Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Pilot Study Evaluating the Safety and Efficacy of a Co-Transplantation of NiCord®, a UCB-derived ex Vivo Expanded Population of Stem and Progenitor Cells with a Second, Unmanipulated CBU in Patients with Hematological Malignancies
Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative procedure for various hematological malignancies, bone marrow failure syndromes and inherited metabolic disorders. The application of allogeneic HSCT is limited by donor availability such that only approximately one-third of the otherwise appropriate candidates have suitably matched family donors. Alternative donors include mismatched family members or matched unrelated donors, but these approaches are often complicated by an increased risk of graft-versus-host disease (GvHD) and a prolonged and cumbersome search and procurement process. In addition, far fewer subjects of racial minorities find suitable human leukocyte antigen (HLA)-matched donors.
Umbilical cord blood has been increasingly used as an alternative source of stem cells and has extended the availability of allogeneic HSCT to patients who would otherwise not be eligible for this curative approach. In the last decade the number of cord blood transplantations from related and unrelated donors has increased dramatically. It is estimated that more than 20,000 patients have undergone cord blood transplantation from unrelated donors to date for a variety of genetic, hematological, immunological, metabolic and oncologic disorders. The major advantages of cord blood transplantation include easy procurement, no risk to donors, reduced incidence of transmitting infections, immediate availability, and reduced risk of acute GvHD in the setting of donor-recipient HLA mismatch. Nevertheless, the low cell dose remains a main limitation of this cell source leading to delayed hematopoietic reconstitution, higher risk of graft failure and relatively high treatment related mortality rates as compared to other hematopoeitic cell sources. To improve outcomes and extend applicability of cord blood transplantation, one potential solution is ex vivo expansion of cord blood-derived stem and progenitor cells.
The Sponsor has undertaken to develop NiCord®, which is based on a novel technology for 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 broader application of umbilical cord blood transplantation and improve clinical outcomes in subjects with high-risk hematological malignancies.
The main objective of the current study is to evaluate the safety of co-transplantation of NiCord® and an unmanipulated cord blood unit in patients with hematological malignancies following myeloablative therapy.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| NiCord | Experimental |
|
| 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 |
|---|---|---|
| Acute Toxicity Associated With the Infusion of NiCord | Acute toxicity associated with the infusion of NiCord will be measured by adverse events within 24 hours post-infusion, defined as the acute toxicity period. Known adverse events associated with myeloablation and cord blood transplant were specifically monitored including fever, chills, allergic reaction/hypersensitivity, anaphylaxis, sinus bradycardia, sinus tachycardia, hypertension, hypotension, nausea, vomiting, diarrhea, dyspnea, hypoxia, hemoglobinuria, infection, flank pain and any other skin, CNS, cardiac, pulmonary or other toxicity manifestations. | 180 days post-transplant |
| Proportion of Patients With Neutrophil Engraftment | Neutrophil engraftment was defined as achieving an Absolute Neutrophil Count (ANC) of ≥500 mm3 for 3 consecutive measurements on different days by day 42 inclusive (the day of engraftment was defined as the first of these 3 days). The ANC recovery must be of donor origin documented by peripheral blood chimerism assays indicating less than or equal to 10% host cells in peripheral blood. | 42 days |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Patients Who Developed Acute GvHD Grade II-IV and III-IV | Acute GvHD was assessed from transplantation (day 0) until day 99 post-transplant or more frequently as clinically indicated. GvHD was classified according to the Glucksberg Classification (Glucksberg, Storb et al. 1974). The overall grade of GvHD, however, was determined by an assessment of skin disease, liver disease and gastrointestinal manifestations. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| David Snyder, PhD | Gamida Cell ltd | Study Director |
| Joanne Kurtzberg, MD | Duke University | Principal Investigator |
| Mitchell Horwitz, MD | Duke University | Principal Investigator |
| Patrick Stiff, MD | Loyola University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Loyola University, Cardinal Bernardin Cancer Center | Maywood | Illinois | 60153 | United States | ||
| Duke University Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24911148 | Derived | Horwitz ME, Chao NJ, Rizzieri DA, Long GD, Sullivan KM, Gasparetto C, Chute JP, Morris A, McDonald C, Waters-Pick B, Stiff P, Wease S, Peled A, Snyder D, Cohen EG, Shoham H, Landau E, Friend E, Peleg I, Aschengrau D, Yackoubov D, Kurtzberg J, Peled T. Umbilical cord blood expansion with nicotinamide provides long-term multilineage engraftment. J Clin Invest. 2014 Jul;124(7):3121-8. doi: 10.1172/JCI74556. Epub 2014 Jun 9. | |
| 22198152 |
| Label | URL |
|---|---|
| Gamida Cell Ltd. | View source |
Not provided
12 patients were enrolled/transplanted; efficacy results were summarized for 11 patients treated with NiCord. 1 patient was transplanted with unmanipulated cord only. Safety results were summarized for all patients.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | NiCord | NiCord: NiCord is a cell-based product composed of umbilical cord-derived ex vivo expanded stem and progenitor cells. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| 180 days |
| Non-relapse Mortality | Proportion of patients who had non-relapse mortality at 100 days. | 100 days |
| Durham |
| North Carolina |
| 27705 |
| United States |
| Derived |
| Peled T, Shoham H, Aschengrau D, Yackoubov D, Frei G, Rosenheimer G N, Lerrer B, Cohen HY, Nagler A, Fibach E, Peled A. Nicotinamide, a SIRT1 inhibitor, inhibits differentiation and facilitates expansion of hematopoietic progenitor cells with enhanced bone marrow homing and engraftment. Exp Hematol. 2012 Apr;40(4):342-55.e1. doi: 10.1016/j.exphem.2011.12.005. Epub 2011 Dec 20. |
| Duke University Medical Center | View source |
| Loyola University | View source |
| COMPLETED | 1 patient received unmanipulated cord only. |
|
| NOT COMPLETED |
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | NiCord | NiCord®: NiCord® is a cell-based product composed of umbilical cord-derived ex vivo expanded stem and progenitor cells. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||||
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Count of Participants | 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 | Acute Toxicity Associated With the Infusion of NiCord | Acute toxicity associated with the infusion of NiCord will be measured by adverse events within 24 hours post-infusion, defined as the acute toxicity period. Known adverse events associated with myeloablation and cord blood transplant were specifically monitored including fever, chills, allergic reaction/hypersensitivity, anaphylaxis, sinus bradycardia, sinus tachycardia, hypertension, hypotension, nausea, vomiting, diarrhea, dyspnea, hypoxia, hemoglobinuria, infection, flank pain and any other skin, CNS, cardiac, pulmonary or other toxicity manifestations. | Patients transplanted with NiCord | Posted | Count of Participants | Participants | No | 180 days post-transplant |
|
|
| |||||||||||||||||||||||||
| Primary | Proportion of Patients With Neutrophil Engraftment | Neutrophil engraftment was defined as achieving an Absolute Neutrophil Count (ANC) of ≥500 mm3 for 3 consecutive measurements on different days by day 42 inclusive (the day of engraftment was defined as the first of these 3 days). The ANC recovery must be of donor origin documented by peripheral blood chimerism assays indicating less than or equal to 10% host cells in peripheral blood. | Patients transplanted with NiCord | Posted | Number | proportion of patients | 42 days |
|
| |||||||||||||||||||||||||||
| Secondary | Proportion of Patients Who Developed Acute GvHD Grade II-IV and III-IV | Acute GvHD was assessed from transplantation (day 0) until day 99 post-transplant or more frequently as clinically indicated. GvHD was classified according to the Glucksberg Classification (Glucksberg, Storb et al. 1974). The overall grade of GvHD, however, was determined by an assessment of skin disease, liver disease and gastrointestinal manifestations. | Posted | Number | proportion of patients | 180 days |
|
| ||||||||||||||||||||||||||||
| Secondary | Non-relapse Mortality | Proportion of patients who had non-relapse mortality at 100 days. | Posted | Number | proportion of patients | 100 days |
|
|
|
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | NiCord | NiCord®: NiCord® is a cell-based product composed of umbilical cord-derived ex vivo expanded stem and progenitor cells. | 3 | 12 | 8 | 12 | 11 | 12 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | Systematic Assessment |
| ||
| Gastrointestinal Disorder | Gastrointestinal disorders | Systematic Assessment |
| ||
| Depression | Psychiatric disorders | Systematic Assessment |
| ||
| Hypertension | Cardiac disorders | Systematic Assessment |
| ||
| Altered mental status | Psychiatric disorders | Systematic Assessment |
| ||
| Hemoptysis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Graft rejection | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Supraventricular tachycardia | Cardiac disorders | Systematic Assessment |
| ||
| Hematuria | Renal and urinary disorders | Systematic Assessment |
| ||
| Acute renal failure | Renal and urinary disorders | Systematic Assessment |
| ||
| Disease relapse | Investigations | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypertension | Cardiac disorders | Systematic Assessment |
| ||
| Hypomagnesemia | Investigations | Systematic Assessment |
| ||
| aGvHD | Immune system disorders | Systematic Assessment |
| ||
| CMV reactivation | Infections and infestations | Systematic Assessment |
| ||
| Nausea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Hypotension | Cardiac disorders | Systematic Assessment |
| ||
| Tachycardia | Cardiac disorders | Systematic Assessment |
| ||
| HHV-6 Reactivation | Infections and infestations | Systematic Assessment |
| ||
| Staph Coagulase Infection | Infections and infestations | Systematic Assessment |
| ||
| Hypocalcemia | Investigations | Systematic Assessment |
| ||
| BK virus infection | Infections and infestations | Systematic Assessment |
| ||
| Elevated LFTs | Gastrointestinal disorders | Systematic Assessment |
| ||
| E coli infection | Infections and infestations | Systematic Assessment |
| ||
| Hematuria | Renal and urinary disorders | Systematic Assessment |
| ||
| Sinus bradycardia | Cardiac disorders | Systematic Assessment |
| ||
| Proteinuria | Renal and urinary disorders | Systematic Assessment |
| ||
| Arrhythmia | Cardiac disorders | Systematic Assessment |
| ||
| RSV infection | Infections and infestations | Systematic Assessment |
| ||
| Pseudomonas infection | Infections and infestations | Systematic Assessment |
| ||
| Enterococcus infection | Infections and infestations | Systematic Assessment |
| ||
| CMV gastritis | Gastrointestinal disorders | Systematic Assessment |
| ||
| Hypoalbuminemia | Investigations | Systematic Assessment |
| ||
| Cystitis | Renal and urinary disorders | Systematic Assessment |
| ||
| Hypoxia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kelly Myers | Gamida Cell | +972-2-659-5631 | clinicaltrials@gamida-cell.com |
| ID | Term |
|---|---|
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| D015470 | Leukemia, Myeloid, Acute |
| D009190 | Myelodysplastic Syndromes |
| D008228 | Lymphoma, Non-Hodgkin |
| D006689 | Hodgkin Disease |
| D019337 | Hematologic Neoplasms |
| ID | Term |
|---|---|
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D007951 | Leukemia, Myeloid |
| D001855 | Bone Marrow Diseases |
| D008223 | Lymphoma |
| D009371 | Neoplasms by Site |
Not provided
Not provided
| >=65 years |
|
|
|
|