Cyclophosphamide and Anti-thymocyte Globulin Followed By Methotrexate and Cyclosporine in Preventing Chronic Graft-Versus-Host Disease in Patients With Severe Aplastic Anemia Undergoing Donor Bone Marrow Transplant
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| ClinicalTrials.gov Identifier: NCT00343785 |
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Recruitment Status :
Completed
First Posted : June 23, 2006
Results First Posted : March 16, 2017
Last Update Posted : April 13, 2017
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Sponsor:
Fred Hutchinson Cancer Research Center
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Rainer Storb, Fred Hutchinson Cancer Research Center
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Brief Summary:
This clinical trial is studying how well giving cyclophosphamide together with anti-thymocyte globulin followed by methotrexate and cyclosporine works in preventing chronic graft-vs-host disease (GVHD) in patients with severe aplastic anemia undergoing donor bone marrow transplant. 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 stem cells. The donated 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 anti-thymocyte globulin before and methotrexate and cyclosporine after transplant may stop this from happening
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Aplastic Anemia | Drug: cyclophosphamide Biological: anti-thymocyte globulin Drug: cyclosporine Procedure: allogeneic bone marrow transplantation Drug: methotrexate Genetic: DNA analysis Other: flow cytometry Genetic: polymorphism analysis Other: laboratory biomarker analysis | Phase 2 |
PRIMARY OBJECTIVES:
I. Minimize the incidence of chronic GVHD by restricting the transplanted marrow dose to 2.0-2.5 x 10^8 nucleated cells/kg.
SECONDARY OBJECTIVES:
I. Engraftment and overall survival.
OUTLINE:
CONDITIONING REGIMEN: Patients receive cyclophosphamide intravenously (IV) on days -5 to -2 and anti-thymocyte globulin IV over 4-10 hours on days -4 to -2.
TRANSPLANTATION: Patients undergo allogeneic bone marrow transplantation on day 0.
GVHD PROPHYLAXIS: Patients receive methotrexate IV on days 1, 3, 6, and 11 and cyclosporine IV over 1 hour or orally (PO) twice daily on days -1 to 50, followed by a taper until 6 months after grafting.
After completion of study treatment, patients are followed up at on day 180, 1 year, 1.5 years, 2 years, 3 years, and yearly thereafter.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 21 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Study Start Date : | February 2006 |
| Actual Primary Completion Date : | May 2012 |
| Actual Study Completion Date : | August 2012 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Treatment (conditioning regimen, transplant, GVHD prophylaxis)
Patients receive a conditioning regimen comprising cyclophosphamide IV on days -5 to -2 and anti-thymocyte globulin IV over 4-10 hours on days -4 to -2. Patients undergo allogeneic bone marrow transplantation on day 0. Patients then receive GVHD prophylaxis comprising methotrexate IV on days 1, 3, 6, and 11 and cyclosporine IV over 1 hour or PO twice daily on days -1 to 50, followed by a taper until 6 months after grafting.
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Drug: cyclophosphamide
Given IV
Other Names:
Biological: anti-thymocyte globulin Given IV
Other Names:
Drug: cyclosporine Given IV or PO
Other Names:
Procedure: allogeneic bone marrow transplantation Undergo allogeneic bone marrow transplantation
Other Names:
Drug: methotrexate Given IV
Other Names:
Genetic: DNA analysis Correlative studies Other: flow cytometry Correlative studies Genetic: polymorphism analysis Correlative studies Other: laboratory biomarker analysis Correlative studies |
Primary Outcome Measures :
- Incidence of Chronic GVHD [ Time Frame: 2 years ]Analyzed using cumulative incidence estimates, treating death or rejection as competing risk events.
Secondary Outcome Measures :
- Number of Days to Neutrophil Recovery to >500/uL [ Time Frame: 100 days post-transplant ]First of 3 consecutive days of neutrophils >500/uL
- Overall Survival [ Time Frame: From the time of enrollment until death from any cause up to one year ]Number of patients alive at one year
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| Ages Eligible for Study: | up to 65 Years (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Any patient who has aplastic anemia with marrow failure involving 2 of the three following criteria: granulocytes < 500/uL; a corrected reticulocyte count of < 1%; platelet count of < 20,000/uL
- Availability of an human leukocyte antigen (HLA)-matched family member
- DONOR: Family member who is HLA-matched
- DONOR: If more than one HLA-matched family member is available, priority will be given to a donor who is genotypically HLA-identical, of appropriate cytomegalovirus (CMV) serology, ABO compatible, and, in case of a female donor, non-parous
Exclusion Criteria:
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Severe disease other than aplastic anemia that would severely limit the probability of survival during the graft procedure:
- Patients who have developed clonal cytogenetic abnormalities or myelodysplastic syndrome (preleukemia)
- Patients with Fanconi's anemia
- Aplasia secondary to radiation or cytotoxic chemotherapy
- Patients with paroxysmal nocturnal hemoglobinuria who have not developed aplastic anemia
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Severe organ toxicities:
- Cardiac insufficiency requiring treatment or symptomatic coronary artery disease;
- Severe hypoxemia , partial pressure of oxygen (pO2) < 70 mm Hg, with decreased diffusion capacity of carbon monoxide (DLCO) < 70% of predicted; or mild hypoxemia, pO2 < 80 mm Hg with severely decreased DLCO < 60% of predicted;
- Impaired renal function (creatinine > 2 times upper limit of normal or estimated creatinine clearance < 60 ml/min)
- Fungal infections with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month
- Human immunodeficiency virus (HIV)-positive patients
- Females who are pregnant or breast-feeding
- DONOR: Donors who have increase anesthetic risk and are not able psychologically and medically to tolerate the procedure
- DONOR: HIV-positive donors
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00343785
Locations
| United States, Utah | |
| Huntsman Cancer Institute/University of Utah | |
| Salt Lake City, Utah, United States, 84112 | |
| United States, Washington | |
| Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | |
| Seattle, Washington, United States, 98109 | |
| United States, Wisconsin | |
| Froedtert and the Medical College of Wisconsin | |
| Milwaukee, Wisconsin, United States, 53226 | |
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
| Principal Investigator: | Rainer Storb | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium |
| Responsible Party: | Rainer Storb, Principal Investigator, Fred Hutchinson Cancer Research Center |
| ClinicalTrials.gov Identifier: | NCT00343785 |
| Other Study ID Numbers: |
2054.00 NCI-2010-01781 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) P01HL036444 ( U.S. NIH Grant/Contract ) |
| First Posted: | June 23, 2006 Key Record Dates |
| Results First Posted: | March 16, 2017 |
| Last Update Posted: | April 13, 2017 |
| Last Verified: | March 2017 |
Additional relevant MeSH terms:
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Anemia Anemia, Aplastic Hematologic Diseases Bone Marrow Diseases Cyclosporine Cyclophosphamide Methotrexate Cyclosporins Thymoglobulin Antilymphocyte Serum Immunoglobulins Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents |
Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Abortifacient Agents, Nonsteroidal Abortifacient Agents Reproductive Control Agents Antimetabolites, Antineoplastic Antimetabolites Dermatologic Agents Enzyme Inhibitors Folic Acid Antagonists Nucleic Acid Synthesis Inhibitors Antifungal Agents |