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 - Full Text View

Sponsored by:	Baylor College of Medicine
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00609258

Purpose

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.

Condition	Intervention	Phase
Precancerous/Nonmalignant Condition	Biological: alemtuzumab Biological: anti-CD45 monoclonal antibody Drug: fludarabine phosphate Procedure: allogeneic hematopoietic stem cell transplantation	Phase I

Study Type:	Interventional
Study Design:	Treatment, Open Label
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

Resource links provided by NLM:

Genetics Home Reference related topics: adenosine deaminase deficiency Wiskott-Aldrich syndrome X-linked severe combined immunodeficiency

Drug Information available for: Fludarabine Fludarabine monophosphate Campath Alemtuzumab Immunoglobulins Globulin, Immune

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

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 ]

Estimated Enrollment:	21
Study Start Date:	December 2007
Estimated Primary Completion Date:	December 2013 (Final data collection date for primary outcome measure)

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.

Eligibility

Ages Eligible for Study:	up to 17 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00609258

Locations

United States, Texas
Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital	Recruiting
Houston, Texas, United States, 77030-2399
Contact: Marlen Dinu 832-824-4881

Sponsors and Collaborators

Baylor College of Medicine

Investigators

Study Chair:

Robert Krance, MD

Baylor College of Medicine

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000582364, BCM-H-21123, BCM-MASCI
Study First Received:	January 30, 2008
Last Updated:	June 9, 2009
ClinicalTrials.gov Identifier:	NCT00609258 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

severe combined immunodeficiency
Wiskott-Aldrich syndrome

Study placed in the following topic categories:

Antimetabolites
Metabolic Diseases
Immunologic Factors
Precancerous Conditions
Severe Combined Immunodeficiency
Primary Immunodeficiency Disorders
Fludarabine monophosphate
Immunosuppressive Agents
Immunologic Deficiency Syndromes

Wiskott Aldrich Syndrome
Antibodies, Monoclonal
Wiskott-Aldrich Syndrome
Antibodies
Alemtuzumab
Infant, Newborn, Diseases
Fludarabine
Metabolic Disorder
Immunoglobulins

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Metabolic Diseases
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Precancerous Conditions
Immune System Diseases
Antineoplastic Agents
Severe Combined Immunodeficiency
Physiological Effects of Drugs
DNA Repair-Deficiency Disorders

Fludarabine monophosphate
Immunosuppressive Agents
Pharmacologic Actions
Immunologic Deficiency Syndromes
Antibodies, Monoclonal
Neoplasms
Antibodies
Therapeutic Uses
Alemtuzumab
Infant, Newborn, Diseases
Fludarabine

ClinicalTrials.gov processed this record on July 06, 2009