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

Sponsor
Gamida Cell ltd (Industry)
Overall Status
Completed
CT.gov ID
NCT01221857
Collaborator
(none)
12
Enrollment
2
Locations
1
Arm
30
Duration (Months)
6
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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 Design

Study Type:
Interventional
Actual Enrollment :
12 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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 Start Date :
Nov 1, 2010
Actual Primary Completion Date :
Sep 1, 2012
Actual Study Completion Date :
May 1, 2013

Arms and Interventions

ArmIntervention/Treatment
Experimental: NiCord

Drug: NiCord®
NiCord® is a cell-based product composed of umbilical cord-derived ex vivo expanded stem and progenitor cells.

Outcome Measures

Primary Outcome Measures

  1. 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.

  2. 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

  1. 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.

  2. Non-relapse Mortality [100 days]

    Proportion of patients who had non-relapse mortality at 100 days.

Eligibility Criteria

Criteria

Ages Eligible for Study:
8 Years to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Loyola University, Cardinal Bernardin Cancer CenterMaywoodIllinoisUnited States60153
2Duke University Medical CenterDurhamNorth CarolinaUnited States27705

Sponsors and Collaborators

  • Gamida Cell ltd

Investigators

  • Study Director: David Snyder, PhD, Gamida Cell ltd
  • Principal Investigator: Joanne Kurtzberg, MD, Duke University
  • Principal Investigator: Mitchell Horwitz, MD, Duke University
  • Principal Investigator: Patrick Stiff, MD, Loyola University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Gamida Cell ltd
ClinicalTrials.gov Identifier:
NCT01221857
Other Study ID Numbers:
  • GC P#01.01.020
First Posted:
Oct 15, 2010
Last Update Posted:
Aug 3, 2021
Last Verified:
Aug 1, 2021

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail12 patients were enrolled/transplanted; efficacy results were summarized for 11 patients treated with NiCord. 1 patient was transplanted with unmanipulated cord only. Safety results were summarized for all patients.
Arm/Group TitleNiCord
Arm/Group DescriptionNiCord: NiCord is a cell-based product composed of umbilical cord-derived ex vivo expanded stem and progenitor cells.
Period Title: Overall Study
STARTED12
COMPLETED12
NOT COMPLETED0

Baseline Characteristics

Arm/Group TitleNiCord
Arm/Group DescriptionNiCord®: NiCord® is a cell-based product composed of umbilical cord-derived ex vivo expanded stem and progenitor cells.
Overall Participants12
Age (years) [Median (Full Range) ]
Median (Full Range) [years]
45
Age (Count of Participants)
<=18 years
0
0%
Between 18 and 65 years
12
100%
>=65 years
0
0%
Sex: Female, Male (Count of Participants)
Female
6
50%
Male
6
50%
Region of Enrollment (Count of Participants)
United States
12
100%

Outcome Measures

1. Primary Outcome
TitleAcute Toxicity Associated With the Infusion of NiCord
DescriptionAcute 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.
Time Frame180 days post-transplant

Outcome Measure Data

Analysis Population Description
Patients transplanted with NiCord
Arm/Group TitleNiCord
Arm/Group DescriptionAnalysis population is patients transplanted with NiCord plus unmanipulated cord blood unit.
Measure Participants11
Count of Participants [Participants]
0
0%
2. Primary Outcome
TitleProportion of Patients With Neutrophil Engraftment
DescriptionNeutrophil 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.
Time Frame42 days

Outcome Measure Data

Analysis Population Description
Patients transplanted with NiCord
Arm/Group TitleNeutrophil Engraftment
Arm/Group DescriptionPatients transplanted with NiCord plus unmanipulated cord blood unit.
Measure Participants11
Number [proportion of patients]
0.91
3. Secondary Outcome
TitleProportion of Patients Who Developed Acute GvHD Grade II-IV and III-IV
DescriptionAcute 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.
Time Frame180 days

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group TitleGrade II-IV GvHDGrade III-IV GvHD
Arm/Group DescriptionAll patients transplanted were assessed for acute GvHD grade II-IV.All patients transplanted were assessed for acute GvHD grade III-IV.
Measure Participants1111
Number [proportion of patients]
0.45
0
4. Secondary Outcome
TitleNon-relapse Mortality
DescriptionProportion of patients who had non-relapse mortality at 100 days.
Time Frame100 days

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group TitleNon-relapse Mortality
Arm/Group Descriptionproportion of patients with non-relapse mortality at 100 days
Measure Participants11
Number [proportion of patients]
0.09

Adverse Events

Time Frame
Adverse Event Reporting Description
Arm/Group TitleNiCord
Arm/Group DescriptionNiCord®: NiCord® is a cell-based product composed of umbilical cord-derived ex vivo expanded stem and progenitor cells.
All Cause Mortality
NiCord
Affected / at Risk (%)# Events
Total3/12 (25%)
Serious Adverse Events
NiCord
Affected / at Risk (%)# Events
Total8/12 (66.7%)
Blood and lymphatic system disorders
Graft rejection1/12 (8.3%) 1
Cardiac disorders
Hypertension2/12 (16.7%) 2
Supraventricular tachycardia1/12 (8.3%) 1
Gastrointestinal disorders
Gastrointestinal Disorder2/12 (16.7%) 2
Infections and infestations
Pneumonia1/12 (8.3%) 1
Investigations
Disease relapse1/12 (8.3%) 1
Psychiatric disorders
Depression1/12 (8.3%) 1
Altered mental status1/12 (8.3%) 1
Renal and urinary disorders
Hematuria1/12 (8.3%) 1
Acute renal failure1/12 (8.3%) 1
Respiratory, thoracic and mediastinal disorders
Hemoptysis1/12 (8.3%) 1
Other (Not Including Serious) Adverse Events
NiCord
Affected / at Risk (%)# Events
Total11/12 (91.7%)
Cardiac disorders
Hypertension6/12 (50%) 7
Hypotension1/12 (8.3%) 1
Tachycardia3/12 (25%) 3
Sinus bradycardia1/12 (8.3%) 1
Arrhythmia1/12 (8.3%) 1
Gastrointestinal disorders
Nausea4/12 (33.3%) 4
Elevated LFTs1/12 (8.3%) 1
CMV gastritis1/12 (8.3%) 1
Immune system disorders
aGvHD7/12 (58.3%) 10
Infections and infestations
CMV reactivation6/12 (50%) 6
HHV-6 Reactivation6/12 (50%) 6
Staph Coagulase Infection2/12 (16.7%) 3
BK virus infection2/12 (16.7%) 2
E coli infection1/12 (8.3%) 1
RSV infection1/12 (8.3%) 1
Pseudomonas infection1/12 (8.3%) 1
Enterococcus infection1/12 (8.3%) 1
Investigations
Hypomagnesemia4/12 (33.3%) 4
Hypocalcemia3/12 (25%) 3
Hypoalbuminemia1/12 (8.3%) 1
Renal and urinary disorders
Hematuria2/12 (16.7%) 2
Proteinuria3/12 (25%) 3
Cystitis1/12 (8.3%) 1
Respiratory, thoracic and mediastinal disorders
Hypoxia1/12 (8.3%) 1
Dyspnea1/12 (8.3%) 1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/TitleKelly Myers
OrganizationGamida Cell
Phone+972-2-659-5631
Emailclinicaltrials@gamida-cell.com
Responsible Party:
Gamida Cell ltd
ClinicalTrials.gov Identifier:
NCT01221857
Other Study ID Numbers:
  • GC P#01.01.020
First Posted:
Oct 15, 2010
Last Update Posted:
Aug 3, 2021
Last Verified:
Aug 1, 2021