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Allogeneic SCT of NiCord®, UCB-Derived Ex Vivo Expanded Stem and Progenitor Cells, in Patients With Hemoglobinopathies

Phase 1
Completed
Conditions
Sickle Cell Disease & Thalassemia
Interventions
Registration Number
NCT01590628
Lead Sponsor
Gamida Cell ltd
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
16
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
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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
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
NiCordNiCordNiCord: NiCord® is a cell-based product composed of umbilical cord-derived ex vivo expanded stem and progenitor cells.
Primary Outcome Measures
NameTimeMethod
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 Outcome Measures
NameTimeMethod
Overall Survival180 days

Overall survival at 180 days

Proportion of Transplant-related Mortality.at 100 days

Transplant-related mortality is defined as death not preceded by autologous recovery.

Event-free Survival100 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.

Trial Locations

Locations (3)

The University Of Texas M. D. Anderson Cancer Center

🇺🇸

Houston, Texas, United States

Steven & Alexandra Cohen Children's Medical Center, New York

🇺🇸

New York, New York, United States

Duke University Medical Center

🇺🇸

Durham, North Carolina, United States

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