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| ID | Type | Description | Link |
|---|---|---|---|
| CDR0000546620 | Other Identifier | PDQ | |
| UMN-0702M01504 | Other Identifier | IRB, University of Minnesota |
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Competing studies
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RATIONALE: In animal models, stem cells have been shown to home to the skin and repair the biochemical and structural abnormalities associated with recessive dystrophic epidermolysis bullosa (RDEB) (collagen 7 deficiency).
PURPOSE: To determine the safety and effectiveness of stem cell infusion in the treatment of RDEB.
OBJECTIVES:
Primary
Secondary
After completion of study treatment, patients are followed periodically for at least 5 years.
PROJECTED ACCRUAL: 30 patients
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Epidermolysis Bullosa (EB) Patients | Experimental | Epidermolysis bullosa patients treated per study regimen with chemotherapy and stem cell transplant. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| busulfan | Drug | Day -9 through Day -6: 1.1 mg/kg if < 12 kg IV every 6 hours; 0.8 mg/kg if > 12 kg. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With Detectable Collagen Type VII | 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. | Day 100 Post Transplant |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With >70% Donor Chimerism | Number of patients with donor chimerism - percentage of donor cells in the patient via the peripheral blood or bone marrow. | Days 21, 100, 180, 365 and 730 Post Transplant |
| Number of Patients With Transplant-Related Mortality |
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Inclusion criteria:
Diagnosis of epidermolysis bullosa (EB)
Documented collagen type VII deficiency by:
Performance status: >50% Lansky; >50% Karnofsky
Adequate organ function
Healthy related hematopoietic stem cell donor available and meeting 1 of the following criteria:
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| John E. Wagner, MD | Masonic Cancer Center, University of Minnesota | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Masonic Cancer Center, University of Minnesota | Minneapolis | Minnesota | 55455 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20818854 | Derived | 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. |
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All subjects were registered with the BMT Biostatistical Support Group at the University of Minnesota.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 . |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 . |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Secondary | Number of Patients With >70% Donor Chimerism | Number of patients with donor chimerism - percentage of donor cells in the patient via the peripheral blood or bone marrow. | Posted | Number | participants | Days 21, 100, 180, 365 and 730 Post Transplant |
|
|
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 . |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| John E. Wagner, M.D. | Masonic Cancer Center, University of Minnesota | 612-626-2961 | wagne002@umn.edu |
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| ID | Term |
|---|---|
| D004820 | Epidermolysis Bullosa |
| D016108 | Epidermolysis Bullosa Dystrophica |
| ID | Term |
|---|---|
| D012868 | Skin Abnormalities |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D012873 | Skin Diseases, Genetic |
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| ID | Term |
|---|---|
| D002066 | Busulfan |
| D003520 | Cyclophosphamide |
| C042382 | fludarabine phosphate |
| C024352 | fludarabine |
| D016026 | Bone Marrow Transplantation |
| ID | Term |
|---|---|
| D002072 | Butylene Glycols |
| D006018 | Glycols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
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| cyclophosphamide | Drug | Day -5 through Day -2: 50 mg/kg IV over 120 min. |
|
|
| fludarabine phosphate | Drug | Day -5 through Day -3: 25 mg/m2 IV over 60 min. |
|
|
| hematopoietic bone marrow transplantation | Procedure | allogeneic bone marrow, peripheral stem cell or umbilical cord blood transplantation |
|
|
Number of patients who died due to complications of the transplant (includes all deaths without previous relapse or progression). |
| Day 180 Post Transplant |
| Number of Patients With Platelet Engraftment | Number of patients with a platelet count >5 x 10^10 cells/liter for 3 consecutive measurements. | Day 180 Post Transplant |
| Number of Patients With Acute Graft-Versus-Host Disease (GVHD) | 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. | Day 100 Post Transplant |
| Number of Patients With Chronic Graft-Versus-Host Disease (cGVHD) | Number of patients with cGVHD; a severe long-term complication created by infusion of donor cells into a foreign host. | Day 365 Post Transplant |
| Overall Survival | Survival is defined as the number of patients that were alive post transplant. | 1 year and 2 years Post Transplant |
| Number of Patients With Donor Derived Cells in Skin | 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). | Day 90 Post Transplant |
| Number of Patients With Resistance to Blister Formation | Resistance to Blister Formation demonstrated by response to negative pressure. | Month 1 through Month 24 Inclusive |
| Number of Patients With Neutrophil Engraftment | Number of patients with an absolute neutrophil count >5 x 10^8 cells/liter for 3 consecutive days. | Day 42 Post Transplant |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
| Secondary | Number of Patients With Transplant-Related Mortality | Number of patients who died due to complications of the transplant (includes all deaths without previous relapse or progression). | Posted | Number | participants | Day 180 Post Transplant |
|
|
|
| Secondary | Number of Patients With Platelet Engraftment | Number of patients with a platelet count >5 x 10^10 cells/liter for 3 consecutive measurements. | Posted | Number | participants | Day 180 Post Transplant |
|
|
|
| Secondary | Number of Patients With Acute Graft-Versus-Host Disease (GVHD) | 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. | Posted | Number | participants | Day 100 Post Transplant |
|
|
|
| Secondary | Number of Patients With Chronic Graft-Versus-Host Disease (cGVHD) | Number of patients with cGVHD; a severe long-term complication created by infusion of donor cells into a foreign host. | Posted | Number | participants | Day 365 Post Transplant |
|
|
|
| Secondary | Overall Survival | Survival is defined as the number of patients that were alive post transplant. | Posted | Number | participants | 1 year and 2 years Post Transplant |
|
|
|
| Secondary | Number of Patients With Donor Derived Cells in Skin | 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). | Posted | Number | participants | Day 90 Post Transplant |
|
|
|
| Secondary | Number of Patients With Resistance to Blister Formation | Resistance to Blister Formation demonstrated by response to negative pressure. | Added blister formation testing later in study; only 2 patients had pre-transplant test. | Posted | Number | participants | Month 1 through Month 24 Inclusive |
|
|
|
| Secondary | Number of Patients With Neutrophil Engraftment | Number of patients with an absolute neutrophil count >5 x 10^8 cells/liter for 3 consecutive days. | Posted | Number | participants | Day 42 Post Transplant |
|
|
|
| Primary | Number of Patients With Detectable Collagen Type VII | 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. | Posted | Number | participants | Day 100 Post Transplant |
|
|
|
| 6 |
| 7 |
| 0 |
| 7 |
| Bacterial infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Death | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Fungal infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment | Candida sepsis |
|
| Grade IV skin toxicity | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Graft failure | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hemorrhagic cystitis | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hyperbilirubinemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Renal insufficiency | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
|
| Viral infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
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| D030342 | Genetic Diseases, Inborn |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D012872 | Skin Diseases, Vesiculobullous |
| D003095 | Collagen Diseases |
| D003240 | Connective Tissue Diseases |
| D008698 |
| Mesylates |
| D000476 | Alkanesulfonates |
| D017738 | Alkanesulfonic Acids |
| D000473 | Alkanes |
| D006839 | Hydrocarbons, Acyclic |
| D006838 | Hydrocarbons |
| D013451 | Sulfonic Acids |
| D013456 | Sulfur Acids |
| D013457 | Sulfur Compounds |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D016378 | Tissue Transplantation |
| D064987 | Cell- and Tissue-Based Therapy |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D014180 | Transplantation |
| D013514 | Surgical Procedures, Operative |