Stem Cell Transplantation With NiCord® (Omidubicel) vs Standard UCB in Patients With Leukemia, Lymphoma, and MDS

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Hematological Malignancies, Acute Lymphoblastic Leukemia (ALL), Acute Myelogenous Leukemia (AML), Chronic Myelogenous Leukemia (CML), Myelodysplastic Syndrome (MDS), Lymphoma, Acute Leukemia

Intervention / Treatment
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* Drug: NiCord® (omidubicel)
* Other: Cord Blood Unit


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NiCord® (omidubicel)<br>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. | Drug: NiCord® (omidubicel)<br> <br> |
| Active Comparator: Unmanipulated CBU(s)<br> | Other: Cord Blood Unit<br>* Cord blood unit<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Neutrophil Engraftment | 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. | post-transplant up to 42 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| First Grade 2/3 Bacterial or Invasive Fungal Infections by 100 Days Following Transplantation | First Bacterial Infection Grades 2-3 or Invasive Fungal Infection by 100 Days following Transplantation for the Intent to Treat Population | 100 days post-transplant | 
| Days Alive and Out of Hospital in the First 100 Days Post-transplantation | Days alive and out of hospital in the first 100 Days post-transplantation for the Intent to Treat Population | 100 days post-transplantation | 
| Number of Participants With Platelet Engraftment by 42 Days Post-transplantation | Platelet engraftment defined as the first day of a minimum of three consecutive measurements on different days such that the patient has achieved a platelet count > 20 × 10^9/L with no platelet transfusions during the preceding seven days (counting day of engraftment as one of the preceding seven days) for the Intent to Treat Population | 42 days post-transplantation |