Reduced Intensity Conditioning for Umbilical Cord Blood Transplant in Pediatric Patients With Non-Malignant Disorders

• ClinicalTrials.gov Identifier: NCT00744692
• Recruitment Status: Completed
• First Posted: September 1, 2008
• Results First Posted: August 13, 2014
• Last Update Posted: August 13, 2014
• Sponsor: Duke University
• Information provided by (Responsible Party): Duke University

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Non Malignant Disorders; Immunodeficiencies; Congenital Marrow Failures; Hemoglobinopathies; Inborn Errors of Metabolism; Sickle Cell; Thalassemia; Lysosomal Storage Disease
• Interventions: Biological: Unrelated Umbilical Cord Blood Transplant; Drug: Reduced Intensity Conditioning
• Enrollment: 22

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	RIC Cord Blood Transplant
Arm/Group Description	Reduced Intensity Conditioning for Umbilical Cord Blood Transplant Unrelated Umbilical Cord Blood Transplant: Reduced Intensity Conditioning for unrelated umbilical cord blood transplant Reduced Intensity Conditioning
Period Title: Overall Study
Started	22
Completed	22
Not Completed	0

Baseline Characteristics

Arm/Group Title		RIC Cord Blood Transplant
Arm/Group Description		Reduced Intensity Conditioning for Umbilical Cord Blood Transplant Unrelated Umbilical Cord Blood Transplant: Reduced Intensity Conditioning for unrelated umbilical cord blood transplant Reduced Intensity Conditioning
Overall Number of Baseline Participants		22
Baseline Analysis Population Description		22 subjects undergoing umbilical cord blood transplant
Age, Continuous [1]; Median (Full Range); Unit of measure: Years
	Number Analyzed	22 participants
		2.83; (0.3 to 8)
		[1] Measure Description: Age (in years) on the day of transplant
Age, Categorical [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	22 participants
	<=18 years	22 100.0%
	Between 18 and 65 years	0 0.0%
	>=65 years	0 0.0%
		[1] Measure Description: Age (years) on the day of transplant
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	22 participants
	Female	9 40.9%
	Male	13 59.1%

Outcome Measures

1. Primary Outcome

Title	Determine the Feasibility of Attaining Acceptable Rates of Donor Cell Engraftment (>25% Donor Cells at 180 Days) Following RIC Regimens in Children < 21 Years Receiving UCBT for Non-malignant Disorders.
Description	Determine the feasibility of attaining acceptable rates of donor cell engraftment (>25% donor cells at 180 days) following reduced intensity conditioning regimens in children < 21 years receiving cord blood transplant for non-malignant disorders.
Time Frame	180 days post transplant

Outcome Measure Data

Analysis Population Description

Of the 22 patients enrolled, 18 patients were alive at 180 days, the time-point for primary end point

Arm/Group Title	RIC Cord Blood Transplant
Arm/Group Description:	Reduced Intensity Conditioning for Umbilical Cord Blood Transplant Unrelated Umbilical Cord Blood Transplant: Reduced Intensity Conditioning for unrelated umbilical cord blood transplant Reduced Intensity Conditioning
Overall Number of Participants Analyzed	18
Measure Type: Number; Unit of Measure: % of participants
	88

2. Secondary Outcome

Title	To Describe the Pace of Neutrophil Recovery
Description	Neutrophil recovery was defined as the first day of an absolute neutrophil count (ANC) more than 500/uL for 3 consecutive days not secondary to granulocyte infusions
Time Frame	42 days post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RIC Cord Blood Transplant
Arm/Group Description:	Reduced Intensity Conditioning for Umbilical Cord Blood Transplant Unrelated Umbilical Cord Blood Transplant: Reduced Intensity Conditioning for unrelated umbilical cord blood transplant Reduced Intensity Conditioning
Overall Number of Participants Analyzed	22
Median (Full Range); Unit of Measure: days
	20; (12 to 28)

3. Secondary Outcome

Title	To Evaluate the Pace of Immune Reconstitution.
Description	Immune reconstitution after RIC in UCBT was described. CD4 count is a standard measure of immune reconstitution and is described here. Additional data is available upon request.
Time Frame	1 year post transplant

Outcome Measure Data

Analysis Population Description

Of the 22 patients at baseline, 5 patients died early before a year; and 2 additional patients had early graft failure. Thus 7 patients were not available for analysis of Immune reconstitution endpoint. CD4 count is reported here.

Arm/Group Title	RIC Cord Blood Transplant
Arm/Group Description:	Reduced Intensity Conditioning for Umbilical Cord Blood Transplant Unrelated Umbilical Cord Blood Transplant: Reduced Intensity Conditioning for unrelated umbilical cord blood transplant Reduced Intensity Conditioning
Overall Number of Participants Analyzed	15
Median (Full Range); Unit of Measure: cells/uL
	805; (6 to 2013)

4. Secondary Outcome

Title	To Determine the Overall Survival at day180 Post-transplant
Description	To determine the overall survival at day180 post-transplant: determined by Kaplan Meier survival analysis
Time Frame	180 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RIC Cord Blood Transplant
Arm/Group Description:	Reduced Intensity Conditioning for Umbilical Cord Blood Transplant Unrelated Umbilical Cord Blood Transplant: Reduced Intensity Conditioning for unrelated umbilical cord blood transplant Reduced Intensity Conditioning
Overall Number of Participants Analyzed	22
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	81.8; (58.5 to 92.8)

5. Secondary Outcome

Title	To Describe Incidence of Acute Graft Versus Host Disease (GVHD) (II - IV)
Description	To describe incidence of acute Graft Versus Host Disease (GVHD) (II - IV) : measured by cumulative incidence analysis
Time Frame	100 days post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RIC Cord Blood Transplant
Arm/Group Description:	Reduced Intensity Conditioning for Umbilical Cord Blood Transplant Unrelated Umbilical Cord Blood Transplant: Reduced Intensity Conditioning for unrelated umbilical cord blood transplant Reduced Intensity Conditioning
Overall Number of Participants Analyzed	22
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	22.7; (5.3 to 40.1)

6. Secondary Outcome

Title	To Describe the Incidence of Grade 3-4 Organ Toxicity
Description	[Not Specified]
Time Frame	2 years post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RIC Cord Blood Transplant
Arm/Group Description:	Reduced Intensity Conditioning for Umbilical Cord Blood Transplant Unrelated Umbilical Cord Blood Transplant: Reduced Intensity Conditioning for unrelated umbilical cord blood transplant Reduced Intensity Conditioning
Overall Number of Participants Analyzed	22
Measure Type: Number; Unit of Measure: participants
	0

7. Secondary Outcome

Title	To Evaluate Long-term Complications, Such as Sterility, Endocrinopathy, and Growth Failure
Description	[Not Specified]
Time Frame	at least 2 years post transplant

Outcome Measure Data

Analysis Population Description

Of the 22 patients at baseline, 5 patients died early before a year; and 2 additional patients had early graft failure. Thus 7 patients were not available for analysis of this 2 year late effects endpoint.

Arm/Group Title	RIC Cord Blood Transplant
Arm/Group Description:	Reduced Intensity Conditioning for Umbilical Cord Blood Transplant Unrelated Umbilical Cord Blood Transplant: Reduced Intensity Conditioning for unrelated umbilical cord blood transplant Reduced Intensity Conditioning
Overall Number of Participants Analyzed	15
Measure Type: Number; Unit of Measure: percentage of patients
	0

8. Secondary Outcome

Title	To Evaluate the Incidence of Late Graft Failures at 2 Years Post-transplant
Description	[Not Specified]
Time Frame	2 years post transplant

Outcome Measure Data

Analysis Population Description

Of the 22 patients at baseline, 5 patients died early before a year; and 2 additional patients had early graft failure. Thus 7 patients were not available for analysis of this 2 year late graft failure endpoint.

Arm/Group Title	RIC Cord Blood Transplant
Arm/Group Description:	Reduced Intensity Conditioning for Umbilical Cord Blood Transplant Unrelated Umbilical Cord Blood Transplant: Reduced Intensity Conditioning for unrelated umbilical cord blood transplant Reduced Intensity Conditioning
Overall Number of Participants Analyzed	15
Measure Type: Number; Unit of Measure: participants
	0

9. Secondary Outcome

Title	To Describe the Pace of Platelet Recovery
Description	Platelet engraftment was defined as the first day of platelet counts more than 50,000/uL for 7 consecutive days without transfusions
Time Frame	180 days post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RIC Cord Blood Transplant
Arm/Group Description:	Reduced Intensity Conditioning for Umbilical Cord Blood Transplant Unrelated Umbilical Cord Blood Transplant: Reduced Intensity Conditioning for unrelated umbilical cord blood transplant Reduced Intensity Conditioning
Overall Number of Participants Analyzed	22
Median (Full Range); Unit of Measure: days
	48; (33 to 144)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	Adverse events that were expected and non-serious were not collected in this study.
Arm/Group Title	RIC Cord Blood Transplant
Arm/Group Description	Reduced Intensity Conditioning for Umbilical Cord Blood Transplant Unrelated Umbilical Cord Blood Transplant: Reduced Intensity Conditioning for unrelated umbilical cord blood transplant Reduced Intensity Conditioning
All-Cause Mortality
	RIC Cord Blood Transplant
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	RIC Cord Blood Transplant
	Affected / at Risk (%)
Total	18/22 (81.82%)
Blood and lymphatic system disorders
Auto Immune Hemolytic Anemia	2/22 (9.09%)
Hemolytic Transfusion Reaction	1/22 (4.55%)
Graft Failure Post Transplant	2/22 (9.09%)
Deep Vein Thrombosis	1/22 (4.55%)
Endocrine disorders
Hyperglycemia	1/22 (4.55%)
Gastrointestinal disorders
Abdominal Pain	1/22 (4.55%)
GI Distress	3/22 (13.64%)
Pnematosis	1/22 (4.55%)
General disorders
Multi System Organ Failure	2/22 (9.09%)
Graft Versus Host Disease	4/22 (18.18%)
Infections and infestations
Infection	12/22 (54.55%)
Sepsis	3/22 (13.64%)
Investigations
Fever	5/22 (22.73%)
Metabolism and nutrition disorders
Dehydration	2/22 (9.09%)
Nervous system disorders
VP Shunt Malfunction	1/22 (4.55%)
Seizure	1/22 (4.55%)
Posterior Reversible Encephalopathy Syndrome	1/22 (4.55%)
Renal and urinary disorders
Nephrotic Syndrome	1/22 (4.55%)
Respiratory, thoracic and mediastinal disorders
Respiratory Distress	2/22 (9.09%)
Respiratory Failure	1/22 (4.55%)
Skin and subcutaneous tissue disorders
Necrotic Ulcer (skin)	1/22 (4.55%)
Surgical and medical procedures
Central Line Removal	1/22 (4.55%)
Dental Rehabilitation	1/22 (4.55%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	RIC Cord Blood Transplant
	Affected / at Risk (%)
Total	0/22 (0.00%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Dr. Suhag Parikh
• Organization: Duke University Medical Center
• Phone: 919-668-1100
• EMail: suhag.parikh@dm.duke.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Parikh SH, Mendizabal A, Benjamin CL, Komanduri KV, Antony J, Petrovic A, Hale G, Driscoll TA, Martin PL, Page KM, Flickinger K, Moffet J, Niedzwiecki D, Kurtzberg J, Szabolcs P. A novel reduced-intensity conditioning regimen for unrelated umbilical cord blood transplantation in children with nonmalignant diseases. Biol Blood Marrow Transplant. 2014 Mar;20(3):326-36. doi: 10.1016/j.bbmt.2013.11.021. Epub 2013 Dec 1.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT00744692
• Other Study ID Numbers: Pro00008753
• First Submitted: August 28, 2008
• First Posted: September 1, 2008
• Results First Submitted: July 23, 2014
• Results First Posted: August 13, 2014
• Last Update Posted: August 13, 2014