Combination Chemotherapy Followed By Donor Stem Cell Transplant in Treating Young Patients With Epidermolysis Bullosa at High Risk of Developing Squamous Cell Skin Cancer - Full Text View

Sponsored by:	Masonic Cancer Center, University of Minnesota
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00478244

Purpose

RATIONALE: Giving chemotherapy before a donor stem cell transplant helps stop the growth of abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine together with mycophenolate mofetil before, during, and after transplant may stop this from happening.

PURPOSE: This clinical trial is studying how well combination chemotherapy followed by donor stem cell transplant works in treating young patients with epidermolysis bullosa at high risk of developing squamous cell skin cancer.

Condition	Intervention
Non-Melanomatous Skin Cancer Precancerous/Nonmalignant Condition	Drug: busulfan Drug: cyclophosphamide Drug: cyclosporine Drug: fludarabine phosphate Drug: mycophenolate mofetil Procedure: allogeneic bone marrow transplantation Procedure: allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation Procedure: umbilical cord blood transplantation

Genetics Home Reference related topics: epidermolysis bullosa simplex

MedlinePlus related topics: Bone Marrow Transplantation Cancer Skin Cancer

Drug Information available for: Cyclophosphamide Fludarabine Fludarabine monophosphate Cyclosporin Cyclosporine Mycophenolate Mofetil Mycophenolate mofetil hydrochloride Busulfan

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Allogeneic Hematopoietic Cell Transplantation to Correct the Biochemical Defect and Create Tolerance to Donor Tissue in Subjects With Epidermolysis Bullosa

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Incidence of detectable donor-derived collagen type VII at day 100 [ Designated as safety issue: No ]

Secondary Outcome Measures:

Incidence of transplant-related mortality at day 180 [ Designated as safety issue: No ]
Incidence of chimerism at days 21, 100, 180, 365, and 730 [ Designated as safety issue: No ]
Incidence of neutrophil recovery at day 42 and platelet recovery at day 180 [ Designated as safety issue: No ]
Incidence of acute graft-versus-host disease (GVHD) at day 100 [ Designated as safety issue: No ]
Incidence of chronic GVHD at 1 year [ Designated as safety issue: No ]
Probability of overall survival and disease-free survival at 1 and 2 years [ Designated as safety issue: No ]
Incidence of donor skin-derived epidermal cell survival 90 days after epidermal cell transplant [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	April 2007

Detailed Description:

OBJECTIVES:

Primary

Estimate the incidence of detectable donor-derived collagen type VII at day 100 in younger patients with epidermolysis bullosa at high risk of developing squamous cell carcinoma of the skin treated with busulfan, cyclophosphamide, and fludarabine phosphate followed by allogeneic hematopoietic stem cell transplantation from a healthy, unaffected related donor.

Secondary

Determine the incidence of transplant-related mortality at day 180 in patients treated with this regimen.
Determine the incidence of chimerism at days 21, 100, 180, 365, and 730 in patients treated with this regimen.
Determine the incidence of neutrophil recovery at day 42 and platelet recovery at day 180 in patients treated with this regimen.
Determine the incidence of acute graft-versus-host disease (GVHD) grade II-IV and grade III-IV at day 100 in patients treated with this regimen.
Determine the incidence of chronic GVHD at 1 year in patients treated with this regimen.
Determine the probability of survival at 1 and 2 years in patients treated with this regimen.
Determine the incidence of donor skin-derived epidermal cell survival 90 days after epidermal cell transplant in the patient subpopulation for whom epidermal transplant is performed.

OUTLINE: This is an open-label, pilot study.

Conditioning regimen: Patients receive busulfan IV over 2 hours every 6 hours on days -9 to -4, fludarabine phosphate IV over 1 hour on days -5 to -3, and high-dose cyclophosphamide IV over 1 hour on days -5 to -2.
Stem cell transplantation: Patients undergo allogeneic hematopoietic stem cell transplantation (may include bone marrow, peripheral blood stem cells, or umbilical cord blood) on day 0.
Graft-vs-host disease prophylaxis: Patients receive cyclosporine IV over 2 hours or orally every 8 hours on days -3 to 180 and mycophenolate mofetil IV or orally on days -3 to 30.
Epidermal cell transplantation: Patients with confirmed chimerism at day 100, but with persistent evidence of epidermolysis bullosa, undergo donor-derived epidermal cell transplantation.

After completion of study treatment, patients are followed periodically for at least 5 years.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	up to 25 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of epidermolysis bullosa (EB)
- Documented collagen type VII deficiency by the following methods:
  - Antigenic mapping (LH7.2 antibody)
  - Ultrastructure analysis of anchoring fibrils
  - DNA mutation analysis
No squamous cell carcinoma of the skin
Healthy related hematopoietic stem cell donor available and meeting 1 of the following criteria:
- HLA-A, B, DRB1-identical sibling bone marrow and/or umbilical cord blood donor (first priority)
- HLA-A, B, DRB1-matched or partially matched related donor (second priority)
- Donor may be a carrier but must be unaffected by EB

PATIENT CHARACTERISTICS:

Lansky performance status 60-100%
Glomerular filtration rate > 60 mL/min
Bilirubin < 5 times upper limit of normal (ULN)
AST and ALT < 5 times ULN
Alkaline phosphatase < 5 times ULN
Oxygen saturation > 92%
LVEF ≥ 45%
No active infection at time of transplantation (including active infection with Aspergillus or other mold within the past 30 days)
No HIV positivity

PRIOR CONCURRENT THERAPY:

No prior transplantation with donor skin

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00478244

Locations

United States, Minnesota
Masonic Cancer Center at University of Minnesota	Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Clinical Trials Office - Masonic Cancer Center at University o 612-624-2620

Sponsors and Collaborators

Masonic Cancer Center, University of Minnesota

Investigators

Study Chair:

John E. Wagner, MD

Masonic Cancer Center, University of Minnesota

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000546620, UMN-MT2006-15, UMN-0702M01504
Study First Received:	May 23, 2007
Last Updated:	July 26, 2008
ClinicalTrials.gov Identifier:	NCT00478244
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

squamous cell carcinoma of the skin
epidermolysis bullosa

Study placed in the following topic categories:

Cyclosporine
Precancerous Conditions
Clotrimazole
Squamous cell carcinoma
Miconazole
Epidermolysis Bullosa
Cyclophosphamide
Cyclosporins
Carcinoma, squamous cell
Mycophenolate mofetil
Congenital Abnormalities
Skin Diseases, Genetic
Skin Diseases, Vesiculobullous

Skin Diseases
Skin Abnormalities
Tioconazole
Fludarabine monophosphate
Skin Neoplasms
Carcinoma
Epidermoid carcinoma
Epidermolysis bullosa
Genetic Diseases, Inborn
Busulfan
Fludarabine
Carcinoma, Squamous Cell

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Immunosuppressive Agents
Pharmacologic Actions

Neoplasms
Neoplasms by Site
Antifungal Agents
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Dermatologic Agents
Alkylating Agents

ClinicalTrials.gov processed this record on January 16, 2009