UCBT: Safety and Tolerability of HSC835 in Patients With Hematological Malignancies Undergoing Single Umbilical Cord Blood Transplant

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01930162
• Collaborator: (none)
• Enrollment: 9
• Location: 1
• Arm: 1
• Actual Duration (Months): 22.7
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This study was designed to evaluate the safety and tolerability of HSC835 for clinical use as measured by the absence of graft failure at day 42 in excess of that currently observed with double umbilical cord blood (UCB) transplantation (DUCBT) with non-myeloablative (NMA) conditioning.

Condition or Disease	Intervention/Treatment	Phase
Single Umbilical Cord Blood Transplantation; Non-myeloablative Conditioning; Acute Lymphocytic Leukemia; Myelodysplastic Syndrome; Non-Hodgkin's Lymphoma; Multiple Myeloma; Chronic Lymphocytic Leukemia	Drug: HSC835	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: A Single-arm, Open-label Study to Evaluate the Safety and Tolerability of Infusing HSC835 in Patients With Hematological Malignancies Undergoing UCB Transplantation Using a Non-myeloablative Conditioning Regimen
• Actual Study Start Date: Oct 7, 2014
• Actual Primary Completion Date: Aug 29, 2016
• Actual Study Completion Date: Aug 29, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HSC835 Patients with hematologic malignancies requiring UCB transplant with a NMA conditioning regimen.	Drug: HSC835; HSC835 is a stem cell therapy product providing a source of Hematopoietic stem cell (HSC).

Outcome Measures

Primary Outcome Measures

1. Absence of Graft Failure at Day 42 [42 days]

   This endpoint was to study safety and tolerability of HSC835 as measured by the absence of graft failure at day 42 in excess of that currently observed with double umbilical cord blood (UCB) transplantation (DUCBT) with non-myeloablative (NMA) conditioning.

Secondary Outcome Measures

1. Incidence of Neutrophil Recovery Within 42 Days [42 days]

   Engraftment is defined as the first of three consecutive days with ANC > 0.5 x 109/L.

2. Incidence of Non-relapse Mortality (NRM) Within 100 Days and One Year [1 year]

   NRM includes all patients who died from any other cause except relapse of the underlying disease during the study duration.

3. Incidence of Overall Survival Within One Year [1 year]

   Overall survival is the proportion of patients who were alive at the end of the one year study period.

4. Incidence of Relapse-free Survival Within One Year [1 year]

   Patients are considered to have achieved relapse-free survival if they had not experienced either relapse or death (of any cause) at the end of the study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with a diagnosis that qualifies them for UCBT

• Adequate organ function

• Availability of eligible donor material

Exclusion Criteria:

• Pregnancy or breastfeeding women and women of child-bearing potential unless two acceptable forms of contraception are being used

• Human immunodeficiency virus (HIV) infection

• Active infection

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Minneapolis	Minnesota	United States	55455

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• A Plain Language Trial Summary is available on novartisclinicaltrials.com

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01930162
• Other Study ID Numbers: CHSC835X2202
• First Posted: Aug 28, 2013
• Last Update Posted: Jan 5, 2021
• Last Verified: Aug 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: HSC835; single umbilical cord blood transplantation; non-myeloablative conditioning regimen; Umbilical cord blood; UCB transplantation
• Additional relevant MeSH terms: Leukemia; Multiple Myeloma; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Hematologic Neoplasms; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes

Study Results

Participant Flow

Recruitment Details	Patients were enrolled into the study until approximately nine (9) patients were evaluable for safety as measured by the absence of infusional toxicity and sustained engraftment at Day 100.

Arm/Group Title	HSC835
Arm/Group Description	Patients with hematologic malignancies requiring UCB transplant with a NMA conditioning regimen.
Period Title: Overall Study
STARTED	9
COMPLETED	4
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	HSC835
Arm/Group Description	Patients with hematologic malignancies requiring UCB transplant with a NMA conditioning regimen.
Overall Participants	9
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.0 (13.16)
Sex: Female, Male (Count of Participants)
Female	3 33.3%
Male	6 66.7%

Outcome Measures

1. Primary Outcome

Title	Absence of Graft Failure at Day 42
Description	This endpoint was to study safety and tolerability of HSC835 as measured by the absence of graft failure at day 42 in excess of that currently observed with double umbilical cord blood (UCB) transplantation (DUCBT) with non-myeloablative (NMA) conditioning.
Time Frame	42 days

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: The Safety analysis included all enrolled patients who were transplanted with HSC835 (any patient with a date for HSC835 transplant).

Arm/Group Title	HSC835
Arm/Group Description	Patients with hematologic malignancies requiring UCB transplant with a NMA conditioning regimen.
Measure Participants	9
Number [Participants]	0 0%

2. Secondary Outcome

Title	Incidence of Neutrophil Recovery Within 42 Days
Description	Engraftment is defined as the first of three consecutive days with ANC > 0.5 x 109/L.
Time Frame	42 days

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: The Safety analysis included all enrolled patients who were transplanted with HSC835 (any patient with a date for HSC835 transplant).

Arm/Group Title	HSC835
Arm/Group Description	Patients with hematologic malignancies requiring UCB transplant with a NMA conditioning regimen.
Measure Participants	9
Number [Participants]	9 100%

3. Secondary Outcome

Title	Incidence of Non-relapse Mortality (NRM) Within 100 Days and One Year
Description	NRM includes all patients who died from any other cause except relapse of the underlying disease during the study duration.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: The Safety analysis included all enrolled patients who were transplanted with HSC835 (any patient with a date for HSC835 transplant).

Arm/Group Title	HSC835
Arm/Group Description	Patients with hematologic malignancies requiring UCB transplant with a NMA conditioning regimen.
Measure Participants	9
Number [Participants]	1 11.1%

4. Secondary Outcome

Title	Incidence of Overall Survival Within One Year
Description	Overall survival is the proportion of patients who were alive at the end of the one year study period.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: The Safety analysis included all enrolled patients who were transplanted with HSC835 (any patient with a date for HSC835 transplant).

Arm/Group Title	HSC835
Arm/Group Description	Patients with hematologic malignancies requiring UCB transplant with a NMA conditioning regimen.
Measure Participants	9
Number [Participants]	5 55.6%

5. Secondary Outcome

Title	Incidence of Relapse-free Survival Within One Year
Description	Patients are considered to have achieved relapse-free survival if they had not experienced either relapse or death (of any cause) at the end of the study.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: The Safety analysis included all enrolled patients who were transplanted with HSC835 (any patient with a date for HSC835 transplant).

Arm/Group Title	HSC835
Arm/Group Description	Patients with hematologic malignancies requiring UCB transplant with a NMA conditioning regimen.
Measure Participants	9
Number [Participants]	4 44.4%

Adverse Events

Time Frame	Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Arm/Group Title	Time Period From Transplant Until 48hrs After Transplant		Time Period From Day 3 up to End of Study
Arm/Group Description	Adverse events that occurred within the first 48 hours of transplant.		Adverse Events that occurred 48 hours post-transplant.
All Cause Mortality
	Time Period From Transplant Until 48hrs After Transplant		Time Period From Day 3 up to End of Study
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Time Period From Transplant Until 48hrs After Transplant		Time Period From Day 3 up to End of Study
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		9/9 (100%)
Gastrointestinal disorders
Oesophageal achalasia	0/9 (0%)		1/9 (11.1%)
Immune system disorders
Acute graft versus host disease	0/9 (0%)		6/9 (66.7%)
Infections and infestations
Cellulitis	0/9 (0%)		1/9 (11.1%)
Clostridium difficile infection	0/9 (0%)		2/9 (22.2%)
Cytomegalovirus viraemia	0/9 (0%)		1/9 (11.1%)
Human herpesvirus 6 infection	0/9 (0%)		1/9 (11.1%)
Pneumonia	0/9 (0%)		2/9 (22.2%)
Sepsis	0/9 (0%)		1/9 (11.1%)
Staphylococcal bacteraemia	0/9 (0%)		1/9 (11.1%)
Staphylococcal sepsis	0/9 (0%)		1/9 (11.1%)
Injury, poisoning and procedural complications
Transplant failure	0/9 (0%)		1/9 (11.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Chronic lymphocytic leukaemia recurrent	0/9 (0%)		1/9 (11.1%)
Malignant neoplasm progression	0/9 (0%)		1/9 (11.1%)
Myelodysplastic syndrome	0/9 (0%)		1/9 (11.1%)
Plasma cell myeloma recurrent	0/9 (0%)		1/9 (11.1%)
Nervous system disorders
Cognitive disorder	0/9 (0%)		1/9 (11.1%)
Encephalopathy	0/9 (0%)		1/9 (11.1%)
Psychiatric disorders
Mental status changes	0/9 (0%)		1/9 (11.1%)
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration	0/9 (0%)		2/9 (22.2%)
Vascular disorders
Deep vein thrombosis	0/9 (0%)		1/9 (11.1%)
Embolism	0/9 (0%)		1/9 (11.1%)
Hypotension	0/9 (0%)		1/9 (11.1%)
Other (Not Including Serious) Adverse Events
	Time Period From Transplant Until 48hrs After Transplant		Time Period From Day 3 up to End of Study
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/9 (88.9%)		6/9 (66.7%)
Blood and lymphatic system disorders
Febrile neutropenia	0/9 (0%)		2/9 (22.2%)
Cardiac disorders
Sinus bradycardia	1/9 (11.1%)		0/9 (0%)
Sinus tachycardia	1/9 (11.1%)		0/9 (0%)
Gastrointestinal disorders
Constipation	1/9 (11.1%)		0/9 (0%)
Diarrhoea	1/9 (11.1%)		0/9 (0%)
Dyspepsia	1/9 (11.1%)		0/9 (0%)
Nausea	1/9 (11.1%)		0/9 (0%)
Stomatitis	0/9 (0%)		1/9 (11.1%)
Vomiting	1/9 (11.1%)		0/9 (0%)
General disorders
Fatigue	1/9 (11.1%)		0/9 (0%)
Infections and infestations
Cellulitis	0/9 (0%)		1/9 (11.1%)
Cytomegalovirus viraemia	0/9 (0%)		3/9 (33.3%)
Enterococcal bacteraemia	0/9 (0%)		3/9 (33.3%)
Epstein-Barr viraemia	0/9 (0%)		1/9 (11.1%)
Human herpesvirus 6 infection	0/9 (0%)		1/9 (11.1%)
Methylobacterium infection	0/9 (0%)		1/9 (11.1%)
Pneumonia	0/9 (0%)		2/9 (22.2%)
Sinusitis	0/9 (0%)		1/9 (11.1%)
Metabolism and nutrition disorders
Decreased appetite	1/9 (11.1%)		0/9 (0%)
Fluid overload	3/9 (33.3%)		1/9 (11.1%)
Nervous system disorders
Headache	3/9 (33.3%)		0/9 (0%)
Renal and urinary disorders
Urinary hesitation	0/9 (0%)		1/9 (11.1%)
Vascular disorders
Deep vein thrombosis	0/9 (0%)		2/9 (22.2%)
Hypertension	4/9 (44.4%)		0/9 (0%)
Hypotension	1/9 (11.1%)		0/9 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.