Acute Leukemia, Acute Lymphoblastic Leukemia (ALL), Acute Myelogenous Leukemia (AML), Chronic Myelogenous Leukemia (CML), Hematological Malignancies, Lymphoma, Myelodysplastic Syndrome (MDS)
Conditions
Brief summary
This study is an open-label, controlled, multicenter, international, Phase III, randomized study of transplantation of NiCord® versus transplantation of one or two unmanipulated, unrelated cord blood units in patients with acute lymphoblastic leukemia or acute myeloid leukemia, myelodysplastic syndrome, chronic myeloid leukemia or lymphoma, all with required disease features rendering them eligible for allogeneic transplantation.
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. A major drawback of Umbilical Cord Blood (UCB) is the low stem cell dose available for transplantation, compared to mobilized peripheral blood (PB) or bone marrow. This low stem cell dose can compromise the chances of engraftment and contributes to delayed kinetics of neutrophil and platelet recovery, as well as other transplant outcomes. The aim of ex vivo expansion of cord blood is to provide a graft with sufficient numbers of cells that have rapid and robust in vivo neutrophil and platelet producing potential to enable successful transplantation. NiCord® is a stem/progenitor cell-based product composed of ex vivo expanded allogeneic cells from one entire unit of UCB. NiCord® 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 chief aim of the study is to compare the safety and efficacy of NiCord® single ex-vivo expanded cord blood unit transplantation to unmanipulated cord blood unit transplantation in patients with hematological malignancies following conditioning therapy.
Interventions
DRUGNiCord® (omidubicel)
OTHERCord Blood Unit
Cord blood unit
Sponsors
Gamida Cell ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Applicable disease criteria * Patients must have one or two partially HLA-matched CBUs * Back-up stem cell source * Adequate Karnofsky/Lansky Performance score * Sufficient physiological reserves * Signed written informed consent
Exclusion criteria
* HLA-matched donor able to donate * Prior allogeneic HSCT * Other active malignancy * Active or uncontrolled infection * Active/symptoms of central nervous system (CNS) disease * Pregnancy or lactation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Neutrophil Engraftment | post-transplant up to 42 days | The time to engraftment of neutrophils \>500/μl was defined as per Center for International Blood and Marrow Transplant Research (CIBMTR) standards, requiring donor chimerism for neutrophil engraftment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| First Grade 2/3 Bacterial or Invasive Fungal Infections by 100 Days Following Transplantation | 100 days post-transplant | First Bacterial Infection Grades 2-3 or Invasive Fungal Infection by 100 Days following Transplantation for the Intent to Treat Population |
| Days Alive and Out of Hospital in the First 100 Days Post-transplantation | 100 days post-transplantation | Days alive and out of hospital in the first 100 Days post-transplantation for the Intent to Treat Population |
| Number of Participants With Platelet Engraftment by 42 Days Post-transplantation | 42 days post-transplantation | Platelet engraftment defined as the first day of a minimum of three consecutive measurements on different days such that the patient has achieved a platelet count \> 20 × 10\^9/L with no platelet transfusions during the preceding seven days (counting day of engraftment as one of the preceding seven days) for the Intent to Treat Population |
Countries
Brazil, France, Israel, Italy, Netherlands, Portugal, Singapore, Spain, United Kingdom, United States
Contacts
STUDY_CHAIRMitchell Horwitz, MD
Duke University
Participant flow
Recruitment details
125 patients were screened, met inclusion criteria and were randomized to treatment from 33 transplant centers worldwide. First patient was consented on 20th December 2016 and the last patient consented on 27th December 2019.
Participants by arm
| Arm | Count |
|---|---|
| NiCord® (Omidubicel) NiCord® is a cryopreserved stem/progenitor cell based product comprised of:
1. ex vivo expanded, umbilical cord blood-derived hematopoietic CD34+ progenitor cells (NiCord® cultured fraction (CF))
2. the non-cultured cell fraction of the same Cord Blood Unit (CBU) (NiCord® Non-cultured Fraction (NF)) consisting of mature myeloid and lymphoid cells.
Both fractions, i.e. NiCord® CF and NiCord® NF, will be kept frozen until they are thawed and infused on the day of transplantation.
NiCord® (omidubicel) | 62 |
| Unmanipulated CBU(s) Unmanipulated cord blood unit(s) | 63 |
| Total | 125 |
Baseline characteristics
| Characteristic | NiCord® (Omidubicel) | Total | Unmanipulated CBU(s) |
|---|---|---|---|
| Age, Categorical <=18 years | 8 Participants | 14 Participants | 6 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 54 Participants | 111 Participants | 57 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 16 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 46 Participants | 98 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants | 11 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 17 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 20 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 11 Participants | 5 Participants |
| Race (NIH/OMB) White | 35 Participants | 72 Participants | 37 Participants |
| Region of Enrollment Brazil | 3 participants | 4 participants | 1 participants |
| Region of Enrollment Israel | 1 participants | 2 participants | 1 participants |
| Region of Enrollment Netherlands | 3 participants | 6 participants | 3 participants |
| Region of Enrollment Singapore | 4 participants | 9 participants | 5 participants |
| Region of Enrollment Spain | 8 participants | 15 participants | 7 participants |
| Region of Enrollment United Kingdom | 1 participants | 2 participants | 1 participants |
| Region of Enrollment United States | 42 participants | 87 participants | 45 participants |
| Sex: Female, Male Female | 30 Participants | 53 Participants | 23 Participants |
| Sex: Female, Male Male | 32 Participants | 72 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 19 / 52 | 24 / 56 |
| other Total, other adverse events | 52 / 52 | 56 / 56 |
| serious Total, serious adverse events | 47 / 52 | 51 / 56 |
Outcome results
Primary
Time to Neutrophil Engraftment
The time to engraftment of neutrophils \>500/μl was defined as per Center for International Blood and Marrow Transplant Research (CIBMTR) standards, requiring donor chimerism for neutrophil engraftment.
Time frame: post-transplant up to 42 days
Population: intent to treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NiCord® (Omidubicel) | Time to Neutrophil Engraftment | 12 days |
| Unmanipulated Cord Blood Unit(s) | Time to Neutrophil Engraftment | 22 days |
Secondary
Days Alive and Out of Hospital in the First 100 Days Post-transplantation
Days alive and out of hospital in the first 100 Days post-transplantation for the Intent to Treat Population
Time frame: 100 days post-transplantation
Population: Intent to Treat Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NiCord® (Omidubicel) | Days Alive and Out of Hospital in the First 100 Days Post-transplantation | 60.5 Days |
| Unmanipulated Cord Blood Unit(s) | Days Alive and Out of Hospital in the First 100 Days Post-transplantation | 48 Days |
Secondary
First Grade 2/3 Bacterial or Invasive Fungal Infections by 100 Days Following Transplantation
First Bacterial Infection Grades 2-3 or Invasive Fungal Infection by 100 Days following Transplantation for the Intent to Treat Population
Time frame: 100 days post-transplant
Population: Intent to Treat Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NiCord® (Omidubicel) | First Grade 2/3 Bacterial or Invasive Fungal Infections by 100 Days Following Transplantation | 24 Participants |
| Unmanipulated Cord Blood Unit(s) | First Grade 2/3 Bacterial or Invasive Fungal Infections by 100 Days Following Transplantation | 38 Participants |
Secondary
Number of Participants With Platelet Engraftment by 42 Days Post-transplantation
Platelet engraftment defined as the first day of a minimum of three consecutive measurements on different days such that the patient has achieved a platelet count \> 20 × 10\^9/L with no platelet transfusions during the preceding seven days (counting day of engraftment as one of the preceding seven days) for the Intent to Treat Population
Time frame: 42 days post-transplantation
Population: Intent to Treat Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NiCord® (Omidubicel) | Number of Participants With Platelet Engraftment by 42 Days Post-transplantation | 34 Participants |
| Unmanipulated Cord Blood Unit(s) | Number of Participants With Platelet Engraftment by 42 Days Post-transplantation | 22 Participants |