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
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
HIV Infections |
Drug: Zidovudine Drug: Aldesleukin |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Masking: Open Label Primary Purpose: Treatment |
| Official Title: | 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 |
| Estimated Enrollment: | 6 |
| Study Completion Date: | April 1993 |
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.
AMENDED: 09/28/90 The CD8 lymphocytes are grown in vitro for 21 days before infusion. Leukapheresis and infusion continue every 21 days for 3 infusions with the last infusion during week 16. During weeks 13 and 16, indium 111 radio labelled cells are injected to permit determination of the distribution and pharmacokinetics of the infused cells. At week 16, IL-2 is administered concurrently with Indium 111 labelled cells and the CD8+ lymphocytes - delivered by continuous infusion over 5 days following cell infusion. Patients are followed at the clinic 1 week prior to scheduled infusions, during infusion weeks and then every 2 weeks to week 21 and at week 27. Original design: Patients undergo leukapheresis every 2 weeks for a total of 6 times during the initial phase of the study. During this procedure, a catheter is placed in an arm vein, and the blood flows through a machine which separates the lymphocytes from the other blood components. The blood is then returned to the patient's body through the catheter. Less than 10 percent of the lymphocytes in the blood are removed during the process. The CD8(+) cells taken from the patient are cultured in the laboratory until they increase 10- to 1000-fold. These cells are then infused back into the patient from whom they were taken. The first two patients are admitted for 24 hours at the time of each infusion. In the absence of severe side effects, the subsequent four patients are infused at the clinic. Patients are admitted for 5 days for continuous infusion of IL-2 in week 13.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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.
Contacts and Locations| United States, Pennsylvania | |
| Univ of Pittsburgh Med School | |
| Pittsburgh, Pennsylvania, United States | |
| Study Chair: | M Ho | |
| Study Chair: | R Herberman | |
| Study Chair: | J Armstrong |
More Information
Additional Information:
Publications:
| Responsible Party: | National Institute of Allergy and Infectious Diseases (NIAID) |
| ClinicalTrials.gov Identifier: | NCT00000680 History of Changes |
| Other Study ID Numbers: | ACTG 080, 11055 |
| Study First Received: | November 2, 1999 |
| Last Updated: | May 22, 2012 |
| Health Authority: | United States: Federal Government |
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
|
T-Lymphocytes, Suppressor-Effector Indium Radioisotopes Leukapheresis Interleukin-2 |
Acquired Immunodeficiency Syndrome AIDS-Related Complex Zidovudine Immunization, Passive |
Additional relevant MeSH terms:
|
HIV Infections Acquired Immunodeficiency Syndrome Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Slow Virus Diseases Aldesleukin Interleukin-2 Zidovudine 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 Antimetabolites Molecular Mechanisms of Pharmacological Action Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Anti-Retroviral Agents Antiviral Agents |
ClinicalTrials.gov processed this record on May 23, 2013