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

This study has been terminated.
(Low accrual)
Sponsor:
Collaborator:
Information provided by:
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00354419
First received: July 19, 2006
Last updated: January 3, 2011
Last verified: January 2011
  Purpose

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.


Condition Intervention Phase
Aplastic Anemia
Radiation: total-body irradiation
Drug: cyclophosphamide
Biological: anti-thymocyte globulin
Drug: cyclosporine
Procedure: umbilical cord blood transplantation
Drug: mycophenolate mofetil
Procedure: bone marrow aspiration
Genetic: DNA analysis
Biological: filgrastim
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Dose Finding Study of Total Body Irradiation for Conditioning Patients With Severe Aplastic Anemia Transplanted With Umbilical Cord Blood

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Toxicity [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Engraftment [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: February 2006
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
See Detailed Description
Radiation: total-body irradiation
Undergo radiotherapy
Other Name: TBI
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
  • Enduxan
Biological: anti-thymocyte globulin
Given IV
Other Names:
  • ATG
  • ATGAM
  • lymphocyte immune globulin
  • Thymoglobulin
Drug: cyclosporine
Given IV
Other Names:
  • 27-400
  • ciclosporin
  • cyclosporin
  • cyclosporin A
  • CYSP
  • Sandimmune
Procedure: umbilical cord blood transplantation
Undergo transplantation
Other Names:
  • cord blood transplantation
  • transplantation, umbilical cord blood
  • UCB transplantation
Drug: mycophenolate mofetil
Given IV or orally
Other Names:
  • Cellcept
  • MMF
Procedure: bone marrow aspiration
Correlative study
Genetic: DNA analysis
Correlative study
Biological: filgrastim
Given IV or SC
Other Names:
  • G-CSF
  • granulocyte colony-stimulating factor
  • Neupogen
  • r-metHuG-CSF
  • Recombinant Methionyl Human Granulocyte Colony Stimulating Factor

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.

  Eligibility

Ages Eligible for Study:   up to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00354419

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: Ann Woolfrey Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Woolfrey, Ann, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
ClinicalTrials.gov Identifier: NCT00354419     History of Changes
Other Study ID Numbers: 2030.00, NCI-2010-00191
Study First Received: July 19, 2006
Last Updated: January 3, 2011
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Anemia
Anemia, Aplastic
Bone Marrow Diseases
Hematologic Diseases
Antilymphocyte Serum
Cyclophosphamide
Cyclosporine
Cyclosporins
Lenograstim
Mycophenolate mofetil
Mycophenolic Acid
Adjuvants, Immunologic
Alkylating Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014