HIV Infection Clinical Trial
Official title:
A Study of the Safety and Survival of the Adoptive Transfer of Genetically Marked Syngeneic Lymphocytes in HIV-Infected Identical Twins
This study will evaluate the safety of giving lymphocytes (white blood cells) containing a
new gene to HIV-infected individuals and will determine how long the cells survive in the
bloodstream. Although the genetically altered cells will not directly benefit participants,
knowledge about the safety, side effects and survival of these gene-marked cells in
HIV-infected patients may lead to new treatment strategies.
Identical twin pairs 18 years of age and older-one infected with HIV, the other
non-infected-may be eligible for this study. Candidates will be screened with a medical
history, physical examination and blood tests.
All participants will have a tetanus booster shot. Non-infected twins will undergo a
procedure called apheresis to collect white blood cells. For this procedure, whole blood is
collected through a needle in an arm vein, similar to donating blood. The blood is separated
it into its components by centrifugation (spinning), the white cells are removed, and the
rest of the blood is returned to the body, either through the same needle or through another
needle in the other arm. The harvested white cells will be grown in culture for
approximately 10 days to 2 weeks to increase their numbers up to 1000-fold. A gene called
NeoR, which is derived from bacteria, will be inserted into the cells, and these gene-marked
cells will be infused into the HIV-infected twin.
HIV-infected twins will be admitted to the NIH Clinical Center for the first cell infusion.
The gene-marked cells will be infused over a 60-minute period through a plastic tube
(catheter) placed in an arm vein, or, if a suitable arm vein cannot be found, through a
special catheter placed into a large vein in the neck or chest. Vital signs (temperature,
pulse, blood pressure and breathing rate), blood oxygen concentration, and urine output will
be monitored regularly for 24 hours. Blood samples will be collected before and after the
infusion to monitor for gene-marked cells. Patients will be discharged the next day. They
will return to NIH daily the first week (from Monday through Thursday) to monitor for CD4
cell counts, plasma viral burden, p24 antigen levels, HIV levels and the presence of the
NeoR gene, and then weekly for the next 5 weeks for these tests and others to monitor blood
and urine chemistry, blood counts and immune function markers.
If the NeoR gene cannot be detected after the first cell infusion, the entire procedure
(donor apheresis, gene marking and infusion of cells) will be repeated twice-about once
every 6 weeks. If the first infusion was uncomplicated, the second and third infusions may
be done on an outpatient basis, with monitoring for 6 hours rather than 24. Six weeks after
the third infusion, tests will be scheduled monthly for 6 months and then yearly for
long-term follow-up.
In addition to the above procedures, patients with a baseline CD4 lymphocyte count less than
100 cells per cubic millimeter of blood will be asked to undergo apheresis periodically to
obtain the most accurate results for determining how long the NeoR gene persists in the
blood. The procedure will be done weekly for the first 6 weeks after each infusion of cells,
then at week 8, and then every 4 weeks until the gene can no longer be detected in the
lymphocytes. The schedule may change, but will not require more frequent apheresis.
Status | Completed |
Enrollment | 24 |
Est. completion date | March 2002 |
Est. primary completion date | |
Accepts healthy volunteers | No |
Gender | Both |
Age group | N/A and older |
Eligibility |
An identical twin pair, one of whom is seropositive for HIV, the other twin seronegative,
by standard ELISA and Western blot testing. Patients with Kaposi's sarcoma are eligible for this study, but must not have received any systemic therapy for KS within 4 weeks prior to entry. The diagnosis of KS must have been confirmed by biopsy. Patients must be free from serious psychological or emotional illness and able to provide written informed consent. Anticipated survival greater than 3 months. 18 years of age or older. Treatment with FDA-approved and/or expanded access antiretroviral agent(s) for patients with baseline CD4 counts below 500 cells/mm3. Patients with baseline CD4 counts above 500 cells/mm3 are eligible to receive cell therapy on this protocol, but must be treated with antiretroviral therapy if evidence of significant and persistent viral activation occurs in association with a cell infusion (a 50 percent or greater increase above baseline in any virologic parameter for at least 2 consecutive weeks). No patients with lymphoma. Willing to comply with current NIH Clinical Center guidelines concerning appropriate notification of all current sexual partners of an individual regarding his or her HIV positive sero-status and the risk of transmission of HIV infection. No recent history of substance abuse unless evidence is provided of an ongoing therapeutic intervention (i.e., medical therapy or counseling) to control such abuse. No pregnancy. |
N/A
Country | Name | City | State |
---|---|---|---|
United States | National Institute of Allergy and Infectious Diseases (NIAID) | Bethesda | Maryland |
Lead Sponsor | Collaborator |
---|---|
National Institute of Allergy and Infectious Diseases (NIAID) |
United States,
Lane HC, Masur H, Longo DL, Klein HG, Rook AH, Quinnan GV Jr, Steis RG, Macher A, Whalen G, Edgar LC, et al. Partial immune reconstitution in a patient with the acquired immunodeficiency syndrome. N Engl J Med. 1984 Oct 25;311(17):1099-103. — View Citation
Lane HC, Zunich KM, Wilson W, Cefali F, Easter M, Kovacs JA, Masur H, Leitman SF, Klein HG, Steis RG, et al. Syngeneic bone marrow transplantation and adoptive transfer of peripheral blood lymphocytes combined with zidovudine in human immunodeficiency virus (HIV) infection. Ann Intern Med. 1990 Oct 1;113(7):512-9. — View Citation
Rosenberg SA, Aebersold P, Cornetta K, Kasid A, Morgan RA, Moen R, Karson EM, Lotze MT, Yang JC, Topalian SL, et al. Gene transfer into humans--immunotherapy of patients with advanced melanoma, using tumor-infiltrating lymphocytes modified by retroviral gene transduction. N Engl J Med. 1990 Aug 30;323(9):570-8. — View Citation
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