Sickle Cell Disease & Thalassemia
Conditions
Keywords
Sickle Cell Disease & Thalassemia, Genetic disorder
Brief summary
Allogeneic Stem Cell Transplantation of NiCord®, Umbilical Cord Blood-Derived Ex Vivo Expanded Stem and Progenitor Cells, in Patients with Hemoglobinopathies
Detailed description
Umbilical cord blood (UCB) is an alternative stem cell source for hematopoietic stem cell transplantations (HSCT) and can be used for the treatment of various life-threatening diseases, such as hematological malignancies or genetic blood disorders, in such cases where a matched related stem cell donor is not available. However, the major drawback of using this valuable stem cells source is the limited cell dose in a single cord blood unit (CBU), which was shown to be associated with inadequate hematopoietic reconstitution and high risk of transplant-related mortality. To improve outcomes and extend applicability of UCB transplantation, one potential solution is ex vivo expansion of UCB-derived stem and progenitor cells. NiCord® is a stem/progenitor cell based product composed of ex vivo expanded allogeneic UCB cells. NiCord® is based on a novel technology for the ex vivo cell expansion of cord blood derived hematopoietic progenitor cells. By increasing the number of the short and long-term reconstitution progenitor cells transplanted, NiCord® has the potential to enable the broader application of UCB transplantation, and improve the clinical outcomes of UCB transplantation. In Part 1 of this study, NiCord® will be administered to the patient in conjunction with a second, unmanipulated CBU. In Part 2 of this study, NiCord® will be administered to the patient without a second, unmanipulated CBU. The study duration per patient is approximately 270 days from signing of informed consent to last visit on day 180 post-transplant. The overall study objectives of part 1 of this study are to evaluate the safety and efficacy of co-transplantation of NiCord® and an unmanipulated CBU in patients with Hemoglobinopathies (Sickle Cell Disease (SCD), or thalassemia major) following myeloablative therapy. The overall study objectives of part 2 of this study are to evaluate the safety and efficacy of transplantation of NiCord® in patients with Hemoglobinopathies (Sickle Cell Disease (SCD), or thalassemia major) following myeloablative therapy. The study hypothesis for part 1 of this study is that the co-transplantation of NiCord® and an unmanipulated unrelated cord blood graft in patients with hemoglobinopathies (SCD, or thalassemia major) following myeloablative preparative therapy will be safe and will enable cord blood engraftment. The study hypothesis for part 2 of this study is that transplantation of NiCord® in patients with hemoglobinopathies (SCD, or thalassemia major) following myeloablative preparative therapy will be safe and will enable cord blood engraftment. Up to fifteen (15) evaluable patients recruited for part 1 of the study and up to five (5) patients for part 2 of the study should be 2-45 years of age, at least 10 kg in weight, have symptomatic SCD or thalassemia major and should be considered as candidates for allogeneic myeloablative HSCT for the treatment of SCD.
Interventions
DRUGNiCord
NiCord® is a cell-based product composed of umbilical cord-derived ex vivo expanded stem and progenitor cells
Sponsors
Gamida Cell ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Must be 2 - 45 years of age and at least 10 kg * Must have clinically severe SCD (SS, SC or SBeta0 Thal) or thalassemia major and be eligible for myeloablative SCT * Must have two partially HLA-matched CBUs for part 1; and one partially HLA-matched CBU for part 2 * Back-up autologous stem cells harvested from bone marrow * Adequate Karnofsky Performance score or Lansky Play-Performance scale * Sufficient physiological reserves * Signed written informed consent
Exclusion criteria
* HLA-matched related donor able to donate * Severe alloimmunization with inability to guarantee a supply of adequate PRBC donors * Prior allogeneic hematopoietic SCT within the last 12 months or reduced-intensity transplant within the past 6 months * Human immunodeficiency virus (HIV) infection * Active or uncontrolled infection * Pregnancy or lactation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability Will be Measured by Acute NiCord® Infusional Toxicity. | 24 hours post-infusion | Assessment of acute toxicity associated with the infusion of NiCord within 24 hours post-infusion. |
| Assessment of Cumulative Incidence of Donor-derived Neutrophil Engraftment. | By Day 42 | Neutrophil engraftment is defined as achieving an absolute neutrophil count (ANC) of ≥500/ μL for 3 consecutive measurements on different days by Day 42 inclusive (the day of engraftment was defined as the first of these 3 days). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Transplant-related Mortality. | at 100 days | Transplant-related mortality is defined as death not preceded by autologous recovery. |
| Event-free Survival | 100 days post-transplant | Patients with event-free survival at 100 days post-transplant that did not have one of the following events: death, autologous recovery, primary or secondary graft failure. |
| Overall Survival | 180 days | Overall survival at 180 days |
Countries
United States
Participant flow
Recruitment details
The study enrolled and treated 16 patients in total. 13 patients were treated with omidubicel and an unmanipulated CBU and these served as the primary analysis population for all study endpoints. Three additional patients who were exposed to omidubicel as a single graft source, were included in the safety summaries in order to encompass the entire population exposed to omidubicel.
Participants by arm
| Arm | Count |
|---|---|
| NiCord + Unmanipulated CBU NiCord: NiCord® is a cell-based product composed of umbilical cord-derived ex vivo expanded stem and progenitor cells.
The NiCord was transplanted together with an unmanipulated CBU graft. | 13 |
| NiCord NiCord: NiCord® is a cell-based product composed of umbilical cord-derived ex vivo expanded stem and progenitor cells.
The NiCord was transplanted as a standalone product. | 3 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 2 | 0 |
Baseline characteristics
| Characteristic | NiCord + Unmanipulated CBU | NiCord | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 13 Participants | 3 Participants | 16 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| CMV Screen (IgG or Total) (Segment S) positive | 7 Participants | 2 Participants | 9 Participants |
| Disease characteristics Abnormal MRI/MRA | 5 participants | 1 participants | 6 participants |
| Disease characteristics Acute Chest Syndrome (Two or More Episodes in the Past 2 Years) | 2 participants | 0 participants | 2 participants |
| Disease characteristics chronic PRBC transfusion therapy | 0 participants | 0 participants | 0 participants |
| Disease characteristics Patient has undergone TCD velocity tests | 1 participants | 0 participants | 1 participants |
| Disease characteristics SCD-related & clinically significant neurologic event | 4 participants | 1 participants | 5 participants |
| Disease characteristics Three or More Recurrent Painful Events in the Past 2 Years | 6 participants | 2 participants | 8 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 3 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Hydroxyurea use prior to enrollment | 10 Participants | 2 Participants | 12 Participants |
| Performance Status 100 | 6 Participants | 2 Participants | 8 Participants |
| Performance Status 70 | 0 Participants | 1 Participants | 1 Participants |
| Performance Status 80 | 4 Participants | 0 Participants | 4 Participants |
| Performance Status 90 | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 3 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 13 Participants | 3 Participants | 16 Participants |
| Sex: Female, Male Female | 9 Participants | 1 Participants | 10 Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 6 Participants |
| Sickle Cell or Thalassemia Disease Type Alpha Thal Major | 0 Participants | 0 Participants | 0 Participants |
| Sickle Cell or Thalassemia Disease Type Beta Thal Major | 0 Participants | 0 Participants | 0 Participants |
| Sickle Cell or Thalassemia Disease Type Hb SBeta0 Thal | 0 Participants | 1 Participants | 1 Participants |
| Sickle Cell or Thalassemia Disease Type Hb SC | 0 Participants | 0 Participants | 0 Participants |
| Sickle Cell or Thalassemia Disease Type Hb SD | 0 Participants | 0 Participants | 0 Participants |
| Sickle Cell or Thalassemia Disease Type Hb SOarab | 0 Participants | 0 Participants | 0 Participants |
| Sickle Cell or Thalassemia Disease Type Hb SS | 13 Participants | 2 Participants | 15 Participants |
| Sickle Cell or Thalassemia Disease Type Other SCD Type | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 13 | 0 / 3 |
| other Total, other adverse events | 0 / 13 | 0 / 3 |
| serious Total, serious adverse events | 13 / 13 | 3 / 3 |
Outcome results
Primary
Assessment of Cumulative Incidence of Donor-derived Neutrophil Engraftment.
Neutrophil engraftment is defined as achieving an absolute neutrophil count (ANC) of ≥500/ μL for 3 consecutive measurements on different days by Day 42 inclusive (the day of engraftment was defined as the first of these 3 days).
Time frame: By Day 42
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NiCord + Unmanipulated CBU | Assessment of Cumulative Incidence of Donor-derived Neutrophil Engraftment. | 13 Participants |
| NiCord | Assessment of Cumulative Incidence of Donor-derived Neutrophil Engraftment. | 3 Participants |
Primary
Safety and Tolerability Will be Measured by Acute NiCord® Infusional Toxicity.
Assessment of acute toxicity associated with the infusion of NiCord within 24 hours post-infusion.
Time frame: 24 hours post-infusion
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NiCord + Unmanipulated CBU | Safety and Tolerability Will be Measured by Acute NiCord® Infusional Toxicity. | Grade 4-5 acute toxicity event | 0 participants |
| NiCord + Unmanipulated CBU | Safety and Tolerability Will be Measured by Acute NiCord® Infusional Toxicity. | Grade 3 acute toxicity event | 3 participants |
| NiCord | Safety and Tolerability Will be Measured by Acute NiCord® Infusional Toxicity. | Grade 4-5 acute toxicity event | 0 participants |
| NiCord | Safety and Tolerability Will be Measured by Acute NiCord® Infusional Toxicity. | Grade 3 acute toxicity event | 0 participants |
Secondary
Event-free Survival
Patients with event-free survival at 100 days post-transplant that did not have one of the following events: death, autologous recovery, primary or secondary graft failure.
Time frame: 100 days post-transplant
Population: In the first group, 13 patients received NiCord together with a second unmanipulated CBU. In the 2nd group, 3 patients received NiCord as a standalone graft. No statistical analysis was performed for this outcome as this number of patients is too small for analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NiCord + Unmanipulated CBU | Event-free Survival | 92.3 percentage of participants |
| NiCord | Event-free Survival | 66.6 percentage of participants |
Secondary
Overall Survival
Overall survival at 180 days
Time frame: 180 days
Population: In the first group, 13 patients received NiCord together with a second unmanipulated CBU. In the 2nd group, 3 patients received NiCord as a standalone graft.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NiCord + Unmanipulated CBU | Overall Survival | 92.3 percentage of participants |
| NiCord | Overall Survival | 100 percentage of participants |
Secondary
Proportion of Transplant-related Mortality.
Transplant-related mortality is defined as death not preceded by autologous recovery.
Time frame: at 100 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NiCord + Unmanipulated CBU | Proportion of Transplant-related Mortality. | 0 percentage of participants |
| NiCord | Proportion of Transplant-related Mortality. | 0 percentage of participants |