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

This study has been completed.
Sponsor:
Collaborator:
Applied Immunesciences
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000680
First received: November 2, 1999
Last updated: May 22, 2012
Last verified: May 2012
  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

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 6
Study Completion Date: April 1993
Detailed Description:

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
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000680

Locations
United States, Pennsylvania
Univ of Pittsburgh Med School
Pittsburgh, Pennsylvania, United States
Sponsors and Collaborators
Applied Immunesciences
Investigators
Study Chair: M Ho
Study Chair: R Herberman
Study Chair: J Armstrong
  More Information

Additional Information:
Publications:
Ho M, et al. Phase I study of in vitro purified and expanded autologous CD8(+) lymphocytes infused into patients with advanced ARC or AIDS (ACTG 080). Int Conf AIDS. 1991 Jun 16-21;7(2):77 (abstract no THB83)
Armstrong JA, Ho M, Herberman R, Elder E, Ferbas J, McMahon D, Gupta P, Rinaldo C, Whiteside T. A phase I study of autologous, activated CD8(+) lymphocytes expanded in vitro infused into patients with advanced ARC or AIDS (ACTG 080). Int Conf AIDS. 1990 Jun 20-23;6(3):208 (abstract no SB491)

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 April 17, 2014