Gene Therapy for Patients With Leukocyte Adherence Deficiency (Follow-Up of Phase 1 Trial)

Follow-Up of a Phase-I Gene Therapy Trial of Patients With Leukocyte Adherence Deficiency

This study will provide long-term monitoring of two patients who received gene therapy for leukocyte adherence deficiency (LAD) under the Food and Drug Administration investigational new drug study BB-IND-7949. The IND protocol has been closed. No other patients are eligible for this study.

Patients previously enrolled in BB-IND-7949 (Retrovirus-Mediated Transfer of the cDNA for Human CD18 into Peripheral Blood Repopulating cells of Patients with Leukocyte Adherence Deficiency) will be followed at least yearly for an indefinite period of time to evaluate their medical status and look for treatment side effects. The follow-up visits at the NIH Clinical Center will involve the following:

• Interview regarding health status during the past year
• Blood draw of approximately 15 milliliters for 3 years, then 5 ml annually thereafter for studies related to LAD and to make sure no unexpected effects of gene therapy have occurred

The blood samples collected at the follow-up visits will be frozen and stored. If a serious medical problem arises, the sample may be checked for replication competent virus. If the gene therapy is suspected to be related to a medical problem, investigation may include a review of the patient's medical records or collection of additional blood or tissues for testing. If the patient should die, the family will be asked permission to perform an autopsy, regardless of the cause of death. Tissues taken at autopsy will be tested for any long-term effects from the gene therapy.

Study Overview

• Status: Completed
• Conditions: Leukocyte Adhesion Deficiency Syndrome

Detailed Description

Patients with leukocyte adhesion deficiency or LAD have a deficiency of the leukocyte integrin CD18 on their leukocyte cell surface and suffer from severe bacterial infections. Two patients with LAD were enrolled in a Phase I clinical trial conducted at the University of Washington School of Medicine in 1999 to determine the safety and potential efficacy of using retroviral vectors containing CD18 to transduce and correct their CD34+ peripheral blood stem cells. This protocol aims to continue the long-term follow-up of these patients at the National Cancer Institute where Dr. Hickstein is now a Senior Investigator. Blood samples will be collected at the follow-up visits on the yearly anniversary of the treatment date (either locally or off-site by the patients' personal physicians) for archiving for potential testing for replication competent retrovirus, and for complete blood counts. Patients will also undergo a history and physical examination at these visits. Results from these tests will be forwarded to the investigators who will report to the NIH and FDA.

• Study Type: Observational
• Enrollment (Actual): 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center, 9000 Rockville Pike

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

• Two patients treated under FDA IND BB-IND-7949.

Study Plan

How is the study designed?

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Anderson DC, Springer TA. Leukocyte adhesion deficiency: an inherited defect in the Mac-1, LFA-1, and p150,95 glycoproteins. Annu Rev Med. 1987;38:175-94. doi: 10.1146/annurev.me.38.020187.001135.
• Anderson DC, Schmalsteig FC, Finegold MJ, Hughes BJ, Rothlein R, Miller LJ, Kohl S, Tosi MF, Jacobs RL, Waldrop TC, et al. The severe and moderate phenotypes of heritable Mac-1, LFA-1 deficiency: their quantitative definition and relation to leukocyte dysfunction and clinical features. J Infect Dis. 1985 Oct;152(4):668-89. doi: 10.1093/infdis/152.4.668.

Study record dates

Study Major Dates

• Study Start: August 15, 2001
• Study Completion: December 13, 2010

Study Registration Dates

• First Submitted: August 18, 2001
• First Submitted That Met QC Criteria: August 18, 2001
• First Posted (Estimate): August 20, 2001

Study Record Updates

• Last Update Posted (Actual): July 2, 2017
• Last Update Submitted That Met QC Criteria: June 30, 2017
• Last Verified: December 13, 2010

More Information

Terms related to this study

• Keywords: Retrovirus; Stem Cell; Leukocyte Adhesion Deficiency; Gene Transfer; LAD; RCR; CD18
• Additional Relevant MeSH Terms: Pathologic Processes; Immunologic Deficiency Syndromes; Immune System Diseases; Genetic Diseases, Inborn; Fibrosis; Cicatrix; Primary Immunodeficiency Diseases; Tissue Adhesions; Leukocyte-Adhesion Deficiency Syndrome
• Other Study ID Numbers: 010236; 01-C-0236