Search / Trial NCT00001476

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

Launched by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID) · Nov 3, 1999

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Trial Information

Current as of March 02, 2024

Completed

Keywords

Cd34+ Progenitor Retrovirus Leukapheresis Transduction Granulocytes Chronic Granulomatous Disease

Description

This is a Phase I/II clinical trial to determine the efficacy and safety of a method of ex vivo gene therapy to treat both X-linked gp91phox deficient Chronic Granulomatous Disease (CGD) and autosomal recessive p47phox deficient CGD. CGD is an inherited immune deficiency in which blood neutrophils and monocytes fail to produce superoxide and other antimicrobial oxidants, and patients get recurrent life-threatening infections. 30 CGD patients of either sex at least 5 years of age may be enrolled in addition to the 5 patients enrolled in the first phase of this trial. Patients less than 16 ye...

Gender

All

Eligibility criteria

  • INCLUSION CRITERIA:
  • 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).
  • EXCLUSION CRITERIA:
  • 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.
  • HIV antibody/antigen positive or hepatitis B, C antigen positive. (Exceptions to this exclusion may be made on a case by case basis in consultation with the Transfusion Medicine staff where severe bacterial or fungal infection is present).
  • 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.

Attachments

readout_NCT00001476_2024-03-02.pdf

4.5 MB

NCT00001476_study_protocol.pdf

4.5 MB

About company

The National Institute of Allergy and Infectious Diseases (NIAID, /ˈnaɪ.æd/) is one of the 27 institutes and centers that make up the National Institutes of Health (NIH), an agency of the United States Department of Health and Human Services (HHS). NIAID's mission is to conduct basic and applied research to better understand, treat, and prevent infectious, immunologic, and allergic diseases.

Contacts

JC

Jennifer Cobb

Immunology at National Institute of Allergy and Infectious Diseases (NIAID)

Locations

Bethesda, Maryland, United States

People applied

Timeline

First submit

Trial launched

Trial updated

Estimated completion

Not reported

Reviews (48)

4.6

All reviews come from applied patients

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Leslie Alexander
20 September 2023

Duis aute irure dolor in reprehenderit in voluptate velit esse cillum dolore eu fugiat nulla pariatur. Excepteur sint occaecat cupidatat non proident, sunt in culpa qui officia deserunt mollit anim id est laborum?

Michael Foster
20 September 2023

Duis aute irure dolor in reprehenderit in voluptate velit esse cillum dolore eu fugiat nulla pariatur. Excepteur sint occaecat cupidatat non proident, sunt in culpa qui officia deserunt mollit anim id est laborum?

Dries Vincent
20 September 2023

Duis aute irure dolor in reprehenderit in voluptate velit esse cillum dolore eu fugiat nulla pariatur. Excepteur sint occaecat cupidatat non proident, sunt in culpa qui officia deserunt mollit anim id est laborum?

Leslie Alexander
20 September 2023

Duis aute irure dolor in reprehenderit in voluptate velit esse cillum dolore eu fugiat nulla pariatur. Excepteur sint occaecat cupidatat non proident, sunt in culpa qui officia deserunt mollit anim id est laborum?

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