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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00000680

Collaborator

Applied Immunesciences (Industry)

Enrollment

Location

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: Zidovudine Drug: Aldesleukin	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Masking:

None (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

Actual Study Completion Date :

Apr 1, 1993

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.