Twins Study of Gene Therapy for HIV Infection

Launched by NATIONAL HUMAN GENOME RESEARCH INSTITUTE (NHGRI) · Nov 3, 1999

Keywords

ClinConnect Summary

This phase I/II pilot study will evaluate the safety, relative survival, and potential efficacy of infusions of activated, genetically engineered, syngeneic CD4+ T lymphocytes obtained from HIV-1 seronegative identical twins. T cells from each seronegative twin will be obtained by apheresis, enriched for CD4+ cells, induced to polyclonal proliferation with anti-CD3 and rIL-2 stimulation, divided into aliquots which will then be individually transduced with a control retroviral vector and up to two additional retroviral vectors containing potentially therapeutic genes (antisense TAR and/or t...

Gender

ALL

Eligibility criteria

• INCLUSION CRITERIA:
• • An identical twin pair, one of whom is seropositive for HIV-1, the other twin seronegative, by standard ELISA and Western blot testing.
• • Patients with Kaposi's sarcoma limited to the skin and/or mucous membranes are eligible for this study, but must not have received any systemic therapy for
• • KS within 4 weeks prior to entry. The diagnosis of KS must have been confirmed by biopsy.
• • Free from serious psychological or emotional illness and able to provide written informed consent.
• • Anticipated survival greater than 3 months.
• • 18 years of age or older.
• • Treatment with FDA-approved and/or expanded access antiretroviral agent(s) for patients with baseline CD4 counts below 500 cells/mm(3). Patients with baseline CD4 counts above 500 cells/mm(3) are eligible to receive cell therapy on this protocol, but must be treated with antiretroviral therapy if evidence of significant and persistent viral activation occurs in association with a cell infusion. "Significant and persistent viral activation" is defined as a 50 percent or greater increase above baseline in any virologic parameter for at least 2 consecutive weeks.
• • Recipient's CD4 count greater than 50 cells/mm(3).
• • Recipient and Donor willing to have samples stored and undergo HLA testing.
• EXCLUSION CRITERIA (Donor and Recipient):
• • Lymphomas.
• • Unwillingness to comply with current NIH Clinical Center guidelines concerning appropriate notification of all current sexual partners of an individual regarding his or her HIV-1 positive sero-status and the risk of transmission of HIV-1 infection.
• • Recent history of substance abuse unless evidence is provided of an ongoing therapeutic intervention (i.e. medical therapy or counseling) to control such abuse.
• • Pregnant at entry or unwillingness to practice barrier birth control or abstinence during the study.
• • No experimental therapy within 4 weeks of study participation. Antiretroviral agents available on an FDA-sanctioned, expanded access basis are permitted.
• EXCLUSION CRITERIA (Donor):
• • Untreated or inadequately treated medical condition (e.g., cardiopulmonary disease, acute infection) which, in the judgement of the Principal Investigator, precludes apheresis.
• • Serologic positivity for Epstein Barr virus, Cytomegalovirus, Hepatitis B or Hepatitis C, if and only if the recipient twin tests seronegative for the corresponding virus.