Pilot Study Evaluating Safety & Efficacy of a DCBT: NiCord® & UNM CBU to SCD Patients After Myeloablative Therapy

• Safety and Tolerability will be measured by acute NiCord® infusional toxicity. [ Time Frame: 24 hours post-infusion ] [ Designated as safety issue: Yes ]
• Assessment of cumulative incidence of donor-derived neutrophil engraftment. [ Time Frame: By Day 42 ] [ Designated as safety issue: Yes ]

• Proportion of transplant-related mortality. [ Time Frame: at 100 days ] [ Designated as safety issue: Yes ]
• Event-free survival. [ Time Frame: at 100 days ] [ Designated as safety issue: Yes ]
• Overall survival. [ Time Frame: at 180 days. ] [ Designated as safety issue: Yes ]

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 and a Second, Unmanipulated CBU in Patients with Sickle Cell Disease (SCD).

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.

The study is designed as a pilot, single center, single arm study, evaluating the safety and efficacy of the co-transplantation of NiCord® with an unmanipulated CBU to patients with SCD following myeloablative therapy.

The total study duration is approximately 220 days, starting with the signing of an informed consent to the last visit on day 180 post-transplant. A long-term post-study follow-up is planned at 6 months post-study completion (1 year post-transplantation), and a long-term follow-up using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry.

The study hypothesis is that the co-transplantation of NiCord® and an unmanipulated unrelated cord blood graft in patients with SCD following myeloablative preparative therapy consisting of hydroxyurea, busulfan, cyclophosphamide and ATG will be safe and will enable cord blood engraftment.

The main study objectives are assessment of the acute toxicity associated with the infusion of NiCord® within 24 hours post infusion, and assessment of cumulative incidence of donor-derived neutrophil engraftment by day 42 following co-transplantation of NiCord® and unmanipulated cord blood grafts. In addition, the proportion of transplant-related mortality at 100 days, event-free survival at 100 days and overall survival at 180 days will be assessed.

Ten evaluable patients recruited for the study should be 2-21 years of age, at least 10 kg in weight, have symptomatic SCD and should be considered as candidates for allogeneic myeloablative HSCT for the treatment of SCD.

Inclusion Criteria:

• Must be 2 - 21 years of age and at least 10 kg
• Must have clinically severe SCD (SS, SC or SBeta0 Thal) and eligible for myeloablative SCT
• Must have two partially HLA-matched CBUs
• 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