Hematological Malignancies
Conditions
Brief summary
Omidubicel is an investigational therapy for patients with high-risk hematologic malignancies.
Detailed description
Successful blood and marrow transplantation (BMT) requires the infusion of a sufficient number of hematopoietic stem/progenitor cells (HSPCs), capable of both homing to the bone marrow and regenerating a full array of hematopoietic cell lineages with early and late repopulating ability in a timely fashion. Omidubicel is a stem/progenitor cell-based product composed of ex vivo expanded allogeneic cells from one entire unit of umbilical cord blood consisting of mature myeloid and lymphoid cells as follows: 1. Ex vivo expanded, umbilical cord blood-derived hematopoietic CD34+ progenitor cells (cultured fraction (CF)), containing a minimum of 8.0 × 10\^8 total viable cells of which a minimum of 8.7% is CD34+ cells and a minimum of 9.2 × 10\^7 CD34+ cells, and 2. the non-cultured cell fraction of the same Cord Blood Unit (CBU) (Non-cultured Fraction (NF)), containing a minimum of 4.0 × 10\^8 total viable cells with a minimum of 2.4 × 10\^7 CD3+ cells Omidubicel utilizes the small molecule nicotinamide (NAM), as an epigenetic approach to inhibit differentiation and to increase the migration, bone marrow (BM) homing and engraftment efficiency of hematopoietic progenitor cells (HPC) expanded in ex vivo cultures. The overall study objectives are to provide access to omidubicel for transplantation in patients with hematological malignancies and to collect additional safety and efficacy data.
Interventions
BIOLOGICALomidubicel
hematopoietic stem cell transplant
Sponsors
Gamida Cell ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must be at least 12 years of age * Applicable disease criteria * Patients must have one or two partially HLA-matched CBUs * Back-up stem cell source * Sufficient physiological reserves * Females of childbearing potential agree to use appropriate method of contraception * Signed written informed consent
Exclusion criteria
* Extensive bone marrow fibrosis * Donor specific anti-HLA antibodies * Pregnancy * Medically unsuitable for transplant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time From Transplant to Neutrophil Engraftment | by day 42 post-transplant inclusive | Neutrophil engraftment was defined as achieving an absolute neutrophil count (ANC) greater than or equal to 0.5 x 10\^9/L on 3 consecutive measurements by Day 42 post-transplant inclusive. The first day of the three measurements was designated the day of neutrophil engraftment. |
| Cumulative Incidence of Neutrophil Engraftment | by day 42 post-transplant inclusive | Death, second transplant, and relapse were competing risks at the time they occur if they occur prior to neutrophil engraftment, and no transplant was a competing risk at Day 0. If the patient failed to achieve neutrophil engraftment, they were considered to have a competing risk at Day 43. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Incidence of Platelet Engraftment >20,000 Cells/uL | By Day 42 and Day 180 post-transplant | — |
| Time to Platelet Engraftment >20,000 Cells/uL | By Day 730 post-transplant | Time to platelet engraftment \>20,000 cells/ul was defined as the number of days from transplant to the first day of a minimum of 3 consecutive measurements on different days in which the platelet count is 20,000 cells/ul or higher with no platelet transfusion within the previous 7 days (count day of engraftment as one of the preceding 7 days) was calculated. The first day of the three measurements was designated the day of platelet engraftment. |
| Cumulative Incidence of Platelet Engraftment >50,000 Cells/uL | By Day 42 and Day 180 post-transplant | — |
| Time to Platelet Engraftment >50,000 Cells/uL | By Day 730 post-transplant | Time to platelet engraftment \>50,000 cells/ul was defined as the number of days from transplant to the first day of a minimum of 3 consecutive measurements on different days in which the platelet count is 50,000 cells/ul or higher with no platelet transfusion within the previous 7 days (count day of engraftment as one of the preceding 7 days) was calculated. The first day of the three measurements was designated the day of platelet engraftment. |
| Non-relapse Mortality | By Day 180, Day 365 and Day 730 post-transplant | Non-relapse mortality was defined as any death not preceded by relapse. |
| Overall Survival (OS) | By Day 180, Day 365 and Day 730 post-transplant | OS probability was defined as the probability of participants remaining alive at specified time points following transplantation, estimated using Kaplan-Meier methods. |
| Disease Free Survival (DFS) | By Day 365 and Day 730 post-transplant | Disease-free survival was defined as the survival without disease relapse or death from any cause, whichever came first. |
| Donor Chimerism | By day 100 and Day 730 post-transplant | Patients considered to have donor chimerism when they had at least 95% donor chimerism |
| Secondary Graft Failure (SGF) | By Day 730 post-transplant | — |
| Disease Relapse | By Day 365 and Day 730 post-transplant | — |
| Cumulative Incidence of Acute GvHD Grade II-IV | By Day 100 post-transplant | Death, failure to achieve neutrophil engraftment, secondary graft failure, and relapse were considered competing events. |
| Cumulative Incidence of aGvHD Grade III-IV | By Day 100 post-transplant | Death, failure to achieve neutrophil engraftment, secondary graft failure, and relapse were considered competing events. |
| Cumulative Incidence of Chronic GvHD | By Day 180 and Day 730 post-transplant | Death, failure to achieve neutrophil engraftment, secondary graft failure, and relapse were considered competing events. |
| Chronic GvHD-free Relapse-free Survival (cGRFS) | By Day 365 and Day 730 post-transplant | Chronic graft versus host disease-free, relapse-free survival (cGRFS) was defined as chronic GvHD, relapse, or death by any cause. |
| GvHD-free Relapse-free Survival (GRFS) | By Day 365 and Day 730 post-transplant | Graft versus host disease-free, relapse-free survival (GRFS) was defined as acute GvHD Grade III-IV, chronic GvHD, relapse, or death by any cause |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMitchell Horwitz, MD
Duke University
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 39.0 Years |
| Age, Customized Age at CBU shipment 12-17 years | 0 Participants |
| Age, Customized Age at CBU shipment 18-39 years | 15 Participants |
| Age, Customized Age at CBU shipment 40-59 years | 11 Participants |
| Age, Customized Age at CBU shipment 60-65 years | 0 Participants |
| Age, Customized Age at CBU shipment >65 years | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 23 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| HLA match (/6) 4/6 | 14 Participants |
| HLA match (/6) 5/6 | 13 Participants |
| HLA match (/6) 6/6 | 2 Participants |
| HLA match (/8) 4/8 | 4 Participants |
| HLA match (/8) 5/8 | 14 Participants |
| HLA match (/8) 6/8 | 7 Participants |
| HLA match (/8) 7/8 | 3 Participants |
| HLA match (/8) 8/8 | 1 Participants |
| Primary diagnosis Acute Lymphoblastic Leukemia (ALL) | 8 Participants |
| Primary diagnosis Acute Myelogenous Leukemia (AML) | 11 Participants |
| Primary diagnosis Adult T-Cell Leukemia/Lymphoma | 2 Participants |
| Primary diagnosis Chronic Myelogenous Leukemia (CML) | 1 Participants |
| Primary diagnosis Lymphoma | 1 Participants |
| Primary diagnosis Myelodysplastic Syndrome (MDS) / Chronic Myelomonocytic Leukemia (CMML/CMMoL) | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 6 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 16 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 6 / 29 |
| other Total, other adverse events | 29 / 29 |
| serious Total, serious adverse events | 21 / 29 |
Outcome results
None listed