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

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02730299
• Other study ID #: GC P#05.01.020
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 16, 2016
• Est. completion date: February 18, 2025

Study information

• Verified date: July 2023
• Source: Gamida Cell ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 125
• Est. completion date: February 18, 2025
• Est. primary completion date: April 29, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Leukemia
• Acute Lymphoblastic Leukemia (ALL)
• Acute Myelogenous Leukemia (AML)
• Chronic Myelogenous Leukemia (CML)
• Hematologic Neoplasms
• Hematological Malignancies
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Lymphoma
• Myelodysplastic Syndrome (MDS)
• Myelodysplastic Syndromes
• Neoplasms
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia

Intervention

Drug:
• NiCord® (omidubicel)

Other:
• Cord Blood Unit
Cord blood unit

Locations

Country	Name	City	State
Brazil	Instituto Nacional de Câncer José Alencar Gomes da Silva - INCA	Rio De Janeiro
Brazil	Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo	São Paulo
Brazil	Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo Pediatrics	São Paulo
Brazil	Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo	São Paulo
Brazil	Hospital Israelita Albert Einstein	São Paulo
France	Robert Debré	Paris
Israel	Rambam	Haifa
Israel	Hadassah Medical Center	Jerusalem
Israel	Rabin Medical Center, Beilinson Hospital	Petach Tikva
Israel	Dana-Dwek Children's Hospital, Tel-Aviv Sourasky Medical Center	Tel Aviv
Israel	Tel-Aviv Sourasky Medical Center	Tel Aviv
Israel	Chaim Sheba Medical Center, The Edmond and Lily Safra Children's hospital	Tel HaShomer
Italy	Careggi University Hospital	Florence
Italy	Ospedale Pediatrico Bambino Gesù	Rome
Netherlands	Prinses Maxima Centrum voor Kinderoncologie B.V.	Utrecht
Netherlands	University Medical Center Utrecht	Utrecht
Portugal	Instituto Português de Oncologia de Lisboa Francisco Gentil	Lisbon
Singapore	National University Cancer Institute	Singapore
Singapore	Singapore General Hospital	Singapore
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitari Vall d'Hebron pediatrics	Barcelona
Spain	ICO Bellvitge	Barcelona
Spain	Sant Joan de Deu	Barcelona
Spain	University Hospital Vall d'Hebron	Barcelona
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Hospital Universitario La Fe	Valencia
Spain	Hospital Universitario y Politécnico La Fe (pediatric)	Valencia
United Kingdom	Queen Elizabeth Hospital	Birmingham
United Kingdom	St James Hospital	Leeds
United Kingdom	Manchester University NHS Foundation Trust	Manchester
United Kingdom	The Royal Marsden NHS Foundation Trust	Sutton	Surrey
United States	The University of Maryland Medicine Center	Baltimore	Maryland
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	Cleveland Clinic Children's	Cleveland	Ohio
United States	Children's Medical Center of Dallas	Dallas	Texas
United States	Children's Hospital Colorado	Denver	Colorado
United States	Henry Ford Medical Center	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Northwestern University	Evanston	Illinois
United States	West Cancer Clinic	Germantown	Tennessee
United States	City of Hope	Los Angeles	California
United States	UCLA	Los Angeles	California
United States	Loyola University, Cardinal Bernardin Cancer Center	Maywood	Illinois
United States	University of Minnesota Masonic Cancer Center	Minneapolis	Minnesota
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Stanford University Cancer Institute	Palo Alto	California
United States	UPMC Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	UC San Diego Moores Cancer Center	San Diego	California
United States	University of Kansas Cancer Center	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Gamida Cell ltd

Countries where clinical trial is conducted

United States,  Brazil,  France,  Israel,  Italy,  Netherlands,  Portugal,  Singapore,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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