lymphocytic Lymphoma | Refractory Chronic Lymphocytic Leukemia | Recurrent Non-Hodgkin Lymphoma | Refractory Non-Hodgkin Lymphoma | Recurrent Acute Lymphoblastic Leukemia and other conditionsUnited States