Clinical trial NCT02730299: Stem Cell Transplantation With NiCord® (Omidubicel) vs Standard UCB in Patients With Leukemia, Lymphoma, and MDS
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hematological Malignancies
Acute Lymphoblastic Leukemia (ALL)
Acute Myelogenous Leukemia (AML)
Chronic Myelogenous Leukemia (CML)
Myelodysplastic Syndrome (MDS)
Lymphoma
Acute Leukemia
Lead sponsor: Gamida Cell ltd
Sponsor class: INDUSTRY
First posted: 2016-04-06
Enrollment: 125
Sex: ALL
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Time to Neutrophil Engraftment
timeFrame: post-transplant up to 42 days
Secondary outcomes:
measure: First Grade 2/3 Bacterial or Invasive Fungal Infections by 100 Days Following Transplantation
timeFrame: 100 days post-transplant
measure: Days Alive and Out of Hospital in the First 100 Days Post-transplantation
timeFrame: 100 days post-transplantation
measure: Number of Participants With Platelet Engraftment by 42 Days Post-transplantation
timeFrame: 42 days post-transplantation
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Los Angeles
country: United States
facility: City of Hope
state: California
city: Palo Alto
country: United States
facility: Stanford University Cancer Institute
state: California
city: San Diego
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Denver
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Evanston
country: United States
facility: Northwestern University
state: Illinois
city: Maywood
country: United States
facility: Loyola University, Cardinal Bernardin Cancer Center
state: Illinois
city: Westwood
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Baltimore
country: United States
facility: The University of Maryland Medicine Center
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Medical Center
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Masonic Cancer Center
state: Minnesota
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Children's
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Pittsburgh
country: United States
facility: UPMC Children's Hospital of Pittsburgh
state: Pennsylvania
city: Germantown
country: United States
facility: West Cancer Clinic
state: Tennessee
city: Dallas
country: United States
facility: Children's Medical Center of Dallas
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Cancer Center
state: Virginia
city: Rio De Janeiro
country: Brazil
facility: Instituto Nacional de Câncer José Alencar Gomes da Silva - INCA
city: São Paulo
country: Brazil
facility: Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo Pediatrics
city: São Paulo
country: Brazil
facility: Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
city: São Paulo
country: Brazil
facility: Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo
city: São Paulo
country: Brazil
facility: Hospital Israelita Albert Einstein
city: Paris
country: France
facility: Robert Debré
city: Haifa
country: Israel
facility: Rambam
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Petach Tikva
country: Israel
facility: Rabin Medical Center, Beilinson Hospital
city: Tel Aviv
country: Israel
facility: Dana-Dwek Children's Hospital, Tel-Aviv Sourasky Medical Center
city: Tel Aviv
country: Israel
facility: Tel-Aviv Sourasky Medical Center
city: Tel HaShomer
country: Israel
facility: Chaim Sheba Medical Center, The Edmond and Lily Safra Children's hospital
city: Florence
country: Italy
facility: Careggi University Hospital
city: Rome
country: Italy
facility: Ospedale Pediatrico Bambino Gesù
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Utrecht
country: Netherlands
facility: Prinses Maxima Centrum voor Kinderoncologie B.V.
city: Lisbon
country: Portugal
facility: Instituto Português de Oncologia de Lisboa Francisco Gentil
city: Singapore
country: Singapore
facility: National University Cancer Institute
city: Singapore
country: Singapore
facility: Singapore General Hospital
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron pediatrics
city: Barcelona
country: Spain
facility: University Hospital Vall d'Hebron
city: Barcelona
country: Spain
facility: ICO Bellvitge
city: Barcelona
country: Spain
facility: Sant Joan de Deu
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico La Fe (pediatric)
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
state: Surrey
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Leeds
country: United Kingdom
facility: St James Hospital
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust
Study officials:
affiliation: Duke University
name: Mitchell Horwitz, MD
role: STUDY_CHAIR
References:
citation: Horwitz ME, Stiff PJ, Cutler C, Brunstein C, Hanna R, Maziarz RT, Rezvani AR, Karris NA, McGuirk J, Valcarcel D, Schiller GJ, Lindemans CA, Hwang WYK, Koh LP, Keating A, Khaled Y, Hamerschlak N, Frankfurt O, Peled T, Segalovich I, Blackwell B, Wease S, Freedman LS, Galamidi-Cohen E, Sanz G. Omidubicel vs standard myeloablative umbilical cord blood transplantation: results of a phase 3 randomized study. Blood. 2021 Oct 21;138(16):1429-1440. doi: 10.1182/blood.2021011719.
citation: Del Pozo Martin Y. 47th Annual Meeting of the EBMT. Lancet Haematol. 2021 May;8(5):e317-e318. doi: 10.1016/S2352-3026(21)00104-6. Epub 2021 Mar 31. No abstract available.