A Multicenter, Randomized, Phase III Registration Trial of Transplantation of NiCord®, Ex Vivo Expanded, UCB-derived, Stem and Progenitor Cells, vs. Unmanipulated UCB for Patients With Hematological Malignancies
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Gamida Cell ltd
- Enrollment
- 125
- Locations
- 52
- Primary Endpoint
- Time to Neutrophil Engraftment
Study Overview
Brief Summary
This study is an open-label, controlled, multicenter, international, Phase III, randomized study of transplantation of NiCord® versus transplantation of one or two unmanipulated, unrelated cord blood units in patients with acute lymphoblastic leukemia or acute myeloid leukemia, myelodysplastic syndrome, chronic myeloid leukemia or lymphoma, all with required disease features rendering them eligible for allogeneic transplantation.
Detailed Description
Successful blood and marrow transplantation (BMT) requires the infusion of a sufficient number of hematopoietic stem/progenitor cells (HSPCs), capable of both homing to the bone marrow and regenerating a full array of hematopoietic cell lineages with early and late repopulating ability in a timely fashion.
A major drawback of Umbilical Cord Blood (UCB) is the low stem cell dose available for transplantation, compared to mobilized peripheral blood (PB) or bone marrow. This low stem cell dose can compromise the chances of engraftment and contributes to delayed kinetics of neutrophil and platelet recovery, as well as other transplant outcomes.
The aim of ex vivo expansion of cord blood is to provide a graft with sufficient numbers of cells that have rapid and robust in vivo neutrophil and platelet producing potential to enable successful transplantation.
NiCord® is a stem/progenitor cell-based product composed of ex vivo expanded allogeneic cells from one entire unit of UCB. NiCord® utilizes the small molecule nicotinamide (NAM), as an epigenetic approach to inhibit differentiation and to increase the migration, bone marrow (BM) homing and engraftment efficiency of Hematopoietic Progenitor Cells (HPC) expanded in ex vivo cultures. The chief aim of the study is to compare the safety and efficacy of NiCord® single ex-vivo expanded cord blood unit transplantation to unmanipulated cord blood unit transplantation in patients with hematological malignancies following conditioning therapy.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 12 Years to 65 Years (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Applicable disease criteria
- •Patients must have one or two partially HLA-matched CBUs
- •Back-up stem cell source
- •Adequate Karnofsky/Lansky Performance score
- •Sufficient physiological reserves
- •Signed written informed consent
Exclusion Criteria
- •HLA-matched donor able to donate
- •Prior allogeneic HSCT
- •Other active malignancy
- •Active or uncontrolled infection
- •Active/symptoms of central nervous system (CNS) disease
- •Pregnancy or lactation
Arms & Interventions
Unmanipulated CBU(s)
Intervention: Cord Blood Unit (Other)
NiCord® (omidubicel)
NiCord® is a cryopreserved stem/progenitor cell based product comprised of:
- ex vivo expanded, umbilical cord blood-derived hematopoietic CD34+ progenitor cells (NiCord® cultured fraction (CF))
- the non-cultured cell fraction of the same Cord Blood Unit (CBU) (NiCord® Non-cultured Fraction (NF)) consisting of mature myeloid and lymphoid cells.
Both fractions, i.e. NiCord® CF and NiCord® NF, will be kept frozen until they are thawed and infused on the day of transplantation.
Intervention: NiCord® (omidubicel) (Drug)
Outcomes
Primary Outcomes
Time to Neutrophil Engraftment
Time Frame: post-transplant up to 42 days
The time to engraftment of neutrophils \>500/μl was defined as per Center for International Blood and Marrow Transplant Research (CIBMTR) standards, requiring donor chimerism for neutrophil engraftment.
Secondary Outcomes
- Days Alive and Out of Hospital in the First 100 Days Post-transplantation(100 days post-transplantation)
- Number of Participants With Platelet Engraftment by 42 Days Post-transplantation(42 days post-transplantation)
- First Grade 2/3 Bacterial or Invasive Fungal Infections by 100 Days Following Transplantation(100 days post-transplant)