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
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.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Toxicity
Secondary Outcome
Engraftment
Condition
Aplastic Anemia
Intervention
total-body irradiation
Study Arms / Comparison Groups
Arm I
Description: See Detailed Description
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Radiation
Estimated Enrollment
30
Start Date
February 2006
Primary Completion Date
December 2010
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
Gender
All
Ages
N/A - 40 Years
Accepts Healthy Volunteers
No
Contacts
Ann Woolfrey, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00354419
Organization ID
2030.00
Secondary IDs
NCI-2010-00191
Study Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Ann Woolfrey, Principal Investigator, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Verification Date
January 2011