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Anti-CD45 Monoclonal Antibody, Alemtuzumab, and Fludarabine Followed By Donor Stem Cell Transplant in Treating Children With Severe Combined Immunodeficiency Disease or Other Primary Immunodeficiency Disorder

This study is currently recruiting participants.
Study NCT00609258.   Last updated on October 8, 2008.   Information provided by National Cancer Institute (NCI)

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Descriptive Information Fields
Brief Title  Anti-CD45 Monoclonal Antibody, Alemtuzumab, and Fludarabine Followed By Donor Stem Cell Transplant in Treating Children With Severe Combined Immunodeficiency Disease or Other Primary Immunodeficiency Disorder
Official Title  CD45 (YTH-24 and YTH 54) and Alemtuzumab (CamPath-1H) Monoclonal Antibody Conditioning Regimen for Allogeneic Donor Stem Cell Transplantation of Patients With Severe Combined Immunodeficiency Disease and Other Primary Immunodeficiency Disorders
Brief Summary

RATIONALE: Giving monoclonal antibodies, such anti-CD45 monoclonal antibody and alemtuzumab, and chemotherapy drugs, such as fludarabine, before a donor stem cell transplant 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.

PURPOSE: This phase I trial is studying the side effects and how well giving anti-CD45 monoclonal antibody together with alemtuzumab and fludarabine followed by donor stem cell transplant works in treating patients with severe combined immunodeficiency disease or other primary immunodeficiency disorder.

Detailed Description

OBJECTIVES:

  • To investigate whether anti-CD45 monoclonal antibody, alemtuzumab, and fludarabine followed by allogeneic stem cell transplantation using CD34+ selected cells promotes donor stem cell engraftment sufficient to provide T-cell function and B-cell function and to establish donor hematopoiesis in pediatric patients with severe combined immunodeficiency disease or other primary immunodeficiency disorder.
  • To investigate whether this treatment regimen can be given with minimal and acceptable short term toxicity.
  • To investigate the incidence of grade III-IV acute graft-versus-host disease in patients treated with this regimen.
  • To estimate the 1-year survival of patients treated with this regimen.

OUTLINE: Patients receive alemtuzumab IV on days -8 to -6, fludarabine IV on days -8 to -4, and anti-CD45 monoclonal antibody IV over 6 hours on days -5 to -2. Patients undergo allogeneic stem cell transplantation on day 0.

After completion of study treatment, patients are followed periodically.

Study Phase Phase I
Study Type  Interventional
Study Design  Treatment, Open Label
Primary Outcome Measure  T-cell function [ Designated as safety issue: No ]
B-cell function [ Designated as safety issue: No ]
Donor hematopoiesis [ Designated as safety issue: No ]
Toxicity [ Designated as safety issue: Yes ]
Incidence of grade III-IV acute graft-versus-host disease [ Designated as safety issue: Yes ]
1-year survival rate [ Designated as safety issue: No ]
Secondary Outcome Measure 
Condition  Precancerous/Nonmalignant Condition
Intervention  Drug: alemtuzumab
Drug: anti-CD45 monoclonal antibody
Drug: fludarabine phosphate
Procedure: allogeneic hematopoietic stem cell transplantation
MEDLINE PMIDs
Links Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site
Recruitment Information Fields
Recruitment Status  Recruiting
Enrollment  21
Start Date  December 2007
Completion Date
Eligibility Criteria 

DISEASE CHARACTERISTICS:

  • Diagnosis of one of the following:

    • Severe combined immunodeficiency disease (SCID), including SCID characterized by gene-specific mutations as well as clinical SCID without a defined genetic cause
    • Other severe primary immunodeficiency disorder, including any of the following:

      • Undefined T-cell deficiency disorder
      • Wiskott-Aldrich syndrome
      • Other severe immunodeficiencies for which satisfactory conventional therapy does not exist
  • HLA mismatched (up to one haplotype) related donor OR HLA matched or mismatched (up to one antigen) unrelated donor available

    • No HLA matched related donor available

PATIENT CHARACTERISTICS:

  • Lansky performance status (PS) or Karnofsky PS 70-100%
  • Life expectancy > 6 weeks
  • Creatinine ≤ 3 times normal for age
  • HIV negative
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No symptomatic cardiac disease
  • No evidence of significant cardiac disease by echocardiogram (i.e., shortening fraction < 25%)
  • No known allergy to rat serum products
  • No severe infection that, on evaluation by the Principal Investigator, precludes ablative chemotherapy or successful transplantation
  • No severe personality disorder or mental illness

PRIOR CONCURRENT THERAPY:

  • Not specified
Gender Both
Ages up to 17 Years
Accepts Healthy Volunteers No
Contacts ††
Location Countries  United States
Administrative Information Fields
NCT ID  NCT00609258
Organization ID CDR0000582364
Secondary IDs †† BCM-H-21123, BCM-MASCI
Study Sponsor  Baylor College of Medicine
Collaborators ††
Investigators 
Study Chair:     Robert Krance, MD     Baylor College of Medicine    
Information Provided By National Cancer Institute (NCI)
Verification Date April 2008
First Received Date  January 30, 2008
Last Updated Date October 8, 2008

 †    Required WHO trial registration data element.
††   WHO trial registration data element that is required only if it exists.




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