A Phase I Study of Autologous, Activated CD8(+) Lymphocytes Expanded In Vitro and Infused With or Without Recombinant Interleukin-2 to Patients With AIDS or Severe ARC

• Status: Completed
• Trial end date: 1993-04-01
• Target enrollment: 0
• Participant gender: All

Summary

1) To determine whether it is possible to remove and culture (increase in number and activate) in the laboratory, CD8(+) lymphocytes (white blood cells) from HIV-infected patients receiving zidovudine (AZT); 2) To determine the toxicity of returning to the patients intravenously the expanded and activated autologous cells (given to the patient from whom they were taken), with and without giving the patients recombinant interleukin-2 ( aldesleukin; IL-2 ) at the same time; 3) To radiolabel (mark) the CD8(+) lymphocytes with Indium 111, and then scan the patients to determine the distribution of the CD8(+) lymphocytes in those who are and are not given IL-2 infusions; 4) To determine the toxicity of IL-2 given at the same time with autologous CD8(+) lymphocytes; 5) To measure changes in the immunology of the subjects following these treatments.

CD8(+) cells are suppressor/killer lymphocyte cells that act to limit replication of viruses. It is hoped that the reinfusion of activated autologous CD8(+) cells into patients with AIDS will help to control opportunistic infections such as cytomegalovirus and toxoplasmosis (two of the leading causes of sickness and death in AIDS patients). This treatment may also stop the HIV virus from replicating (reproducing itself) in the AIDS patient. Further activation of these cells, once infused, may be necessary. It is hoped that IL-2 will stimulate the patient's immune system against the AIDS virus along with the activated CD8(+) cells. Thus, IL-2 will be given, and its effects studied.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborator: Applied Immunesciences
• Treatments: Aldesleukin; Interleukin-2; Zidovudine

Criteria

Inclusion Criteria

Concurrent Medication:

Required:

• Zidovudine (AZT) during treatment and for 20 weeks after the last infusion unless medically contraindicated.

• Allowed:

• Aerosolized pentamidine for Pneumocystis carinii pneumonia (PCP) prophylaxis.

• Oral antibiotics for PCP prophylaxis if hematologically stable on that regimen for at least 30 days prior to study entry.

Patients must have the following:

• Positive HIV antibody test by federally licensed ELISA.

• Positive HIV culture or plasma p24 antigen.

• CDC Group IV severe AIDS-related complex (ARC) or AIDS.

• Must have been on zidovudine (AZT) at least 6 weeks prior to infusion and agree to continue this medication during the study and for 20 weeks after the last infusion unless medically contraindicated.

• Allowed:

• Kaposi's sarcoma.

Exclusion Criteria

Co-existing Condition:

AMENDED:

• Pulmonary diseases that require treatment.

• AMENDED:

• Significant central nervous system disease including AIDS dementia, psychiatric disabilities, or seizure disorders.

• AMENDED:

• Symptomatic HIV CNS infections or symptoms compatible with HIV encephalopathy.

• Original design:

• Patients with the following conditions or symptoms are excluded:

• Active bacterial or opportunistic infection that requires treatment.

• Neoplasms not specifically allowed, basal cell carcinoma of the skin, or in-situ carcinoma of the cervix.

• Clinically significant cardiac (= or > class II, New York Heart Association) or peripheral vascular disease that requires treatment.

• Hemorrhagic diathesis including hemophilia or active bleeding disorder.

Concurrent Medication:

Excluded:

• Antineoplastic therapy.

• Medication required for treatment of active cardiac disease.

• Cardiac glycosides.

• Antiarrhythmics.

• Antianginal agents.

• Anticoagulants.

• Thrombolytic agents.

• Vasodilators.

• Excluded within 30 days of study entry:

• Antiretroviral agents not specifically allowed.

• Corticosteroids.

• Acyclovir.

• Excluded within 60 days of study entry:

• Biological response modifiers.

Patients with the following are excluded:

• Unable to give properly informed consent by reason of impaired mentation.

• Diseases and conditions specified elsewhere in the protocol.

Required:

• Zidovudine (AZT) for at least 6 weeks prior to infusion.

Risk Behavior: Excluded:

• Active substance abuse.