High-Risk and Very High-Risk Paediatric Myeloid Malignancies
Conditions
Interventions
Product Code: ECT-001-CB
Pharmaceutical Form: Dispersion for infusion
Sponsors
Cordex Biolohics Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Acute Myeloid Leukemia a) Chemo-refractory relapse (MRD+) b) Primary induction failure (no CR or CRi after >= 2 courses of intensive induction therapy): 4 months from previous transplant) d) Secondary or therapy-related MDS/AML e) Poor response to induction (5-30% blasts) or MRD+ after induction 2) Myelodysplastic syndrome (MDS) a) Relapse after allogeneic or autologous transplant (Note: ECB-001-CB transplant to take place >4 months from previous transplant) b) =10 % blasts within 30 days of start of conditioning regimen c) Poor and very poor cytogenetics abnormalities and very high-risk molecular abnormalities (e.g., TP53) 3) Chronic myelogenous leukemia: Patients with history of blast crisis or accelerated phase 4) Mixed Phenotype Acute Leukemia: MRD+ or relapse after previous transplant (>4 months). 5) JMML (Juvenile Myelo-Monocytic Leukemia) 6) 0 – 21 years 7) Availability of 2 = 4/8 HLA matched CBU (allele level: A, B, C and DRB1) a) Cord to be expanded: CD34+ cell count = 0.5 x 10E5/kg and TNC = 1.5 x 10E7/kg (pre-cryo) b) Back up cord: Pre-freeze TNC = 2 x 10E7/kg with CD34+ cells = 1 x 10E5/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 10E7 TNC/kg and 1 x 10E5/kg CD34+ cells. Another acceptable HSC back up source could be a haploidentical with medical clearance prior to starting conditioning regimen. 7) Lansky / Karnofsky >60% 8) Bilirubin = 50% of predicted. In young children unable to perform pulmonary function testing: pulse oximetry >92% in room air and a normal CT of the chest 12) Signed written informed consent (parents or legal guardians for minor patients). 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. Are the trial subjects under 18? yes Number of subjects for this age range: 15 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 20-30 days prior to the date of transplant (infusion of the expanded CD34+ cells): for investigation agents with half-life 1 day: patient must be off the Investigational agent for 30 days. 12) No signed informed consent. 13) Any abnormal condition or lab result that is considered by the PI capable or altering patient’s condition or study outcome.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1)Examine the safety and feasibility of infusing a single ECT-001-expanded cord blood in pediatric and young adult patients with high and very high-risk myeloid malignancies 2)Evaluate incidence of relapse at 1-year post-transplant ;Secondary Objective: 1)Evaluate leukemia free survival at 1- and 2-years after transplantation 2)Kinetics of hematologic engraftment 3)Non-Relapse Mortality at Day 100 and at 1-year 4)Incidence of acute and chronic GVHD by NIH criteria at 1- and 2-years post-transplant 5)Incidence of grade 3 or higher infectious complications 6)Hospitalization events: Duration of transplant admission and number of days in hospital in 1st 100 days, and last day of fever (>38°C) prior to engraftment. 7)Incidence of pre-engraftment/engraftment syndrome (PES/ES) requiring therapy 8)Immune reconstitution: CD4 counts, CD8 counts, IgG levels 9)Quality of Life evaluation ;Primary end point(s): 1) Safety and feasibility of infusing a single ECT-001-expanded blood cord (AEs, ADRs, SAEs) 2) Relapse at 1-year post-transplant ;Timepoint(s) of evaluation of this end point: 1) Throughout trial 2) 1-year post-transplant | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) LFS, OS 2) Kinetics of hematopoietic engraftment (neutrophil engraftment, platelet engraftment, graft failuire) 3) NRM 4) Acute and chronic GVHD 5) Severe infectious complications 6) Hospitalization events 7) ES/PES requiring therapy 8) Immune reconstitution 9) Quallity of life;Timepoint(s) of evaluation of this end point: 1) 1- and 2-year post-transplant 2) Day 45 for neuts, Day 100 for platelets 3) Day 100 and 1-year post-transplant 4) Day 100 and 1-year post-transplant (aGVHD), 1- and 2-year post-transplant (cGVHD) 5) Througout trial 6) Throughout trial 7) Throughout trial 8) Days 30, 60 and Months 3, 6, 12 post-transplant 9) Months 3, 6, 12, 24 post-transplant | — |
Countries
United States
Contacts
Public ContactPierre Caudrelier
Cordex Biologics Inc
Outcome results
None listed