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

NCT00343785 | Completed Phase 2 Results DMC

• 3 other identifiers: 2054.00NCI-2010-01781P01HL036444
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 3

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

Conditions

Aplastic Anemia

Outcome Measures

Primary Outcomes (1)

• Incidence of Chronic GVHD

  Analyzed using cumulative incidence estimates, treating death or rejection as competing risk events.

  2 years

Secondary Outcomes (2)

• Number of Days to Neutrophil Recovery to >500/uL

  100 days post-transplant

• Overall Survival

  From the time of enrollment until death from any cause up to one year

Study Arms (1)

Treatment (conditioning regimen, transplant, GVHD prophylaxis)

EXPERIMENTAL

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.

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

Interventions

cyclophosphamide DRUG

Given IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana

Treatment (conditioning regimen, transplant, GVHD prophylaxis)

anti-thymocyte globulin BIOLOGICAL

Given IV

Also known as: ATG, ATGAM, lymphocyte immune globulin, Thymoglobulin

Treatment (conditioning regimen, transplant, GVHD prophylaxis)

cyclosporine DRUG

Given IV or PO

Also known as: ciclosporin, cyclosporin, cyclosporin A, CYSP, Sandimmune

Treatment (conditioning regimen, transplant, GVHD prophylaxis)

allogeneic bone marrow transplantation PROCEDURE

Undergo allogeneic bone marrow transplantation

Also known as: bone marrow therapy, allogeneic, bone marrow therapy, allogenic, transplantation, allogeneic bone marrow, transplantation, allogenic bone marrow

Treatment (conditioning regimen, transplant, GVHD prophylaxis)

methotrexate DRUG

Given IV

Also known as: amethopterin, Folex, methylaminopterin, Mexate, MTX

Treatment (conditioning regimen, transplant, GVHD prophylaxis)

DNA analysis GENETIC

Correlative studies

Treatment (conditioning regimen, transplant, GVHD prophylaxis)

flow cytometry OTHER

Correlative studies

Treatment (conditioning regimen, transplant, GVHD prophylaxis)

polymorphism analysis GENETIC

Correlative studies

Treatment (conditioning regimen, transplant, GVHD prophylaxis)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (conditioning regimen, transplant, GVHD prophylaxis)

Eligibility Criteria

• Age: Up to 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (3)

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Froedtert and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Anemia, Aplastic

Interventions

Cyclophosphamide; Antilymphocyte Serum; thymoglobulin; Cyclosporine; Transplantation; Methotrexate; merphos; Flow Cytometry; Amplified Fragment Length Polymorphism Analysis

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Surgical Procedures, Operative; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical; Investigative Techniques; DNA Fingerprinting; Genetic Techniques; Polymerase Chain Reaction; Nucleic Acid Amplification Techniques

Results Point of Contact

• Title: Dr. Rainer Storb, Director Transplantation Biology
• Organization: Fred Hutchinson Cancer Research Center

rstrob@fredhutch.org

2066676839

Study Officials

• Rainer Storb

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 22, 2006
• First Posted: June 23, 2006
• Study Start: February 1, 2006
• Primary Completion: May 1, 2012
• Study Completion: August 1, 2012
• Last Updated: April 13, 2017
• Results First Posted: March 16, 2017

Record last verified: 2017-03

Locations

US (3)