Allogeneic Hematopoietic Stem Cell Transplant For Epidermolysis Bullosa

• ClinicalTrials.gov Identifier: NCT00478244
• Recruitment Status: Terminated
• First Posted: May 24, 2007
• Results First Posted: February 11, 2013
• Last Update Posted: December 28, 2017
• Sponsor: Masonic Cancer Center, University of Minnesota
• Information provided by (Responsible Party): Masonic Cancer Center, University of Minnesota

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Epidermolysis Bullosa
• Interventions: Drug: busulfan; Drug: cyclophosphamide; Drug: fludarabine phosphate; Procedure: hematopoietic bone marrow transplantation
• Enrollment: 7

Participant Flow

Recruitment Details
Pre-assignment Details	All subjects were registered with the BMT Biostatistical Support Group at the University of Minnesota.

Arm/Group Title	Epidermolysis Bullosa (EB) Patients
Arm/Group Description	Epidermolysis bullosa patients enrolled for treatment with chemotherapy (Busulfan 0.8 or 1.1 mg/kg Days 6-9 before transplant; Fludarabine 25 mg/m^2 Days 3-5 before transplant; Cyclophosphamide 50 mg/kg Days 2-5 before transplant) and stem cell infusion (Day 0) followed by donor epidermal transplant .
Period Title: Overall Study
Started	7
Completed	6
Not Completed	1
Reason Not Completed
Did not receive transplant	1

Baseline Characteristics

Arm/Group Title		Epidermolysis Bullosa (EB) Patients
Arm/Group Description		Epidermolysis bullosa patients enrolled for treatment with chemotherapy (Busulfan 0.8 or 1.1 mg/kg Days 6-9 before transplant; Fludarabine 25 mg/m^2 Days 3-5 before transplant; Cyclophosphamide 50 mg/kg Days 2-5 before transplant) and stem cell infusion (Day 0) followed by donor epidermal transplant .
Overall Number of Baseline Participants		7
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	7 participants
	<=18 years	7 100.0%
	Between 18 and 65 years	0 0.0%
	>=65 years	0 0.0%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	7 participants
		6.0 (4.5)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	7 participants
	Female	4 57.1%
	Male	3 42.9%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	7 participants
		7

Outcome Measures

1. Primary Outcome

Title	Number of Patients With Detectable Collagen Type VII
Description	Number of patients with epidermolysis bullosa who had collagen type VII. Type VII collagen defects cause recessive dystrophic epidermolysis bullosa (RDEB), a blistering skin disorder often accompanied by epidermal cancers.
Time Frame	Day 100 Post Transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Evaluable Patients
Arm/Group Description:	Includes only patients that received transplant (one patient died prior to transplant).
Overall Number of Participants Analyzed	6
Measure Type: Number; Unit of Measure: participants
	5

2. Secondary Outcome

Title	Number of Patients With >70% Donor Chimerism
Description	Number of patients with donor chimerism - percentage of donor cells in the patient via the peripheral blood or bone marrow.
Time Frame	Days 21, 100, 180, 365 and 730 Post Transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Evaluable Patients
Arm/Group Description:	Includes only patients that received transplant (one patient died prior to transplant).
Overall Number of Participants Analyzed	6
Measure Type: Number; Unit of Measure: participants
Day 21	6
Day 100	5
Day 180	5
Day 365	5
Day 730	5

3. Secondary Outcome

Title	Number of Patients With Transplant-Related Mortality
Description	Number of patients who died due to complications of the transplant (includes all deaths without previous relapse or progression).
Time Frame	Day 180 Post Transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Evaluable Patients
Arm/Group Description:	Includes only patients that received transplant (one patient died prior to transplant).
Overall Number of Participants Analyzed	6
Measure Type: Number; Unit of Measure: participants
	0

4. Secondary Outcome

Title	Number of Patients With Platelet Engraftment
Description	Number of patients with a platelet count >5 x 10^10 cells/liter for 3 consecutive measurements.
Time Frame	Day 180 Post Transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Evaluable Patients
Arm/Group Description:	Includes only patients that received transplant (one patient died prior to transplant).
Overall Number of Participants Analyzed	6
Measure Type: Number; Unit of Measure: participants
	5

5. Secondary Outcome

Title	Number of Patients With Acute Graft-Versus-Host Disease (GVHD)
Description	Number of patients with GVHD. Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.
Time Frame	Day 100 Post Transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Evaluable Patients
Arm/Group Description:	Includes only patients that received transplant (one patient died prior to transplant).
Overall Number of Participants Analyzed	6
Measure Type: Number; Unit of Measure: participants
	1

6. Secondary Outcome

Title	Number of Patients With Chronic Graft-Versus-Host Disease (cGVHD)
Description	Number of patients with cGVHD; a severe long-term complication created by infusion of donor cells into a foreign host.
Time Frame	Day 365 Post Transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Evaluable Patients
Arm/Group Description:	Includes only patients that received transplant (one patient died prior to transplant).
Overall Number of Participants Analyzed	6
Measure Type: Number; Unit of Measure: participants
	0

7. Secondary Outcome

Title	Overall Survival
Description	Survival is defined as the number of patients that were alive post transplant.
Time Frame	1 year and 2 years Post Transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Evaluable Patients
Arm/Group Description:	Includes only patients that received transplant (one patient died prior to transplant).
Overall Number of Participants Analyzed	6
Measure Type: Number; Unit of Measure: participants
1 Year Post Transplant	5
2 Years Post Transplant	5

8. Secondary Outcome

Title	Number of Patients With Donor Derived Cells in Skin
Description	Number of patients who had donor skin chimerism - donor cells in the patient's epidermis (a state in bone marrow transplantation in which bone marrow and host cells exist compatibly without signs of graft-versus-host rejection disease).
Time Frame	Day 90 Post Transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Evaluable Patients
Arm/Group Description:	Includes only patients that received transplant (one patient died prior to transplant).
Overall Number of Participants Analyzed	6
Measure Type: Number; Unit of Measure: participants
	6

9. Secondary Outcome

Title	Number of Patients With Resistance to Blister Formation
Description	Resistance to Blister Formation demonstrated by response to negative pressure.
Time Frame	Month 1 through Month 24 Inclusive

Outcome Measure Data

Analysis Population Description

Added blister formation testing later in study; only 2 patients had pre-transplant test.

Arm/Group Title	Evaluable Patients
Arm/Group Description:	Includes only patients that received transplant (one patient died prior to transplant).
Overall Number of Participants Analyzed	2
Measure Type: Number; Unit of Measure: participants
	2

10. Secondary Outcome

Title	Number of Patients With Neutrophil Engraftment
Description	Number of patients with an absolute neutrophil count >5 x 10^8 cells/liter for 3 consecutive days.
Time Frame	Day 42 Post Transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Evaluable Patients
Arm/Group Description:	Includes only patients that received transplant (one patient died prior to transplant).
Overall Number of Participants Analyzed	6
Measure Type: Number; Unit of Measure: participants
	6

Adverse Events

Time Frame	All subjects were monitored continuously and only serious unexpected and selected serious adverse experiences were collected during the first 100 days after cell infusion.
Adverse Event Reporting Description	Serious adverse events include: marrow engraftment failure, severe acute graft-versus-host (GVHD) (Grades III and IV), and death. Death was collected on 6 of 7 patients enrolled.
Arm/Group Title	Epidermolysis Bullosa (EB) Patients
Arm/Group Description	Epidermolysis bullosa patients enrolled for treatment with chemotherapy (Busulfan 0.8 or 1.1 mg/kg Days 6-9 before transplant; Fludarabine 25 mg/m^2 Days 3-5 before transplant; Cyclophosphamide 50 mg/kg Days 2-5 before transplant) and stem cell infusion (Day 0) followed by donor epidermal transplant .
All-Cause Mortality
	Epidermolysis Bullosa (EB) Patients
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Epidermolysis Bullosa (EB) Patients
	Affected / at Risk (%)	# Events
Total	6/7 (85.71%)
Blood and lymphatic system disorders
Graft failure † 1	1/7 (14.29%)	1
General disorders
Death † 1	1/7 (14.29%)	1
Infections and infestations
Bacterial infection † 1	6/7 (85.71%)	6
Fungal infection † 1 [1]	2/7 (28.57%)	2
Viral infection † 1	1/7 (14.29%)	4
Metabolism and nutrition disorders
Hyperbilirubinemia † 1	4/7 (57.14%)	4
Renal and urinary disorders
Hemorrhagic cystitis † 1	1/7 (14.29%)	1
Renal insufficiency † 1	2/7 (28.57%)	2
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome † 1	1/7 (14.29%)	1
Skin and subcutaneous tissue disorders
Grade IV skin toxicity † 1	1/7 (14.29%)	1
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, CTCAE (4.0); [1] Candida sepsis
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Epidermolysis Bullosa (EB) Patients
	Affected / at Risk (%)	# Events
Total	0/7 (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: John E. Wagner, M.D.
• Organization: Masonic Cancer Center, University of Minnesota
• Phone: 612-626-2961
• EMail: wagne002@umn.edu

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

Wagner JE, Ishida-Yamamoto A, McGrath JA, Hordinsky M, Keene DR, Woodley DT, Chen M, Riddle MJ, Osborn MJ, Lund T, Dolan M, Blazar BR, Tolar J. Bone marrow transplantation for recessive dystrophic epidermolysis bullosa. N Engl J Med. 2010 Aug 12;363(7):629-39. doi: 10.1056/NEJMoa0910501. Erratum in: N Engl J Med. 2010 Sep 30;363(14):1383. Woodley, David T [added]; Chen, Mei [added].

• Responsible Party: Masonic Cancer Center, University of Minnesota
• ClinicalTrials.gov Identifier: NCT00478244
• Other Study ID Numbers: MT2006-15; CDR0000546620 ( Other Identifier: PDQ ); UMN-0702M01504 ( Other Identifier: IRB, University of Minnesota )
• First Submitted: May 23, 2007
• First Posted: May 24, 2007
• Results First Submitted: July 17, 2012
• Results First Posted: February 11, 2013
• Last Update Posted: December 28, 2017