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

Aplastic Anemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00343785
• Other study ID #: 2054.00
• Secondary ID: NCI-2010-01781P0
• Status: Completed
• Phase: Phase 2
• First received: June 22, 2006
• Last updated: September 18, 2012
• Start date: February 2006

Study information

• Verified date: September 2012
• Source: Fred Hutchinson Cancer Research Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 65 Years

Eligibility

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:

• 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

• 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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia
• Anemia, Aplastic
• Aplastic Anemia

Intervention

Drug:
• cyclophosphamide
Given IV

Biological:
• anti-thymocyte globulin
Given IV

Drug:
• cyclosporine
Given IV or PO

Procedure:
• allogeneic bone marrow transplantation
Undergo allogeneic bone marrow transplantation

Drug:
• methotrexate
Given IV

Genetic:
• DNA analysis
Correlative studies

Other:
• flow cytometry
Correlative studies

Genetic:
• polymorphism analysis
Correlative studies

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	Froedtert and the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of chronic GVHD	Analyzed using cumulative incidence estimates, treating death or rejection as competing risk events. Confidence intervals will be calculated using the method described by Marubini and Valsecchi (1995). Risk factors for the development of chronic GVHD will be evaluated using Cox regression analyses methods.	2 years	No
Secondary	Engraftment		100 days post-transplant	No
Secondary	Overall survival		From the time of enrollment until death from any cause, assessed up to approximately 6 years	No