Transplantation of NiCord®, Umbilical Cord Blood-derived Ex Vivo Expanded Cells, in Patients With HM

Allogeneic Stem Cell Transplantation of NiCord®, Umbilical Cord Blood-derived Ex Vivo Expanded Stem and Progenitor Cells, in Adolescent and Adult Patients With Hematological Malignancies

A Study Evaluating the Safety and Efficacy of Transplantation of a single cord blood unit (CBU) of NiCord®, umbilical cord blood-derived Ex Vivo Expanded Stem and Progenitor Cells in Patients with Hematological Malignancies.

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 multi center, single arm study, evaluating the safety and efficacy of the transplantation of NiCord® to patients with hematological malignancies following myeloablative therapy. Total study duration is approximately 400 days from the signing of informed consent to the last visit one year following transplantation The overall study objective is to evaluate the safety and efficacy of NiCord®: single ex-vivo expanded cord blood unit transplantation in patients with hematological malignancies following myeloablative therapy as follows: The main study objectives are to assess the cumulative incidence of patients with NiCord®-derived neutrophil engraftment at 42 days following transplantation and to assess the incidence of secondary graft failure at 180 days following transplantation of NiCord® Ten evaluable patients recruited for the study should be 12-65 years of age, up to a maximum of 15 treated patients.

Hematological Malignancies, Acute Lymphoblastic Leukemia (ALL), Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS)

Assess the cumulative incidence of patients with NiCord®-derived neutrophil engraftment at 42 days following transplantation.

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 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

Horwitz ME, Wease S, Blackwell B, Valcarcel D, Frassoni F, Boelens JJ, Nierkens S, Jagasia M, Wagner JE, Kuball J, Koh LP, Majhail NS, Stiff PJ, Hanna R, Hwang WYK, Kurtzberg J, Cilloni D, Freedman LS, Montesinos P, Sanz G. Phase I/II Study of Stem-Cell Transplantation Using a Single Cord Blood Unit Expanded Ex Vivo With Nicotinamide. J Clin Oncol. 2019 Feb 10;37(5):367-374. doi: 10.1200/JCO.18.00053. Epub 2018 Dec 4.