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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

Primary Purpose

Aplastic Anemia

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
cyclophosphamide
anti-thymocyte globulin
cyclosporine
allogeneic bone marrow transplantation
methotrexate
DNA analysis
flow cytometry
polymorphism analysis
laboratory biomarker analysis
Sponsored by
Fred Hutchinson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Aplastic Anemia

Eligibility Criteria

undefined - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Huntsman Cancer Institute/University of Utah
  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  • Froedtert and the Medical College of Wisconsin

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (conditioning regimen, transplant, GVHD prophylaxis)

Arm Description

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.

Outcomes

Primary Outcome Measures

Incidence of Chronic GVHD
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
First of 3 consecutive days of neutrophils >500/uL
Overall Survival
Number of patients alive at one year

Full Information

First Posted
June 22, 2006
Last Updated
March 16, 2017
Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
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1. Study Identification

Unique Protocol Identification Number
NCT00343785
Brief Title
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
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 Type
Interventional

2. Study Status

Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
February 2006 (undefined)
Primary Completion Date
May 2012 (Actual)
Study Completion Date
August 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aplastic Anemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (conditioning regimen, transplant, GVHD prophylaxis)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Other Intervention Name(s)
CPM, CTX, Cytoxan, Endoxan, Endoxana
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
anti-thymocyte globulin
Other Intervention Name(s)
ATG, ATGAM, lymphocyte immune globulin, Thymoglobulin
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
cyclosporine
Other Intervention Name(s)
ciclosporin, cyclosporin, cyclosporin A, CYSP, Sandimmune
Intervention Description
Given IV or PO
Intervention Type
Procedure
Intervention Name(s)
allogeneic bone marrow transplantation
Other Intervention Name(s)
bone marrow therapy, allogeneic, bone marrow therapy, allogenic, transplantation, allogeneic bone marrow, transplantation, allogenic bone marrow
Intervention Description
Undergo allogeneic bone marrow transplantation
Intervention Type
Drug
Intervention Name(s)
methotrexate
Other Intervention Name(s)
amethopterin, Folex, methylaminopterin, Mexate, MTX
Intervention Description
Given IV
Intervention Type
Genetic
Intervention Name(s)
DNA analysis
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
flow cytometry
Intervention Description
Correlative studies
Intervention Type
Genetic
Intervention Name(s)
polymorphism analysis
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Incidence of Chronic GVHD
Description
Analyzed using cumulative incidence estimates, treating death or rejection as competing risk events.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Number of Days to Neutrophil Recovery to >500/uL
Description
First of 3 consecutive days of neutrophils >500/uL
Time Frame
100 days post-transplant
Title
Overall Survival
Description
Number of patients alive at one year
Time Frame
From the time of enrollment until death from any cause up to one year

10. Eligibility

Sex
All
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rainer Storb
Organizational Affiliation
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Huntsman Cancer Institute/University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
Froedtert and the Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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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