OBJECTIVES:

I. Investigate the efficiency and safety of transducing the human CD18 DNA into filgrastim (G-CSF) mobilized, CD34 enriched peripheral blood repopulating cells from patients with a severe or moderate deficiency form of leukocyte adherence deficiency (LAD) by retrovirus-mediated gene transfer.

II. Investigate whether the human CD18 cDNA is expressed sufficiently to benefit patients with this disease.

III. Determine whether repeated infusions of transduced peripheral blood repopulating cells increase the number of surface CD11/CD18 positive cells in these patients.

IV. Determine the extent of long-term persistence of transduced peripheral blood repopulating cells in LAD patients not receiving prior myeloablation.

Condition	Treatment or Intervention	Phase
Leukocyte Adhesion Deficiency Syndrome	Drug: filgrastim  Drug: Retrovirus vector LgCD18	Phase I

Further Study Details: 

Expected Total Enrollment:  4

PROTOCOL OUTLINE:

Patients receive filgrastim (G-CSF) subcutaneously daily on days 1-5 with peripheral blood cell collections on days 4 and 5. Patients receive infusions of transduced CD34+ peripheral blood cells on day 8. Patients may be offered a second course of transduced peripheral blood cells for a total of 4 infusions.

Patients are followed monthly for one year and then annually for 4 years.

Ages Eligible for Study:  4 Years   -   65 Years,  Genders Eligible for Study:  Both

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Leukocyte adherence deficiency (LAD): Severe or moderate deficiency LAD disease confirmed by surface immunofluorescence of peripheral blood leukocytes of less than 10% normal

Measurable clinical disease in the form of at least one episode of life-threatening disease

Allogeneic bone marrow transplantation offered if HLA-matched sibling donor available

--Patient Characteristics--

Performance status: Karnofsky 60-100%

Hematopoietic: WBC greater than 2,000/mm3; Absolute neutrophil count greater than 1,000/mm3; Platelet count greater than 50,000/mm3; Prothrombin time and partial thromboplastin time less than 1.5 times upper limit of normal (ULN)

Hepatic: Bilirubin no greater than 2.5 mg/dL; SGOT and SGPT no greater than 5 times ULN; Alkaline phosphatase no greater than 2 times ULN

Renal: Creatinine clearance greater than 50 mL/min

Cardiovascular: Normal cardiac function

Pulmonary: No cardiorespiratory instability

Other: Triglycerides less than 400 mg/dL; Amylase no greater than 1.5 times ULN; HIV negative; No acute infection; Not pregnant or nursing; Fertile patients must use effective contraception

Study chairs or principal investigators

Dennis D. Hickstein,  Study Chair,  Children's Hospital and Medical Center - Seattle   

Study ID Numbers:  199/13939; CHMC-S-IRB-198-99-07; CHMC-S-DK47754; CHMC-S-HL54881; CHMC-S-IRB-207-9708; CHMC-S-IRB-216-00-07; FHCRC-981; NIH/ORDA-9707-204; UWASH-198-99-07; UWASH-207-9708
Record last reviewed:  May 2001
Last Updated:  October 13, 2004
Record first received:  October 18, 1999
ClinicalTrials.gov Identifier:  NCT00004470
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08