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

Phase 3
Completed
Conditions
Hematological Malignancies
Acute Lymphoblastic Leukemia (ALL)
Acute Myelogenous Leukemia (AML)
Myelodysplastic Syndrome (MDS)
Lymphoma
Chronic Myelogenous Leukemia (CML)
Acute Leukemia
Interventions
Other: Cord Blood Unit
Registration Number
NCT02730299
Lead Sponsor
Gamida Cell ltd
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
125
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
NiCord® (omidubicel)NiCord® (omidubicel)NiCord® is a cryopreserved stem/progenitor cell based product comprised of: 1. ex vivo expanded, umbilical cord blood-derived hematopoietic CD34+ progenitor cells (NiCord® cultured fraction (CF)) 2. 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.
Unmanipulated CBU(s)Cord Blood Unit-
Primary Outcome Measures
NameTimeMethod
Time to Neutrophil Engraftmentpost-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 Outcome Measures
NameTimeMethod
Days Alive and Out of Hospital in the First 100 Days Post-transplantation100 days post-transplantation

Days alive and out of hospital in the first 100 Days post-transplantation for the Intent to Treat Population

Number of Participants With Platelet Engraftment by 42 Days Post-transplantation42 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

First Grade 2/3 Bacterial or Invasive Fungal Infections by 100 Days Following Transplantation100 days post-transplant

First Bacterial Infection Grades 2-3 or Invasive Fungal Infection by 100 Days following Transplantation for the Intent to Treat Population

Trial Locations

Locations (52)

UCLA

🇺🇸

Los Angeles, California, United States

City of Hope

🇺🇸

Los Angeles, California, United States

Stanford University Cancer Institute

🇺🇸

Palo Alto, California, United States

UC San Diego Moores Cancer Center

🇺🇸

San Diego, California, United States

Children's Hospital Colorado

🇺🇸

Denver, Colorado, United States

Northwestern University

🇺🇸

Evanston, Illinois, United States

Loyola University, Cardinal Bernardin Cancer Center

🇺🇸

Maywood, Illinois, United States

University of Kansas Cancer Center

🇺🇸

Westwood, Kansas, United States

The University of Maryland Medicine Center

🇺🇸

Baltimore, Maryland, United States

Boston Children's Hospital

🇺🇸

Boston, Massachusetts, United States

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UCLA
🇺🇸Los Angeles, California, United States
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