Gene Therapy for Chronic Granulomatous Diseases - Long-term Follow-up

NCT00001476 | Completed Phase 1

• 2 other identifiers: 95013495-I-0134
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

This protocol will follow patients who participated in NIAID's study Gene Therapy Approach for Chronic Granulomatous Diseases (95-I-0134). No further gene therapy treatments will be given under this protocol. However, because gene therapy is a new technology and involves a permanent change in the genetic code of some cells, patients who have had this treatment require long-term health monitoring. Participants will be asked to provide updated address and telephone information and the names of two contact persons, such as siblings or friends. Patients will be seen about once a year at the NIH Clinical Center to provide an update on their health status and donate a small blood sample (about 2 teaspoons), which will be frozen and stored. If a patient acquires a serious illness, such as cancer, his or her stored blood will be tested; another of blood or tissue sample may also be requested for further study. If a patient develops a medical problem that is thought possibly to be related to gene therapy, the illness will be investigated. The annual follow-up visits will continue indefinitely or until the patient declines to continue participation. Participants may also agree to store some of their blood future research on chronic granulomatous diseases and other medical conditions. Stored samples may be labeled with a code, such as a number, that only the study team can link with the patient. Any identifying information about the patient will be kept confidential as is permitted by law.

Conditions

Chronic Granulomatous Disease; Communicable Disease

Keywords

CD34+ Progenitor; Retrovirus; Leukapheresis; Transduction; Granulocytes; Chronic Granulomatous Disease

Interventions

Gene Therapy Method for CGD DRUG

Isolex 300i Magnetic Cell Selector DEVICE

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female; if concurrent infection is present or there has been recent multiple relapse of infection with likely potential for additional relapse, then subjects may include minors 5 to 17 years of age and adults of any age; if no concurrent infection is present at enrollment then subjects must be adults of any age or minors 16-17 years of age.
• History of severe infections (two infections requiring hospitalization and intravenous antibiotics).
• Confirmed diagnosis of Chronic Granulomatous Disease as defined by less than 2 percent of normal oxidant production by all circulating neutrophils.
• Confirmed CGD genetic subtype of gp91(phox)-deficiency or p47(phox)-deficiency as defined by the absence or deficiency of the phox subunit protein using an antibody detection assay (western blot, ELISA, or flow cytometry) of patient granulocytes.
• Subjects without current active infection or recent multiple recurrence of infections must have adequate organ function as defined by renal function (creatinine less than or equal to 2 mg per dl; less than or equal to 2+ proteinuria); hepatic function (bilirubin less than or equal to 1.5 mg per dl; prothrombin time less than or equal to 1.3 x control); hematologic function (WBC greater than or equal to 2500 per mm(3); granulocytes greater than or equal to 1200 per mm(3); platelet greater than or equal to 100,000; hematocrit greater than or equal to 26).
• Successful mobilization as demonstrated by greater than or equal to 10 CD34+ cells per microliter in peripheral blood on the day of the planned apheresis.
• Must weigh at least 15 kg.
• If a female of childbearing potential, then the patient must have a negative serum pregnancy test within one week of beginning administration of combination flt3L and GM-CSF or single agent G-CSF. Both male and female must use a barrier or other effective form of contraception during marrow growth factor administration and for at least three months following the last reinfusion of the transduced CD34 + PBHP.
• Written informed consent, conforming to institutional guidelines obtained from patient (and/or parent or guardian if a minor).

You may not qualify if:

• Female patients who are pregnant or lactating as determined by history and/or positive pregnancy test.
• While patients may have an active infection under treatment and still be included in the study, patients are excluded who are in shock, manifested by severe hypotension (less than 100 systolic or less than 60 diastolic) or severe hypoxia requiring mechanical ventilation and piO(2) greater than 40 percent.
• Any condition which in the opinion of the attending physician or the Apheresis Unit staff contraindicates apheresis procedures, such as cardiovascular instability, severe anemia (hematocrit/hemoglobin below less than 26/8), in adequate venous access, and/or severe coagulation disorder. Patients with severe infection who have a hematocrit/hemoglobin below less than 26/8 and might benefit clinically from participation in this protocol may undergo apheresis at the discretion of the physician in charge of the Apheresis Unit. In that setting RBC transfusion may be used to raise the hematocrit/hemoglobin to a level safe for apheresis.
• Any condition which in the opinion of the principal investigator or the patient's primary physician contraindicates administration of bone marrow growth factors at the indicated doses, such as preexisting severe autoimmune vasculitis or other severe autoimmune inflammatory conditions where augmentation of immune responses or infiltration of granulocytes may exacerbate the condition.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Malech HL, Maples PB, Whiting-Theobald N, Linton GF, Sekhsaria S, Vowells SJ, Li F, Miller JA, DeCarlo E, Holland SM, Leitman SF, Carter CS, Butz RE, Read EJ, Fleisher TA, Schneiderman RD, Van Epps DE, Spratt SK, Maack CA, Rokovich JA, Cohen LK, Gallin JI. Prolonged production of NADPH oxidase-corrected granulocytes after gene therapy of chronic granulomatous disease. Proc Natl Acad Sci U S A. 1997 Oct 28;94(22):12133-8. doi: 10.1073/pnas.94.22.12133.

  PMID: 9342375 BACKGROUND

• Sekhsaria S, Gallin JI, Linton GF, Mallory RM, Mulligan RC, Malech HL. Peripheral blood progenitors as a target for genetic correction of p47phox-deficient chronic granulomatous disease. Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7446-50. doi: 10.1073/pnas.90.16.7446.

  PMID: 8395049 BACKGROUND

• Li F, Linton GF, Sekhsaria S, Whiting-Theobald N, Katkin JP, Gallin JI, Malech HL. CD34+ peripheral blood progenitors as a target for genetic correction of the two flavocytochrome b558 defective forms of chronic granulomatous disease. Blood. 1994 Jul 1;84(1):53-8.

  PMID: 7517218 BACKGROUND

MeSH Terms

Conditions

Granulomatous Disease, Chronic; Communicable Diseases

Condition Hierarchy (Ancestors)

Phagocyte Bactericidal Dysfunction; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infections

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: June 1, 1995
• Primary Completion: December 13, 2010
• Study Completion: December 13, 2010
• Last Updated: July 2, 2017

Record last verified: 2010-12-13

Locations

US (1)