Trial Outcomes & Findings for Allogeneic Hematopoietic Stem Cell Transplant For Epidermolysis Bullosa (NCT NCT00478244)

NCT ID: NCT00478244

Last Updated: 2017-12-28

Results Overview

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.

• Recruitment status: TERMINATED
• Study phase: NA
• Target enrollment: 7 participants
• Primary outcome timeframe: Day 100 Post Transplant
• Results posted on: 2017-12-28

Participant Flow

All subjects were registered with the BMT Biostatistical Support Group at the University of Minnesota.

Participant milestones

Measure	Epidermolysis Bullosa (EB) Patients 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 Study STARTED	7
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	Epidermolysis Bullosa (EB) Patients 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 Study Did not receive transplant	1

Baseline Characteristics

Allogeneic Hematopoietic Stem Cell Transplant For Epidermolysis Bullosa

Baseline characteristics by cohort

Measure	Epidermolysis Bullosa (EB) Patients n=7 Participants 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 .
Age, Categorical <=18 years	7 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	6.0 years STANDARD_DEVIATION 4.5 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants
Region of Enrollment United States	7 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 100 Post Transplant

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.

Outcome measures

Measure	Evaluable Patients n=6 Participants Includes only patients that received transplant (one patient died prior to transplant).
Number of Patients With Detectable Collagen Type VII	5 participants

SECONDARY outcome

Timeframe: Days 21, 100, 180, 365 and 730 Post Transplant

Number of patients with donor chimerism - percentage of donor cells in the patient via the peripheral blood or bone marrow.

Outcome measures

Measure	Evaluable Patients n=6 Participants Includes only patients that received transplant (one patient died prior to transplant).
Number of Patients With >70% Donor Chimerism Day 21	6 participants
Number of Patients With >70% Donor Chimerism Day 100	5 participants
Number of Patients With >70% Donor Chimerism Day 180	5 participants
Number of Patients With >70% Donor Chimerism Day 365	5 participants
Number of Patients With >70% Donor Chimerism Day 730	5 participants

SECONDARY outcome

Timeframe: Day 180 Post Transplant

Number of patients who died due to complications of the transplant (includes all deaths without previous relapse or progression).

Outcome measures

Measure	Evaluable Patients n=6 Participants Includes only patients that received transplant (one patient died prior to transplant).
Number of Patients With Transplant-Related Mortality	0 participants

SECONDARY outcome

Timeframe: Day 180 Post Transplant

Number of patients with a platelet count >5 x 10^10 cells/liter for 3 consecutive measurements.

Outcome measures

Measure	Evaluable Patients n=6 Participants Includes only patients that received transplant (one patient died prior to transplant).
Number of Patients With Platelet Engraftment	5 participants

SECONDARY outcome

Timeframe: Day 100 Post Transplant

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.

Outcome measures

Measure	Evaluable Patients n=6 Participants Includes only patients that received transplant (one patient died prior to transplant).
Number of Patients With Acute Graft-Versus-Host Disease (GVHD)	1 participants

SECONDARY outcome

Timeframe: Day 365 Post Transplant

Number of patients with cGVHD; a severe long-term complication created by infusion of donor cells into a foreign host.

Outcome measures

Measure	Evaluable Patients n=6 Participants Includes only patients that received transplant (one patient died prior to transplant).
Number of Patients With Chronic Graft-Versus-Host Disease (cGVHD)	0 participants

SECONDARY outcome

Timeframe: 1 year and 2 years Post Transplant

Survival is defined as the number of patients that were alive post transplant.

Outcome measures

Measure	Evaluable Patients n=6 Participants Includes only patients that received transplant (one patient died prior to transplant).
Overall Survival 1 Year Post Transplant	5 participants
Overall Survival 2 Years Post Transplant	5 participants

SECONDARY outcome

Timeframe: Day 90 Post Transplant

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).

Outcome measures

Measure	Evaluable Patients n=6 Participants Includes only patients that received transplant (one patient died prior to transplant).
Number of Patients With Donor Derived Cells in Skin	6 participants

SECONDARY outcome

Timeframe: Month 1 through Month 24 Inclusive

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

Resistance to Blister Formation demonstrated by response to negative pressure.

Outcome measures

Measure	Evaluable Patients n=2 Participants Includes only patients that received transplant (one patient died prior to transplant).
Number of Patients With Resistance to Blister Formation	2 participants

SECONDARY outcome

Timeframe: Day 42 Post Transplant

Number of patients with an absolute neutrophil count >5 x 10^8 cells/liter for 3 consecutive days.

Outcome measures

Measure	Evaluable Patients n=6 Participants Includes only patients that received transplant (one patient died prior to transplant).
Number of Patients With Neutrophil Engraftment	6 participants

Adverse Events

Epidermolysis Bullosa (EB) Patients

Serious events: 6 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Epidermolysis Bullosa (EB) Patients n=7 participants at risk 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 .
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	14.3% 1/7 • Number of events 1 • All subjects were monitored continuously and only serious unexpected and selected serious adverse experiences were collected during the first 100 days after cell infusion. 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.
Infections and infestations Bacterial infection	85.7% 6/7 • Number of events 6 • All subjects were monitored continuously and only serious unexpected and selected serious adverse experiences were collected during the first 100 days after cell infusion. 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.
General disorders Death	14.3% 1/7 • Number of events 1 • All subjects were monitored continuously and only serious unexpected and selected serious adverse experiences were collected during the first 100 days after cell infusion. 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.
Infections and infestations Fungal infection	28.6% 2/7 • Number of events 2 • All subjects were monitored continuously and only serious unexpected and selected serious adverse experiences were collected during the first 100 days after cell infusion. 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.
Skin and subcutaneous tissue disorders Grade IV skin toxicity	14.3% 1/7 • Number of events 1 • All subjects were monitored continuously and only serious unexpected and selected serious adverse experiences were collected during the first 100 days after cell infusion. 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.
Blood and lymphatic system disorders Graft failure	14.3% 1/7 • Number of events 1 • All subjects were monitored continuously and only serious unexpected and selected serious adverse experiences were collected during the first 100 days after cell infusion. 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.
Renal and urinary disorders Hemorrhagic cystitis	14.3% 1/7 • Number of events 1 • All subjects were monitored continuously and only serious unexpected and selected serious adverse experiences were collected during the first 100 days after cell infusion. 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.
Metabolism and nutrition disorders Hyperbilirubinemia	57.1% 4/7 • Number of events 4 • All subjects were monitored continuously and only serious unexpected and selected serious adverse experiences were collected during the first 100 days after cell infusion. 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.
Renal and urinary disorders Renal insufficiency	28.6% 2/7 • Number of events 2 • All subjects were monitored continuously and only serious unexpected and selected serious adverse experiences were collected during the first 100 days after cell infusion. 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.
Infections and infestations Viral infection	14.3% 1/7 • Number of events 4 • All subjects were monitored continuously and only serious unexpected and selected serious adverse experiences were collected during the first 100 days after cell infusion. 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.

Other adverse events

Adverse event data not reported

Additional Information

John E. Wagner, M.D.

Masonic Cancer Center, University of Minnesota

Phone: 612-626-2961

Email: wagne002@umn.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place