Clinical trial NCT01590628: Allogeneic SCT of NiCord®, UCB-Derived Ex Vivo Expanded Stem and Progenitor Cells, in Patients With Hemoglobinopathies
Official title: Allogeneic Stem Cell Transplantation of NiCord®, Umbilical Cord Blood-Derived Ex Vivo Expanded Stem and Progenitor Cells, in Patients With Hemoglobinopathies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Sickle Cell Disease & Thalassemia
Keywords: Sickle Cell Disease & Thalassemia
Genetic disorder
Lead sponsor: Gamida Cell ltd
Sponsor class: INDUSTRY
First posted: 2012-05-03
Enrollment: 16
Sex: ALL
Minimum age (years): 2
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety and Tolerability Will be Measured by Acute NiCord® Infusional Toxicity.
timeFrame: 24 hours post-infusion
measure: Assessment of Cumulative Incidence of Donor-derived Neutrophil Engraftment.
timeFrame: By Day 42
Secondary outcomes:
measure: Proportion of Transplant-related Mortality.
timeFrame: at 100 days
measure: Event-free Survival
timeFrame: 100 days post-transplant
measure: Overall Survival
timeFrame: 180 days
Other outcomes:
Locations:
city: New York
country: United States
facility: Steven & Alexandra Cohen Children's Medical Center, New York
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Houston
country: United States
facility: The University Of Texas M. D. Anderson Cancer Center
state: Texas
Study officials:
affiliation: Duke University Medical Center, NC, USA
name: Joanne Kurtzberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Steven & Alexandra Cohen Children's Medical Center, New York
name: Joel Brochstein, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.