Clinical trial NCT00023010: Gene Therapy for Patients With Leukocyte Adherence Deficiency (Follow-Up of Phase 1 Trial)
Official title: Follow-Up of a Phase-I Gene Therapy Trial of Patients With Leukocyte Adherence Deficiency
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Leukocyte Adhesion Deficiency Syndrome
Keywords: CD18
Retrovirus
RCR
Stem Cell
Gene Transfer
Leukocyte Adhesion Deficiency
LAD
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2001-08-20
Enrollment: 2
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no

Brief summary: 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.

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.

Eligibility criteria: * Two patients treated under FDA IND BB-IND-7949.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center, 9000 Rockville Pike
state: Maryland
Study officials:
References:
citation: 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.
citation: 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.