| |
RATIONALE: Giving low doses of chemotherapy, such as cyclophosphamide, before a donor bone marrow transplant helps stop the growth of abnormal cells. It also stops the patient's immune system from rejecting the donor's bone marrow. The donated bone marrow stem cells may replace the patient's immune system and help destroy any remaining abnormal cells. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving a smaller than usual dose of bone marrow stem cells and giving antithymocyte globulin, cyclosporine and methotrexate before or after transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well giving cyclophosphamide together with antithymocyte globulin followed by methotrexate and cyclosporine works in preventing chronic graft-versus-host disease in patients with severe aplastic anemia undergoing a reduced-dose donor bone marrow transplant.
Graft Versus Host Disease Precancerous/Nonmalignant Condition
|
Drug: anti-thymocyte globulin Drug: cyclophosphamide Drug: cyclosporine Drug: methotrexate Procedure: allogeneic hematopoietic stem cell transplantation Procedure: bone marrow transplantation
|
Phase II
|
U.S. FDA Resources
| Study Type: |
Interventional |
| Study Design: |
Treatment, Open Label |
|
| Official Title: |
Cyclophosphamide and Antithymocyte Globulin Conditioning Regimen for Marrow Transplantation From HLA-Matched Family Members for Severe Aplastic Anemia: Effect of Marrow Cell Dose on Chronic Graft-vs.-Host Disease: A Multi-Center Trial |
Primary Outcome Measures:
- Incidence of chronic graft-versus-host-disease (GVHD) [ Designated as safety issue: No ]
- Correlate cell populations with incidence of chronic GVHD [ Designated as safety issue: No ]
- Marrow inocula content of natural killer cells, dendritic cells, CD34, CD20, CD14, CD4, CD3, CD8, and naïve and memory T cells [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Engraftment and overall survival at 100 days and annually thereafter [ Designated as safety issue: No ]
| Estimated Enrollment: |
150 |
| Study Start Date: |
February 2006 |
| Estimated Primary Completion Date: |
February 2011 (Final data collection date for primary outcome measure) |
OBJECTIVES:
Primary
- Minimize the incidence of chronic graft-versus-host disease (GVHD) by restricting the transplanted marrow dose in patients with severe aplastic anemia undergoing HLA-matched related bone marrow transplantation.
- Develop a better understanding of which cell subpopulations in the graft might contribute to chronic GVHD.
- Determine the content of natural killer cells, dendritic cells, CD34, CD20, CD14, CD4, CD3, CD8, and naïve and memory T cells in the marrow inocula.
Secondary
- Assess engraftment and overall survival of these patients.
OUTLINE: This is a multicenter study.
Patients receive cyclophosphamide IV over 1-2 hours on days -5 to -2 and antithymocyte globulin IV over 4-10 hours on days -4 to -2. Patients undergo an allogeneic reduced-dose bone marrow transplantation on day 0. Patients also receive methotrexate IV on days 1, 3, 6, and 11 and cyclosporine IV over 1 hour or orally twice daily on days -1 to 50, followed by a taper.
After completion of study treatment, patients are followed for 100 days and then annually thereafter.
PROJECTED ACCRUAL: A total of 150 patients will be accrued for this study.
| Ages Eligible for Study: |
up to 65 Years |
| Genders Eligible for Study: |
Both |
| Accepts Healthy Volunteers: |
No |
DISEASE CHARACTERISTICS:
-
Diagnosis of aplastic anemia with marrow failure, meeting 2 of the following criteria:
- Granulocyte count < 500/mm³
- Corrected reticulocyte count < 1%
- Platelet count < 20,000/mm³
-
No severe disease other than aplastic anemia that would severely limit the probability of survival during the graft procedure, including any of the following:
- Clonal cytogenetic abnormalities or myelodysplastic syndromes (preleukemia)
- Fanconi's anemia
- Aplasia secondary to radiotherapy or cytotoxic chemotherapy
- Paroxysmal nocturnal hemoglobinuria that has not developed into aplastic anemia
- HLA-matched family member available as a donor
PATIENT CHARACTERISTICS:
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No concurrent amphotericin B, antibodies, other investigational medications, or other blood products
Please refer to this study by its ClinicalTrials.gov identifier: NCT00343785
|
|
| Children's Hospital and Research Center Oakland |
|
|
| Oakland, California, United States, 94609 |
|
| Contact: Clinical Trial Office - Children's Hospital and Research Cente 510-450-7600 |
|
| City of Hope Comprehensive Cancer Center |
|
|
| Duarte, California, United States, 91010-3000 |
|
| Contact: Clinical Trials Office - City of Hope Comprehensive Cancer Cen 800-826-4673 becomingapatient@coh.org |
|
|
| Hackensack University Medical Center Cancer Center |
|
|
| Hackensack, New Jersey, United States, 07601 |
|
| Contact: Scott D. Rowley, MD, FACP 201-996-5900 |
|
|
| Oregon Health and Science University Cancer Institute |
|
|
| Portland, Oregon, United States, 97239-3098 |
|
| Contact: Clinical Trials Office - Oregon Health and Science University 503-494-1080 trials@ohsu.edu |
|
|
| Huntsman Cancer Institute at University of Utah |
|
|
| Salt Lake City, Utah, United States, 84112 |
|
| Contact: Michael A. Pulsipher, MD 801-585-3229 michael.pulsipher@hsc.utah.edu |
|
|
| Seattle Cancer Care Alliance |
|
|
| Seattle, Washington, United States, 98109-1023 |
|
| Contact: Clinical Trials Office - Seattle Cancer Care Alliance 800-804-8824 |
|
| Veterans Affairs Medical Center - Seattle |
|
|
| Seattle, Washington, United States, 98108 |
|
| Contact: Thomas R. Chauncey, MD, PhD 206-764-2709 |
|
|
| Medical College of Wisconsin Cancer Center |
|
|
| Milwaukee, Wisconsin, United States, 53226 |
|
| Contact: Clinical Trials Office - Medical College of Wisconsin Cancer C 414-805-4380 |
|
| Principal Investigator: |
Rainer F. Storb, MD |
Fred Hutchinson Cancer Research Center |
|
|
| Children's Hospital and Research Center Oakland |
|
|
| Oakland, California, United States, 94609 |
|
| Contact: Clinical Trial Office - Children's Hospital and Research Cente 510-450-7600 |
|
| City of Hope Comprehensive Cancer Center |
|
|
| Duarte, California, United States, 91010-3000 |
|
| Contact: Clinical Trials Office - City of Hope Comprehensive Cancer Cen 800-826-4673 becomingapatient@coh.org |
|
|
| Hackensack University Medical Center Cancer Center |
|
|
| Hackensack, New Jersey, United States, 07601 |
|
| Contact: Scott D. Rowley, MD, FACP 201-996-5900 |
|
|
| Oregon Health and Science University Cancer Institute |
|
|
| Portland, Oregon, United States, 97239-3098 |
|
| Contact: Clinical Trials Office - Oregon Health and Science University 503-494-1080 trials@ohsu.edu |
|
|
| Huntsman Cancer Institute at University of Utah |
|
|
| Salt Lake City, Utah, United States, 84112 |
|
| Contact: Michael A. Pulsipher, MD 801-585-3229 michael.pulsipher@hsc.utah.edu |
|
|
| Seattle Cancer Care Alliance |
|
|
| Seattle, Washington, United States, 98109-1023 |
|
| Contact: Clinical Trials Office - Seattle Cancer Care Alliance 800-804-8824 |
|
| Veterans Affairs Medical Center - Seattle |
|
|
| Seattle, Washington, United States, 98108 |
|
| Contact: Thomas R. Chauncey, MD, PhD 206-764-2709 |
|
|
| Medical College of Wisconsin Cancer Center |
|
|
| Milwaukee, Wisconsin, United States, 53226 |
|
| Contact: Clinical Trials Office - Medical College of Wisconsin Cancer C 414-805-4380 |
|
| Principal Investigator: |
Rainer F. Storb, MD |
Fred Hutchinson Cancer Research Center |
| Study ID Numbers: |
CDR0000480733, FHCRC-2054.00 |
| First Received: |
June 22, 2006 |
| Last Updated: |
May 23, 2008 |
| ClinicalTrials.gov Identifier: |
NCT00343785 |
| Health Authority: |
Unspecified |
Keywords provided by National Cancer Institute (NCI):
| graft versus host disease |
| aplastic anemia | |
Study placed in the following topic categories:
| Cyclosporine |
| Precancerous Conditions |
| Clotrimazole |
| Hematologic Diseases |
| Graft versus host disease |
| Miconazole |
| Tioconazole |
| Anemia |
| Cyclophosphamide | |
|
| Cyclosporins |
| Homologous wasting disease |
| Folic Acid |
| Antilymphocyte Serum |
| Anemia, Aplastic |
| Graft vs Host Disease |
| Methotrexate |
| Bone Marrow Diseases |
| Aplastic anemia | |
Additional relevant MeSH terms:
| Anemia, Aplastic |
| Antimetabolites |
| Anti-Infective Agents |
| Antimetabolites, Antineoplastic |
| Molecular Mechanisms of Pharmacological Action |
| Immunologic Factors |
| Antineoplastic Agents |
| Physiological Effects of Drugs |
| Reproductive Control Agents |
| Therapeutic Uses | |
|
| Antifungal Agents |
| Abortifacient Agents |
| Alkylating Agents |
| Dermatologic Agents |
| Nucleic Acid Synthesis Inhibitors |
| Immune System Diseases |
| Enzyme Inhibitors |
| Abortifacient Agents, Nonsteroidal |
| Folic Acid Antagonists |
| Immunosuppressive Agents | | Source: National Library of Medicine (NLM) July 09, 2008
|
|