Clinical trial NCT01221857: Pilot Study Evaluating Safety & Efficacy of DCBT: NiCord® & UNM CBU to Patients With Hematological Malignancies
Official title: Allogeneic Stem Cell Transplantation of NiCord®, Umbilical Cord Blood-Derived Ex Vivo Expanded Stem and Progenitor Cells, in Combination With a Second, Unmanipulated Cord Blood Unit in Patients With Hematological Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Acute Lymphoblastic Leukemia (ALL)
Acute Myelogenous Leukemia (AML)
Myelodysplastic Syndrome (MDS)
Non-Hodgkin's Lymphoma
Hodgkin's Disease
Keywords: Double Umbilical Cord Blood Stem Cell Transplantation
Hematological Malignancies
HLA Mismatched Donors
Cord Blood Transplantation
Lead sponsor: Gamida Cell ltd
Sponsor class: INDUSTRY
First posted: 2010-10-15
Enrollment: 12
Sex: ALL
Minimum age (years): 8
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Pilot Study Evaluating the Safety and Efficacy of a Co-Transplantation of NiCord®, a UCB-derived ex Vivo Expanded Population of Stem and Progenitor Cells with a Second, Unmanipulated CBU in Patients with Hematological Malignancies

Detailed description: Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative procedure for various hematological malignancies, bone marrow failure syndromes and inherited metabolic disorders. The application of allogeneic HSCT is limited by donor availability such that only approximately one-third of the otherwise appropriate candidates have suitably matched family donors. Alternative donors include mismatched family members or matched unrelated donors, but these approaches are often complicated by an increased risk of graft-versus-host disease (GvHD) and a prolonged and cumbersome search and procurement process. In addition, far fewer subjects of racial minorities find suitable human leukocyte antigen (HLA)-matched donors.

Umbilical cord blood has been increasingly used as an alternative source of stem cells and has extended the availability of allogeneic HSCT to patients who would otherwise not be eligible for this curative approach. In the last decade the number of cord blood transplantations from related and unrelated donors has increased dramatically. It is estimated that more than 20,000 patients have undergone cord blood transplantation from unrelated donors to date for a variety of genetic, hematological, immunological, metabolic and oncologic disorders. The major advantages of cord blood transplantation include easy procurement, no risk to donors, reduced incidence of transmitting infections, immediate availability, and reduced risk of acute GvHD in the setting of donor-recipient HLA mismatch. Nevertheless, the low cell dose remains a main limitation of this cell source leading to delayed hematopoietic reconstitution, higher risk of graft failure and relatively high treatment related mortality rates as compared to other hematopoeitic cell sources. To improve outcomes and extend applicability of cord blood transplantation, one potential solution is ex vivo expansion of cord blood-derived stem and progenitor cells.

The Sponsor has undertaken to develop NiCord®, which is based on a novel technology for 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 broader application of umbilical cord blood transplantation and improve clinical outcomes in subjects with high-risk hematological malignancies.

The main objective of the current study is to evaluate the safety of co-transplantation of NiCord® and an unmanipulated cord blood unit in patients with hematological malignancies following myeloablative therapy.

Eligibility criteria: 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 related donor able to donate
* Prior allogeneic HSCT
* Lymphoma patients with progressive disease
* Other active malignancy
* Human immunodeficiency virus (HIV) infection
* Active or uncontrolled infection
* Active/symptoms of central nervous system (CNS) disease
* Pregnancy or lactation

Primary outcomes:
measure: Acute Toxicity Associated With the Infusion of NiCord
timeFrame: 180 days post-transplant
measure: Proportion of Patients With Neutrophil Engraftment
timeFrame: 42 days
Secondary outcomes:
measure: Proportion of Patients Who Developed Acute GvHD Grade II-IV and III-IV
timeFrame: 180 days
measure: Non-relapse Mortality
timeFrame: 100 days
Other outcomes:
Locations:
city: Maywood
country: United States
facility: Loyola University, Cardinal Bernardin Cancer Center
state: Illinois
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Gamida Cell ltd
name: David Snyder, PhD
role: STUDY_DIRECTOR
affiliation: Duke University
name: Joanne Kurtzberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Mitchell Horwitz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Loyola University
name: Patrick Stiff, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Horwitz ME, Chao NJ, Rizzieri DA, Long GD, Sullivan KM, Gasparetto C, Chute JP, Morris A, McDonald C, Waters-Pick B, Stiff P, Wease S, Peled A, Snyder D, Cohen EG, Shoham H, Landau E, Friend E, Peleg I, Aschengrau D, Yackoubov D, Kurtzberg J, Peled T. Umbilical cord blood expansion with nicotinamide provides long-term multilineage engraftment. J Clin Invest. 2014 Jul;124(7):3121-8. doi: 10.1172/JCI74556. Epub 2014 Jun 9.
citation: Peled T, Shoham H, Aschengrau D, Yackoubov D, Frei G, Rosenheimer G N, Lerrer B, Cohen HY, Nagler A, Fibach E, Peled A. Nicotinamide, a SIRT1 inhibitor, inhibits differentiation and facilitates expansion of hematopoietic progenitor cells with enhanced bone marrow homing and engraftment. Exp Hematol. 2012 Apr;40(4):342-55.e1. doi: 10.1016/j.exphem.2011.12.005. Epub 2011 Dec 20.