Acute Lymphoblastic Leukemia (ALL), Acute Myelogenous Leukemia (AML), Hodgkin's Disease, Myelodysplastic Syndrome (MDS), Non-Hodgkin's Lymphoma
Conditions
Keywords
Double Umbilical Cord Blood Stem Cell Transplantation, Hematological Malignancies, HLA Mismatched Donors, Cord Blood Transplantation
Brief summary
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
Detailed description
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.
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
8 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Applicable disease and eligible for myeloablative SCT * Patients must have two partially HLA-matched CBUs * Back-up stem cell source * 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 * Prior allogeneic HSCT * Lymphoma patients with progressive disease * Other active malignancy * Human immunodeficiency virus (HIV) infection * Active or uncontrolled infection * Active/symptoms of central nervous system (CNS) disease * Pregnancy or lactation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Acute Toxicity Associated With the Infusion of NiCord | 180 days post-transplant | 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. |
| Proportion of Patients With Neutrophil Engraftment | 42 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Who Developed Acute GvHD Grade II-IV and III-IV | 180 days | 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. |
| Non-relapse Mortality | 100 days | Proportion of patients who had non-relapse mortality at 100 days. |
Countries
United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| NiCord NiCord®: NiCord® is a cell-based product composed of umbilical cord-derived ex vivo expanded stem and progenitor cells. | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | NiCord |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 45 years |
| Region of Enrollment United States | 12 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 12 |
| other Total, other adverse events | 11 / 12 |
| serious Total, serious adverse events | 8 / 12 |
Outcome results
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.
Time frame: 180 days post-transplant
Population: Patients transplanted with NiCord
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NiCord | Acute Toxicity Associated With the Infusion of NiCord | 0 Participants |
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.
Time frame: 42 days
Population: Patients transplanted with NiCord
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NiCord | Proportion of Patients With Neutrophil Engraftment | 0.91 proportion of patients |
Secondary
Non-relapse Mortality
Proportion of patients who had non-relapse mortality at 100 days.
Time frame: 100 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NiCord | Non-relapse Mortality | 0.09 proportion of patients |
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.
Time frame: 180 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NiCord | Proportion of Patients Who Developed Acute GvHD Grade II-IV and III-IV | 0.45 proportion of patients |
| Grade III-IV GvHD | Proportion of Patients Who Developed Acute GvHD Grade II-IV and III-IV | 0 proportion of patients |