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Allogeneic Stem Cell Transplantation of NiCord®, Umbilical Cord Blood-Derived Ex Vivo Expanded Stem and Progenitor Cells, in Patients with Hemoglobinopathies
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| NiCord | Experimental | NiCord: NiCord® is a cell-based product composed of umbilical cord-derived ex vivo expanded stem and progenitor cells. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| NiCord | Drug | NiCord® is a cell-based product composed of umbilical cord-derived ex vivo expanded stem and progenitor cells |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 24 hours post-infusion |
| 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). | By Day 42 |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Transplant-related Mortality. | Transplant-related mortality is defined as death not preceded by autologous recovery. | at 100 days |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Joanne Kurtzberg, MD | Duke University Medical Center, NC, USA | Principal Investigator |
| Joel Brochstein, MD | Steven & Alexandra Cohen Children's Medical Center, New York | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Steven & Alexandra Cohen Children's Medical Center, New York | New York | New York | 11040 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33560399 | Derived | Parikh S, Brochstein JA, Galamidi E, Schwarzbach A, Kurtzberg J. Allogeneic stem cell transplantation with omidubicel in sickle cell disease. Blood Adv. 2021 Feb 9;5(3):843-852. doi: 10.1182/bloodadvances.2020003248. |
| Label | URL |
|---|---|
| Duke University Medical Center | View source |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | NiCord + Unmanipulated CBU | NiCord: NiCord® is a cell-based product composed of umbilical cord-derived ex vivo expanded stem and progenitor cells. NiCord was transplanted in Part 1 subjects, together with an unmanipulated CBU. |
| FG001 | NiCord | NiCord: NiCord® is a cell-based product composed of umbilical cord-derived ex vivo expanded stem and progenitor cells. NiCord was transplanted in Part 2 subjects as a standalone graft. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | NiCord |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Number | participants | 24 hours post-infusion |
|
|
adverse event data were collected throughout the post-transplant period (180 days) and 6 months post study completion (1 year post transplantation).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | NiCord + Unmanipulated CBU | NiCord: NiCord® is a cell-based product composed of umbilical cord-derived ex vivo expanded stem and progenitor cells. The primary safety objective was to assess the acute toxicity associated with the infusion of omidubicel within 24 hours post-infusion. Part 1: The primary efficacy objective of Part 1 was to assess the cumulative incidence of donor-derived neutrophil engraftment by Day 42 following co-transplantation of omidubicel and unmanipulated cord blood grafts. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anal fissure | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kelly Myers, CRA | Gamida Cell | 026595631 | kelly@gamida-cell.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 13, 2017 | May 19, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000755 | Anemia, Sickle Cell |
| D013789 | Thalassemia |
| D030342 | Genetic Diseases, Inborn |
| ID | Term |
|---|---|
| D000745 | Anemia, Hemolytic, Congenital |
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
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| 100 days post-transplant |
| Overall Survival | Overall survival at 180 days | 180 days |
| Duke University Medical Center |
| Durham |
| North Carolina |
| 27705 |
| United States |
| The University Of Texas M. D. Anderson Cancer Center | Houston | Texas | 77030-4009 | United States |
| Gamida Cell Ltd. | View source |
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.
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Sickle Cell or Thalassemia Disease Type | Count of Participants | Participants |
|
| CMV Screen (IgG or Total) (Segment S) positive | Count of Participants | Participants |
|
| Performance Status | The Karnofsky Performance Scale Index allows patients to be classified as to their functional impairment on a scale of 0 to 100%. This can be used to compare effectiveness of different therapies and to assess the prognosis in individual patients. The lower the Karnofsky score, the worse the survival for most serious illnesses. | Count of Participants | Participants |
|
| Disease characteristics | Number | participants |
|
| Hydroxyurea use prior to enrollment | Count of Participants | Participants |
|
| Counts |
|---|
| Participants |
|
|
| 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). | Posted | Count of Participants | Participants | By Day 42 |
|
|
|
| Secondary | Proportion of Transplant-related Mortality. | Transplant-related mortality is defined as death not preceded by autologous recovery. | Posted | Number | percentage of participants | at 100 days |
|
|
|
| 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. | 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. | Posted | Number | 95% Confidence Interval | percentage of participants | 100 days post-transplant |
|
|
|
| Secondary | Overall Survival | Overall survival at 180 days | 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. | Posted | Number | 95% Confidence Interval | percentage of participants | 180 days |
|
|
|
| 2 |
| 13 |
| 13 |
| 13 |
| 0 |
| 13 |
| EG001 | NiCord | NiCord: NiCord® is a cell-based product composed of umbilical cord-derived ex vivo expanded stem and progenitor cells. The primary safety objective was to assess the acute toxicity associated with the infusion of omidubicel within 24 hours post-infusion. Part 2: The primary efficacy objective of Part 2 was to assess the cumulative incidence of donor-derived neutrophil engraftment by Day 42 following transplantation of single unit omidubicel. | 0 | 3 | 3 | 3 | 0 | 3 |
| Nausea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Acute graft versus host disease | Immune system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Anaphylactic reaction | Immune system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Graft versus host disease | Immune system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Transplant rejection | Immune system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Bacteraemia | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Gastroenteritis adenovirus | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Pseudomonal bacteraemia | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Subdural haematoma | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
|
| Osteonecrosis | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Posterior reversible encephalopathy syndrome | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Seizure | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Hypovolaemic shock | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
|
| Venous thrombosis | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
|
| Renal Failure | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
|
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| D006425 |
| Hemic and Lymphatic Diseases |
| D006453 | Hemoglobinopathies |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |