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Evaluation of the Safety and Tolerance of Immunotherapy With Autologous, Ex-Vivo Expanded, HIV-Specific Cytotoxic T-Cells in HIV-Infected Patients With CD4+ Counts Between 100-400/mm3

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Lymphocytes, Activated
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring T-Lymphocytes, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Immunotherapy, Adoptive, Transplantation, Autologous

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria Concurrent Medication: Allowed: Approved antiretroviral therapy and/or prophylactic PCP therapy, provided there was no change in such therapy in the 4 weeks prior to study entry. Other approved treatments for HIV-related diseases that are not known to affect cellular immune response. G-CSF. Erythropoietin. Supportive care for acute therapy-related toxicity. Patients must have: HIV infection. CD4 count 100 - 400 cells/mm3. No current or previously documented AIDS-related opportunistic infection, malignancy, or encephalopathy other than mild Kaposi's sarcoma. FEV1 > 70 percent, DLCO > 50 percent predicted for height and age (initial infusion only). T cell lines with specific cytotoxicity against HIV-1. Exclusion Criteria Co-existing Condition: Patients with the following symptoms or conditions are excluded: Significant autoimmune disease. Non-AIDS-associated malignancy. Symptoms of cardiac disease. Dyspnea on significant exertion. Acute infiltrates on chest radiographs. Patients with the following prior conditions are excluded: History of significant arrhythmia, infarction, or heart failure. History of a major psychiatric illness. Prior Medication: Excluded within 4 weeks prior to study entry: Systemic immunosuppressive therapy (i.e., steroids, cyclosporine, chemotherapy, or alpha-interferon). Therapy for acute infection, AIDS-related opportunistic infection, or malignancy. Experimental AIDS therapy. Prior Treatment: Excluded: Potentially immunosuppressive local therapy or radiation therapy for Kaposi's sarcoma within 4 weeks prior to study entry. Current substance abuse.

Sites / Locations

  • New England Med Ctr / Tufts Univ

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 27, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00000756
Brief Title
Evaluation of the Safety and Tolerance of Immunotherapy With Autologous, Ex-Vivo Expanded, HIV-Specific Cytotoxic T-Cells in HIV-Infected Patients With CD4+ Counts Between 100-400/mm3
Official Title
Evaluation of the Safety and Tolerance of Immunotherapy With Autologous, Ex-Vivo Expanded, HIV-Specific Cytotoxic T-Cells in HIV-Infected Patients With CD4+ Counts Between 100-400/mm3
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
June 2002 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

5. Study Description

Brief Summary
To determine the safety, tolerance, and feasibility of adoptive immunotherapy with autologous cytotoxic T-lymphocytes (CTLs) in HIV-infected patients with CD4 counts between 100 and 400; to evaluate the immunologic, virologic, and clinical changes for up to 24 weeks following infusion of study therapy. Freshly isolated peripheral blood lymphocytes from HIV-1-seropositive individuals frequently lyse autologous HIV-1-expressing cells or autologous cells infected with vaccinia vectors encoding HIV-1-specific proteins. Administration of these cytotoxic T lymphocytes (CTLs) may help prevent HIV disease progression.
Detailed Description
Freshly isolated peripheral blood lymphocytes from HIV-1-seropositive individuals frequently lyse autologous HIV-1-expressing cells or autologous cells infected with vaccinia vectors encoding HIV-1-specific proteins. Administration of these cytotoxic T lymphocytes (CTLs) may help prevent HIV disease progression. AMENDED 03/28/94: Patients are not accrued at the 25 billion CTL dose. Instead, a third cohort receives three infusions of 1 billion CTL 5-8 weeks apart. AMENDED 02/14/94: Patients infused with 1 or 5 billion CTL will be reinfused with 1 billion CTL 6-12 months later, and then followed for up to 12 weeks after the reinfusion. ORIGINAL DESIGN: Fifteen patients whose cells show an HIV-specific cytotoxic T lymphocyte (CTL) response are infused with autologous, ex-vivo expanded CTLs at a dose of 1, 5, or 25 billion cells (five patients per dose level). If one to three patients at a given dose develop acute toxicity, an additional three patients will be entered at that dose. If four patients at any given dose develop acute toxicity, the next lower dose will be designated as the MTD (if four patients develop acute toxicity in the first cohort, the study will be terminated). Patients are evaluated during infusion and at 1, 2, 4, 8, and 24 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
T-Lymphocytes, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Immunotherapy, Adoptive, Transplantation, Autologous

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Masking
None (Open Label)
Enrollment
15 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Lymphocytes, Activated

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Concurrent Medication: Allowed: Approved antiretroviral therapy and/or prophylactic PCP therapy, provided there was no change in such therapy in the 4 weeks prior to study entry. Other approved treatments for HIV-related diseases that are not known to affect cellular immune response. G-CSF. Erythropoietin. Supportive care for acute therapy-related toxicity. Patients must have: HIV infection. CD4 count 100 - 400 cells/mm3. No current or previously documented AIDS-related opportunistic infection, malignancy, or encephalopathy other than mild Kaposi's sarcoma. FEV1 > 70 percent, DLCO > 50 percent predicted for height and age (initial infusion only). T cell lines with specific cytotoxicity against HIV-1. Exclusion Criteria Co-existing Condition: Patients with the following symptoms or conditions are excluded: Significant autoimmune disease. Non-AIDS-associated malignancy. Symptoms of cardiac disease. Dyspnea on significant exertion. Acute infiltrates on chest radiographs. Patients with the following prior conditions are excluded: History of significant arrhythmia, infarction, or heart failure. History of a major psychiatric illness. Prior Medication: Excluded within 4 weeks prior to study entry: Systemic immunosuppressive therapy (i.e., steroids, cyclosporine, chemotherapy, or alpha-interferon). Therapy for acute infection, AIDS-related opportunistic infection, or malignancy. Experimental AIDS therapy. Prior Treatment: Excluded: Potentially immunosuppressive local therapy or radiation therapy for Kaposi's sarcoma within 4 weeks prior to study entry. Current substance abuse.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
J Lieberman
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
H Standiford
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
D Stein
Official's Role
Study Chair
Facility Information:
Facility Name
New England Med Ctr / Tufts Univ
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
9310470
Citation
Lieberman J, Skolnik PR, Parkerson GR 3rd, Fabry JA, Landry B, Bethel J, Kagan J. Safety of autologous, ex vivo-expanded human immunodeficiency virus (HIV)-specific cytotoxic T-lymphocyte infusion in HIV-infected patients. Blood. 1997 Sep 15;90(6):2196-206.
Results Reference
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Evaluation of the Safety and Tolerance of Immunotherapy With Autologous, Ex-Vivo Expanded, HIV-Specific Cytotoxic T-Cells in HIV-Infected Patients With CD4+ Counts Between 100-400/mm3

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