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)
• Enrollment: 12
• Locations: 2
• Arm: 1
• Duration (Months): 30
• Patients Per Site: 6
• Patients Per Site Per Month: 0.2

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

Condition or Disease	Intervention/Treatment	Phase
Acute Lymphoblastic Leukemia (ALL); Acute Myelogenous Leukemia (AML); Myelodysplastic Syndrome (MDS); Non-Hodgkin's Lymphoma; Hodgkin's Disease	Drug: NiCord®	Phase 1/Phase 2

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

Arm	Intervention/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

	Site	City	State	Country	Postal Code
1	Loyola University, Cardinal Bernardin Cancer Center	Maywood	Illinois	United States	60153
2	Duke University Medical Center	Durham	North Carolina	United States	27705

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:

• Gamida Cell Ltd.
• Duke University Medical Center
• Loyola University

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

• Keywords provided by Gamida Cell ltd: Double Umbilical Cord Blood Stem Cell Transplantation; Hematological Malignancies; HLA Mismatched Donors; Cord Blood Transplantation
• Additional relevant MeSH terms: Leukemia; Neoplasms; Preleukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Hematologic Neoplasms; Hodgkin Disease; Myelodysplastic Syndromes

Study Results

Participant Flow

Pre-assignment Detail	12 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 Title	NiCord
Arm/Group Description	NiCord: NiCord is a cell-based product composed of umbilical cord-derived ex vivo expanded stem and progenitor cells.
Period Title: Overall Study
STARTED	12
COMPLETED	12
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	NiCord
Arm/Group Description	NiCord®: NiCord® is a cell-based product composed of umbilical cord-derived ex vivo expanded stem and progenitor cells.
Overall Participants	12
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

Title	Acute Toxicity Associated With the Infusion of NiCord
Description	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.
Time Frame	180 days post-transplant

Outcome Measure Data

Analysis Population Description

Patients transplanted with NiCord

Arm/Group Title	NiCord
Arm/Group Description	Analysis population is patients transplanted with NiCord plus unmanipulated cord blood unit.
Measure Participants	11
Count of Participants [Participants]	0 0%

2. Primary Outcome

Title	Proportion of Patients With Neutrophil Engraftment
Description	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.
Time Frame	42 days

Outcome Measure Data

Analysis Population Description

Patients transplanted with NiCord

Arm/Group Title	Neutrophil Engraftment
Arm/Group Description	Patients transplanted with NiCord plus unmanipulated cord blood unit.
Measure Participants	11
Number [proportion of patients]	0.91

3. Secondary Outcome

Title	Proportion of Patients Who Developed Acute GvHD Grade II-IV and III-IV
Description	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.
Time Frame	180 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Grade II-IV GvHD	Grade III-IV GvHD
Arm/Group Description	All patients transplanted were assessed for acute GvHD grade II-IV.	All patients transplanted were assessed for acute GvHD grade III-IV.
Measure Participants	11	11
Number [proportion of patients]	0.45	0

4. Secondary Outcome

Title	Non-relapse Mortality
Description	Proportion of patients who had non-relapse mortality at 100 days.
Time Frame	100 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Non-relapse Mortality
Arm/Group Description	proportion of patients with non-relapse mortality at 100 days
Measure Participants	11
Number [proportion of patients]	0.09

Adverse Events

Arm/Group Title	NiCord
Arm/Group Description	NiCord®: 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
Total	3/12 (25%)
Serious Adverse Events
	NiCord
	Affected / at Risk (%)	# Events
Total	8/12 (66.7%)
Blood and lymphatic system disorders
Graft rejection	1/12 (8.3%)	1
Cardiac disorders
Hypertension	2/12 (16.7%)	2
Supraventricular tachycardia	1/12 (8.3%)	1
Gastrointestinal disorders
Gastrointestinal Disorder	2/12 (16.7%)	2
Infections and infestations
Pneumonia	1/12 (8.3%)	1
Investigations
Disease relapse	1/12 (8.3%)	1
Psychiatric disorders
Depression	1/12 (8.3%)	1
Altered mental status	1/12 (8.3%)	1
Renal and urinary disorders
Hematuria	1/12 (8.3%)	1
Acute renal failure	1/12 (8.3%)	1
Respiratory, thoracic and mediastinal disorders
Hemoptysis	1/12 (8.3%)	1
Other (Not Including Serious) Adverse Events
	NiCord
	Affected / at Risk (%)	# Events
Total	11/12 (91.7%)
Cardiac disorders
Hypertension	6/12 (50%)	7
Hypotension	1/12 (8.3%)	1
Tachycardia	3/12 (25%)	3
Sinus bradycardia	1/12 (8.3%)	1
Arrhythmia	1/12 (8.3%)	1
Gastrointestinal disorders
Nausea	4/12 (33.3%)	4
Elevated LFTs	1/12 (8.3%)	1
CMV gastritis	1/12 (8.3%)	1
Immune system disorders
aGvHD	7/12 (58.3%)	10
Infections and infestations
CMV reactivation	6/12 (50%)	6
HHV-6 Reactivation	6/12 (50%)	6
Staph Coagulase Infection	2/12 (16.7%)	3
BK virus infection	2/12 (16.7%)	2
E coli infection	1/12 (8.3%)	1
RSV infection	1/12 (8.3%)	1
Pseudomonas infection	1/12 (8.3%)	1
Enterococcus infection	1/12 (8.3%)	1
Investigations
Hypomagnesemia	4/12 (33.3%)	4
Hypocalcemia	3/12 (25%)	3
Hypoalbuminemia	1/12 (8.3%)	1
Renal and urinary disorders
Hematuria	2/12 (16.7%)	2
Proteinuria	3/12 (25%)	3
Cystitis	1/12 (8.3%)	1
Respiratory, thoracic and mediastinal disorders
Hypoxia	1/12 (8.3%)	1
Dyspnea	1/12 (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.