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Cyclophosphamide, Antithymocyte Globulin, and Total-Body Irradiation in Treating Patients With Severe Aplastic Anemia Undergoing Umbilical Cord Blood Transplant

Primary Purpose

Aplastic Anemia

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
total-body irradiation
cyclophosphamide
anti-thymocyte globulin
cyclosporine
umbilical cord blood transplantation
mycophenolate mofetil
bone marrow aspiration
DNA analysis
filgrastim
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 - 40 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Life-threatening marrow failure of nonmalignant etiology meeting two of the three following criteria: granulocytes < 500/mm^3; a corrected reticulocyte count < 1%; platelet count < 20,000/mm^3 Failure to respond to the best available immunosuppressive treatment protocol by 75 days after initiation of therapy Lack of an HLA-identical family member or closely matched (9 or 10 of 10 HLA-locus match) unrelated marrow donor DONOR: Unrelated UCB unit matched for at least 4 of 6 loci DONOR: Related UCB unit matched for at least 3 of 6 lock Selection of the UCB unit(s) will be based upon matching or mismatching at HLA-A, B antigen level and DRB1 allele level typing; while HLA-C antigen/allele and HLA-DQB1 antigen/allele level typing are not considered in the matching criteria, if available each may be used to optimize unit selection Multiple UCB units are allowed to provide sufficient cell dose; when multiple units are selected, the following rules apply: a) the UCB unit with the least HLA disparity will be selected first (i.e., selection priority is 6/6 match > 5/6 match > 4/6 match), additional UCB units may be selected to increase cell dose; b) UCB units must be matched to each other for at least 4 of 6 loci; c) each unit must contain at least 1.5 x 10^7 Total Nucleated Cells per kg recipient weight; d) the total cell dose of the combined units must be at least 3.0 x 10^7 Total Nucleated Cells per kg recipient weight Exclusion Criteria: Severe disease other than aplastic anemia that would severely limit the probability of survival during the graft procedure; patients who present with active fungal infections must be treated to resolve this problem before beginning the conditioning regimen HIV seropositive patients Patients who have developed clonal cytogenetic abnormalities or a myelodysplastic syndrome (these patients will be considered in separate protocols for myelodysplastic syndrome, etc.) Patients with paroxysmal nocturnal hemoglobinuria or Fanconi anemia Patients > 40 years of age Related or unrelated cord blood units with < 1.5 x 10^7 Total Nucleated Cells per kg recipient weight Related or unrelated cord blood units without full testing and negative results for hepatitis A, B, C, HIV, HTLV-1, CMV viruses

Sites / Locations

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm I

Arm Description

See Detailed Description

Outcomes

Primary Outcome Measures

Toxicity

Secondary Outcome Measures

Engraftment

Full Information

First Posted
July 19, 2006
Last Updated
January 3, 2011
Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00354419
Brief Title
Cyclophosphamide, Antithymocyte Globulin, and Total-Body Irradiation in Treating Patients With Severe Aplastic Anemia Undergoing Umbilical Cord Blood Transplant
Official Title
A Dose Finding Study of Total Body Irradiation for Conditioning Patients With Severe Aplastic Anemia Transplanted With Umbilical Cord Blood
Study Type
Interventional

2. Study Status

Record Verification Date
January 2011
Overall Recruitment Status
Terminated
Why Stopped
Low accrual
Study Start Date
February 2006 (undefined)
Primary Completion Date
December 2010 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
RATIONALE: Giving chemotherapy and total-body irradiation before a donor umbilical cord blood stem cell transplant helps stop the growth of abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil before and after transplant may stop this from happening. PURPOSE: This phase I trial is studying the side effects and best dose of total-body irradiation when given together with cyclophosphamide and antithymocyte globulin in treating patients with severe aplastic anemia undergoing umbilical cord blood transplant.
Detailed Description
OBJECTIVES: I. The objective of this study is to determine the lowest dose of total body irradiation combined with cyclophosphamide and antithymocyte globulin that will achieve sustained engraftment in patients with severe aplastic anemia transplanted with unrelated umbilical cord blood. OUTLINE: This is a dose-escalation study of total-body irradiation (TBI). MYELOABLATIVE CONDITIONING REGIMEN: Patients receive cyclophosphamide IV on days -7 to -4, -6 to -3, or -5 to -2 and antithymocyte globulin IV on days -6 to -4, -5 to -3, or -4 to -2. TBI: Patients undergo TBI twice daily on days -3, -2, and/or -1. UMBILICAL CORD BLOOD TRANSPLANTATION (UCBT): Patients undergo UCBT on day 0. Patients receive filgrastim (G-CSF) IV or subcutaneously beginning on day 1 and continuing until blood counts recover. GRAFT-VS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive cyclosporine IV or orally (twice daily for patients >= 6 years of age or 3 times daily for patients < 6 years of age) on days -1 to +180 and mycophenolate mofetil IV or orally (twice daily for patients >= 50 kg or 3 times daily for patients < 50 kg) beginning 4 hours after UCBT and continuing until approximately day +0. After completion of study therapy, patients are followed periodically.

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 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm I
Arm Type
Experimental
Arm Description
See Detailed Description
Intervention Type
Radiation
Intervention Name(s)
total-body irradiation
Other Intervention Name(s)
TBI
Intervention Description
Undergo radiotherapy
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Other Intervention Name(s)
CPM, CTX, Cytoxan, Endoxan, Endoxana, Enduxan
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)
27-400, ciclosporin, cyclosporin, cyclosporin A, CYSP, Sandimmune
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
umbilical cord blood transplantation
Other Intervention Name(s)
cord blood transplantation, transplantation, umbilical cord blood, UCB transplantation
Intervention Description
Undergo transplantation
Intervention Type
Drug
Intervention Name(s)
mycophenolate mofetil
Other Intervention Name(s)
Cellcept, MMF
Intervention Description
Given IV or orally
Intervention Type
Procedure
Intervention Name(s)
bone marrow aspiration
Intervention Description
Correlative study
Intervention Type
Genetic
Intervention Name(s)
DNA analysis
Intervention Description
Correlative study
Intervention Type
Biological
Intervention Name(s)
filgrastim
Other Intervention Name(s)
G-CSF, granulocyte colony-stimulating factor, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor
Intervention Description
Given IV or SC
Primary Outcome Measure Information:
Title
Toxicity
Secondary Outcome Measure Information:
Title
Engraftment

10. Eligibility

Sex
All
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Life-threatening marrow failure of nonmalignant etiology meeting two of the three following criteria: granulocytes < 500/mm^3; a corrected reticulocyte count < 1%; platelet count < 20,000/mm^3 Failure to respond to the best available immunosuppressive treatment protocol by 75 days after initiation of therapy Lack of an HLA-identical family member or closely matched (9 or 10 of 10 HLA-locus match) unrelated marrow donor DONOR: Unrelated UCB unit matched for at least 4 of 6 loci DONOR: Related UCB unit matched for at least 3 of 6 lock Selection of the UCB unit(s) will be based upon matching or mismatching at HLA-A, B antigen level and DRB1 allele level typing; while HLA-C antigen/allele and HLA-DQB1 antigen/allele level typing are not considered in the matching criteria, if available each may be used to optimize unit selection Multiple UCB units are allowed to provide sufficient cell dose; when multiple units are selected, the following rules apply: a) the UCB unit with the least HLA disparity will be selected first (i.e., selection priority is 6/6 match > 5/6 match > 4/6 match), additional UCB units may be selected to increase cell dose; b) UCB units must be matched to each other for at least 4 of 6 loci; c) each unit must contain at least 1.5 x 10^7 Total Nucleated Cells per kg recipient weight; d) the total cell dose of the combined units must be at least 3.0 x 10^7 Total Nucleated Cells per kg recipient weight Exclusion Criteria: Severe disease other than aplastic anemia that would severely limit the probability of survival during the graft procedure; patients who present with active fungal infections must be treated to resolve this problem before beginning the conditioning regimen HIV seropositive patients Patients who have developed clonal cytogenetic abnormalities or a myelodysplastic syndrome (these patients will be considered in separate protocols for myelodysplastic syndrome, etc.) Patients with paroxysmal nocturnal hemoglobinuria or Fanconi anemia Patients > 40 years of age Related or unrelated cord blood units with < 1.5 x 10^7 Total Nucleated Cells per kg recipient weight Related or unrelated cord blood units without full testing and negative results for hepatitis A, B, C, HIV, HTLV-1, CMV viruses
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ann Woolfrey
Organizational Affiliation
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Cyclophosphamide, Antithymocyte Globulin, and Total-Body Irradiation in Treating Patients With Severe Aplastic Anemia Undergoing Umbilical Cord Blood Transplant

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