Hemoglobinopathies MedDRA version: 18.0 Level: LLT Classification code 10054658 Term: Thalassemia System Organ Class: 100000004850 MedDRA version: 18.0 Level: LLT Classification code 10040645 Term: Sickle cell disease NOS System Organ Class: 100000004850
Conditions
Interventions
Product Name: CordIn (CF cultured fraction and NF non-cultured fraction)
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: allogeneic, umbilical cord blood-derived, ex vivo expanded,
Sponsors
Gamida Cell Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Patients must be 2–25 years of age and at least 10kg 2.Patient is a candidate for allogeneic SCT for treatment of SCD or thalassemia: a.Patient must have clinically severe SCD(eg. SS, SC or SBeta0 Thal) with at least one of the following clinical complications: Recurrent painful events(at least 3 in the 2 years prior to enrollment) that cannot be explained by other causes. Pain may occur in typical sites associated with vaso-occlusive painful events and cannot be explained by causes other than sickle cell disease. Pain lasts at least 4 hours and requires parenteral narcotic treatment,equianalgesic dose of oral narcotics or parenteral nonsteroidal anti-inflamrnatory drugs. These painful events may be treated in any setting,but events managed at home will be considered only if there is documentation of the event in a clinical record that may be reviewed by an investigator. These events must occur despite adequate supportive care measures. Acute chest syndrome with at least two episodes with the development of a new infiltrate on chest radiograph and/or having a perfusion defect demonstrable on a lung radioisotope scan within the past two years that required hospitalization, oxygen therapy, and RBC transfusion. These episodes must occur despite adequate supportive care measures. Any combination of painful events and acute chest syndrome episodes that total three events within the two years before transplantation. Any clinically significant neurologic event (stroke or hemorrhage) or any neurologic defect lasting more than 24 hours. Patients on chronic PRBC transfusion therapy, defined as receiving 8 or more transfusions per year for > 1 year to prevent vaso-occlusive clinical complications (e.g. pain, stroke, and acute chest syndrome) Abnormal cerebral MRI and abnormal cerebral MRA. Abnormal Transcranial Doppler (TCD), as defined by a TCD velocity that exceeds 200 cm/sec by the non-imaging technique (or TCD measurement of >185 cm/sec by the imaging technique) measured at a minimum of two separate occasions one month or more apart OR; b.Patient must have thalassemia major requiring regular RBC transfusions 3.Patients must have a partially HLA-matched CBU. The unit must be HLA-matched at 4-6/6 HLA class I (HLA-A & HLA-B, low resolution) and II (HLA-DRB1, high resolution) loci with the subject. For patients weighing = 25 kg, the CBU must have a pre-cryopreserved, total CD34+ cell dose of =10x10^6 as well as a pre-cryopreserved total nucleated cell dose of =1.8x10^9. For patients weighing 50% by echocardiogram radionuclide scan or cardiac MRI; or LV shortening fraction > 26%. Pulmonary: Pulse oximetry with a baseline O2 saturation of = 85% is required for all patients, DLCO > 60% of predicted for age (corrected for hemoglobin) for patients in whom pulmonary function testing can be performed. Renal: Serum creatinine = 1.5 x upper limit of normal for age and GFR >
Exclusion criteria
Exclusion criteria: 1.Evidence of uncontrolled bacterial, viral or fungal infections or severe concomitant diseases, which in the judgment of the Principal Investigator, indicate that the patient could not tolerate transplantation 2.Evidence of HIV infection or HIV positive serology 3.Evidence of active Hepatitis B, Hepatitis C or EBV as determined by serology or PCR 4.Pregnancy, as indicated by a positive serum human chorionic gonadotrophin (HCG) test, or lactation 5.Patients with 10/10 or 9/10 HLA-matched related family donor or unrelated donor able to donate 6.Severe alloimmunization with inability to guarantee a supply of adequate PRBC donors 7.Evidence of anti-HLA antibodies to the selected CordIn™ CBU (MFI>1000) 8.Prior allogeneic hematopoietic stem cell transplant within last 12 months . 9.Allergy to bovine, Gentamicin, or to any product which may interfere with the treatment 10.Psychologically incapable of undergoing bone marrow transplant (BMT) with associated strict isolation or documented history of medical non-compliance and/or psychiatric illness and/or social situations that would limit compliance with study requirements 11.Enrolled in another clinical trial or received an investigational treatment during the last 30 days, unless approved by Sponsor
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Assess the acute toxicities associated with the infusion of CordIn, within 24 hours post-infusion Assess the proportion of patients with donor-derived engraftment at 42 days following transplantation ;Secondary Objective: Cumulative incidence of transplant-related mortality at day 100 after transplantation Event-free survival at day 100 and 1 year after transplantation (patient’s death, autologous recovery, primary or secondary graft failure will be considered events for this endpoint) Overall survival at 1 year after transplantation (patient’s death will be considered the relevant event) RBC transfusion-free survival at 1 year in thalassemia patients Proportion of treatment free HbS = 30% at 1 year in SCD patients ;Primary end point(s): 1. acute toxicities associated with the infusion of CordIn™, within 24 hours post-infusion 2. proportion of patients with donor-derived engraftment at 42 days following transplantation;Timepoint(s) of evaluation of this end point: 1. 24 hours 2. day 42 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Cumulative incidence of transplant-related mortality at day 100 after transplantation 2. Event-free survival at day 100 and 1 year after transplantation (patient’s death, autologous recovery, primary or secondary graft failure will be considered events for this endpoint) 3. Overall survival at 1 year after transplantation (patient’s death will be considered the relevant event) 4. RBC transfusion-free survival at 1 year in thalassemia patients 5. Proportion of treatment free HbS = 30% at 1 year in SCD patients ;Timepoint(s) of evaluation of this end point: 1. day 100 2. day 100 and 1 year 3. 1 year 4. 1 year 5. 1 year | — |
Countries
France, Italy, United States
Contacts
Public ContactClinical Trial department
Gamida Cell Ltd
Outcome results
None listed