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

January 3, 2011 updated by: Fred Hutchinson Cancer Center

A Dose Finding Study of Total Body Irradiation for Conditioning Patients With Severe Aplastic Anemia Transplanted With Umbilical Cord Blood

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 40 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm I
See Detailed Description
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • Endoxan
  • CPM
  • CTX
  • Endoxana
  • Enduxan
Biological: filgrastim
Given IV or SC
Other Names:
  • G-CSF
  • r-metHuG-CSF
  • Neupogen
  • Recombinant Methionyl Human Granulocyte Colony Stimulating Factor
  • granulocyte colony-stimulating factor
Procedure: bone marrow aspiration
Correlative study
Biological: anti-thymocyte globulin
Given IV
Other Names:
  • ATGAM
  • ATG
  • Thymoglobulin
  • lymphocyte immune globulin
Drug: cyclosporine
Given IV
Other Names:
  • 27-400
  • ciclosporin
  • cyclosporin
  • cyclosporin A
  • CYSP
  • Sandimmune
Radiation: total-body irradiation
Undergo radiotherapy
Other Names:
  • TBI
Procedure: umbilical cord blood transplantation
Undergo transplantation
Other Names:
  • UCB transplantation
  • cord blood transplantation
  • transplantation, umbilical cord blood
Drug: mycophenolate mofetil
Given IV or orally
Other Names:
  • Cellcept
  • MMF
Genetic: DNA analysis
Correlative study

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Toxicity

Secondary Outcome Measures

Outcome Measure
Engraftment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fred Hutchinson Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Ann Woolfrey, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2006

Primary Completion (Actual)

December 1, 2010

Study Registration Dates

First Submitted

July 19, 2006

First Submitted That Met QC Criteria

July 19, 2006

First Posted (Estimate)

July 20, 2006

Study Record Updates

Last Update Posted (Estimate)

January 5, 2011

Last Update Submitted That Met QC Criteria

January 3, 2011

Last Verified

January 1, 2011

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2030.00
  • NCI-2010-00191

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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