Pilot Study Evaluating Safety & Efficacy of DCBT: NiCord® & UNM CBU to Patients With Hematological Malignancies

Phase 1

Completed

• Conditions: Acute Myelogenous Leukemia (AML); Non-Hodgkin's Lymphoma; Hodgkin's Disease; Acute Lymphoblastic Leukemia (ALL); Myelodysplastic Syndrome (MDS)
• Interventions: Drug: NiCord®

• Registration Number: NCT01221857
• Lead Sponsor: Gamida Cell ltd

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.

Study Timeline

• Study First Submitted: 2010-10-14
• Study First Submitted QC: 2010-10-14
• Study First Posted: 2010-10-15
• Study Start: 2010-11
• Primary Completion: 2012-09
• Study Completion: 2013-05
• Results First Submitted: 2017-05-24
• Results First Submitted QC: 2019-02-03
• Results First Posted: 2019-02-26
• Status Verified: 2021-08
• Last Update Submitted: 2021-08-01
• Last Update Posted: 2021-08-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
NiCord	NiCord®	-

Primary Outcome Measures

Name	Time	Method
Acute Toxicity Associated With the Infusion of NiCord	180 days post-transplant	Acute toxicity associated with the infusion of NiCord will be measured by adverse events within 24 hours post-infusion, defined as the acute toxicity period. Known adverse events associated with myeloablation and cord blood transplant were specifically monitored including fever, chills, allergic reaction/hypersensitivity, anaphylaxis, sinus bradycardia, sinus tachycardia, hypertension, hypotension, nausea, vomiting, diarrhea, dyspnea, hypoxia, hemoglobinuria, infection, flank pain and any other skin, CNS, cardiac, pulmonary or other toxicity manifestations.
Proportion of Patients With Neutrophil Engraftment	42 days	Neutrophil engraftment was defined as achieving an Absolute Neutrophil Count (ANC) of ≥500 mm3 for 3 consecutive measurements on different days by day 42 inclusive (the day of engraftment was defined as the first of these 3 days). The ANC recovery must be of donor origin documented by peripheral blood chimerism assays indicating less than or equal to 10% host cells in peripheral blood.

Secondary Outcome Measures

Name	Time	Method
Proportion of Patients Who Developed Acute GvHD Grade II-IV and III-IV	180 days	Acute GvHD was assessed from transplantation (day 0) until day 99 post-transplant or more frequently as clinically indicated. GvHD was classified according to the Glucksberg Classification (Glucksberg, Storb et al. 1974).; The overall grade of GvHD, however, was determined by an assessment of skin disease, liver disease and gastrointestinal manifestations.
Non-relapse Mortality	100 days	Proportion of patients who had non-relapse mortality at 100 days.

Trial Locations

Locations (2)

Loyola University, Cardinal Bernardin Cancer Center; 🇺🇸 Maywood, Illinois, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States