Genetically Modified Lymphocytes to Treat HIV-Infected Identical Twins - Study Modifications

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00001409
First received: November 3, 1999
Last updated: March 3, 2008
Last verified: June 2002
  Purpose

Certain patients enrolled in NIH protocol 94-I-0206 at the Clinical Center may be eligible to participate in one or more of the following new options:

  • Donor/recipient extension phase - Both the recipient (HIV-infected twin) and donor (non-infected twin) will participate in this extension of the CD4-zeta gene therapy study. It will evaluate the safety and activity of infusing gene-modified CD4+ cells as well as the modified CD8+ cells.
  • Corticosteroid administration - A corticosteroid, such as prednisone, hydrocortisone or prednisolone, will be added to the interleukin-2 (IL-2) regimen for preventing or treating side effects of IL-2 such as fever and other flu-like symptoms.
  • Extended follow-up - A more intensive follow-up will be scheduled for patients with substantial numbers of lymphocytes that harbor the CD4-zeta gene. Every 3 months, participants will have blood tests and specialized tests of CD4 counts, HIV-1 viral load and numbers of circulating cells containing the CD4-zeta gene every 3 months> the frequency of follow-up visits may be reduced as time goes by.
  • IL-2 continuation - Participants will continue to receive periodic treatment with IL-2 to see how long the genetically modified cells persist in the bloodstream and to evaluate the long-term response to IL-2.
  • Home treatment with interleukin-2 - Participants may receive future IL-2 treatment cycles at home. Home treatment involves less frequent data and safety monitoring and no medical evaluations at the Clinical Center except at the beginning of each cycle.

Condition Intervention Phase
Acquired Immunodeficiency Syndrome
HIV Infection
Drug: Interleukin-2
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Primary Purpose: Treatment
Official Title: A Phase I/II Pilot Study of the Safety of the Adoptive Transfer of Syngeneic Gene-Modified Cytotoxic T Lymphocytes in HIV Infected Identical Twins

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 100
Study Start Date: September 1994
Estimated Study Completion Date: June 2002
Detailed Description:

Open-label, comparative, sequentially randomized treatment with genetically unmodified or modified ex vivo-expanded T-lymphocytes in patients with HIV infection who possess a seronegative syngeneic twin. Genetic modification consists of introduction of a gene for HLA-unrestricted "universal" receptors specific for the gp120 HIV envelope protein. Treatment is divided into Periods I and II.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

An identical twin pair, one of whom is seropositive for HIV, the other twin seronegative, by standard ELISA, PCR, and Western blot testing.

Patients whose CD4+ count is less than 500/mm(3) at entry must have been on FDA-approved or expanded-access antiretroviral agent(s) for at least 2 months.

Patients with Kaposi's sarcoma 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.

Anticipated survival greater than 6 months and Karnofsky Performance Status greater than or equal to 60%.

Males or females 18 years of age or older. Every effort will be made to include both genders.

Free from serious psychological or emotional illness and able to provide written informed consent.

EXCLUSION CRITERIA - RECIPIENT:

Lymphoma.

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 positive sero-status and the risk of transmission of HIV 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.

Pregnancy at entry or unwillingness to practice barrier birth control or abstinence during the study.

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001409

Locations
United States, Maryland
National Institute of Allergy and Infectious Diseases (NIAID)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00001409     History of Changes
Other Study ID Numbers: 940206, 94-I-0206
Study First Received: November 3, 1999
Last Updated: March 3, 2008
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
AIDS
Gene Therapy
T Cell Universal Receptor
Ex Vivo Activation

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Interleukin-2
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 16, 2014