A Pilot Study of HSCT for Patients With High-risk Hemoglobinopathy Using a Nonmyeloablative Preparative Regimen

• ClinicalTrials.gov Identifier: NCT00427661
• Recruitment Status: Completed
• First Posted: January 29, 2007
• Results First Posted: August 18, 2016
• Last Update Posted: August 18, 2016
• Sponsor: University of Pittsburgh
• Information provided by (Responsible Party): Lakshmanan Krishnamurti, University of Pittsburgh

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Sickle Cell Disease; Thalassemia; Hemoglobinopathies
• Intervention: Other: Busulfan; Fludarabine; cyclosporine A and MMF
• Enrollment: 8

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	AHSC in Severe SCD
Arm/Group Description	The patient population for this study included severe SCD patients, both pediatric and adult, who did not have end-organ failure, and met all of the eligibility criteria.
Period Title: Overall Study
Started	8
Completed	8
Not Completed	0

Baseline Characteristics

Arm/Group Title		AHSC in Severe SCD
Arm/Group Description		The patient population for this study included severe SCD patients, both pediatric and adult, who did not have end-organ failure, and met all of the eligibility criteria.
Overall Number of Baseline Participants		8
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	8 participants
	<=18 years	6 75.0%
	Between 18 and 65 years	2 25.0%
	>=65 years	0 0.0%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	8 participants
	Female	4 50.0%
	Male	4 50.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	8 participants
		8

Outcome Measures

1. Primary Outcome

Title	Development of GVHD Within 1 Year of BMT
Description	GVHD is assessed by physical exam, bloodwork and biopsy.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AHSC in Severe SCD
Arm/Group Description:	The patient population for this study included severe SCD patients, both pediatric and adult, who did not have end-organ failure, and met all of the eligibility criteria.
Overall Number of Participants Analyzed	7
Measure Type: Number; Unit of Measure: participants
	2

2. Primary Outcome

Title	Engraftment at 1 Year Post BMT.
Description	Measurement of total PBMC chimerism
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AHSC in Severe SCD
Arm/Group Description:	The patient population for this study included severe SCD patients, both pediatric and adult, who did not have end-organ failure, and met all of the eligibility criteria.
Overall Number of Participants Analyzed	7
Measure Type: Number; Unit of Measure: participants
	6

3. Secondary Outcome

Title	Incidence of Grade 2-4 Acute GVHD.
Description	[Not Specified]
Time Frame	100 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental
Arm/Group Description:	Busulfan, Fludarabine, Cyclosporine, MMF
Overall Number of Participants Analyzed	8
Measure Type: Number; Unit of Measure: participants with grade 2-4 AGVHD
	1

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	AHSC in Severe SCD
Arm/Group Description	The patient population for this study included severe SCD patients, both pediatric and adult, who did not have end-organ failure, and met all of the eligibility criteria.
All-Cause Mortality
	AHSC in Severe SCD
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	AHSC in Severe SCD
	Affected / at Risk (%)	# Events
Total	1/8 (12.50%)
Respiratory, thoracic and mediastinal disorders
Pulmonary Arterial Hypertension † [1]	1/8 (12.50%)
† Indicates events were collected by systematic assessment; [1] 21 year old female patient developed complications related to sickle cell disease associated progressive pulmonary arterial hypertension and died 10 months post BMT.
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	AHSC in Severe SCD
	Affected / at Risk (%)	# Events
Total	8/8 (100.00%)
Gastrointestinal disorders
Pancreatitis † [1]	1/8 (12.50%)	1
Poor oral intake † [2]	2/8 (25.00%)	2
Infections and infestations
Line related bacteremia † [3]	1/8 (12.50%)	1
Infection † [4]	1/8 (12.50%)	1
Line related bacteremia † [5]	1/8 (12.50%)	1
Nervous system disorders
Seizure † [6]	1/7 (14.29%)	1
Headache † [7]	1/8 (12.50%)	1
Renal and urinary disorders
Hemoglobinuria † [8]	1/8 (12.50%)	1
† Indicates events were collected by systematic assessment; [1] Mild pancreatitis Day +109 (Krishnamurti et al., 2008. Biol Blood Marrow Transplant 14:1270); [2] Required transient parenteral alimentation (Krishnamurti et al., 2008. Biol Blood Marrow Transplant 14:1270); [3] line related bacteremia with Rhizobium radiobactor d100 (Krishnamurti et al., 2008. Biol Blood Marrow Transplant 14:1270.; [4] Dermatomal herpes zoster Parainfluenza A infection (Krishnamurti et al., 2008. Biol Blood Marrow Transplant 14:1270); [5] Line related bacteremia d244 (Krishnamurti et al., 2008. Biol Blood Marrow Transplant 14:1270); [6] Seizure day+11 secondary to low level of phenytoin (Krishnamurti et al., 2008. Biol Blood Marrow Transplant 14:1270.); [7] headache day +1-+4, post transplant, requiring analgesics (Krishnamurti et al., 2008. Biol Blood Marrow Transplant 14:1270); [8] Hemoglobinuria immediately following stem cell transplant the resolved within 48 hours (Krishnamurti et al., 2008. Biol Blood Marrow Transplant 14:1270)

Limitations and 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/Title: Nancy Harter-Administrative Director of Research
• Organization: University of Pittsburgh-Department of Pediatrics
• Phone: 412-692-7487
• EMail: harterne@upmc.edu

• Responsible Party: Lakshmanan Krishnamurti, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT00427661
• Other Study ID Numbers: IRB #0504048
• First Submitted: January 18, 2007
• First Posted: January 29, 2007
• Results First Submitted: February 19, 2016
• Results First Posted: August 18, 2016
• Last Update Posted: August 18, 2016