IMMUNE BASED THERAPIES
Phase 1 Dose Escalation Study of Autologous T-cells Genetically Modified at the CCR5 Gene by Zinc Finger Nucleases in HIV-Infected Patients
The purpose of this research study is to find out whether "zinc finger" modified CD4+ T-cells are safe to give to humans and find how "zinc finger" modified T-cell affects HIV. Five different cohorts with different patient characteristics are being recruited
Dose Escalation Study of Cyclophosphamide in HIV-Infected Subjects on HAART Receiving Sangamo's SB-728-T
The purpose of the study is to evaluate the safety, tolerability and effect on HIV viral load, of escalating doses of cyclophosphamide administered 1 day prior to SB-728-T infusion. It is hoped that cyclophosphamide could improve engraftment of modified T cells.
High-Dose Chemotherapy With Transplantation of Gene-Modified Stem Cells for High-Risk AIDS-Related Lymphoma
Patient stem cells will be mobilized with induction chemotherapy (R)-ICE and G-CSF. If sufficient cells can be mobilized, patients will be treated with high-dose chemotherapy and a transplant of autologous CD34+ cells transduced with an antiviral vector (M87o). If autologous CD34+ yield is insufficient, allogeneic gene-modified cells will be given, if a compatible donor is available. To minimize risk of transplant failure, a second unmodified CD34+ cell transplant will be given one week after the first transplant.
Genetically Engineered Lymphocyte Therapy After Peripheral Blood Stem Cell Transplant in Treating Patients With High-Risk, Intermediate-Grade, B-cell Non-Hodgkin Lymphoma
This phase I/II trial studies the side effects and best dose of genetically engineered lymphocyte therapy and to see how well it works after peripheral blood stem cell transplant (PBSCT) in treating patients with high-risk, intermediate-grade, B-cell non-Hodgkin lymphoma (NHL). Genetically engineered lymphocyte therapy may stimulate the immune system in different ways and stop cancer cells from growing. Giving rituximab together with chemotherapy before a PBSCT stops the growth of cancer cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as filgrastim (G-CSF), or plerixafor helps stem cells move from the bone marrow to the blood so they can be collected and stored. More chemotherapy or radiation therapy is given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. Giving genetically engineered lymphocyte therapy after PBSCT may be an effective treatment for NHL
ACE Inhibitors to Decrease Lymphoid Fibrosis in Antiretroviral-Treated, HIV-infected Patients: A Pilot Study
The investigators propose a proof-of-concept, pathogenesis-oriented, randomized, placebo-controlled pilot study to assess whether the addition of an angiotensin converting enzyme (ACE) inhibitor to standard Highly Active Antiretroviral Therapy (HAART) reverses lymphoid fibrosis, and whether this leads to more effective HIV-specific host immune responses and an accelerated clearance of the latent reservoir
Safety and Efficacy Study of AGS-004 During Analytical Treatment Interruption
The purpose of this study is to determine the safety and effectiveness of AGS-004, an immune therapy, for HIV-infected individuals. Safety and effectiveness will be tested while the individuals are both taking antiretroviral therapy (ART) medication and interrupting ART medication.
THERAPEUTIC HIV VACCINES
Screening Protocol for HIV Vaccine Studies
Individuals who are identified through this screening protocol as possible candidates for an HIV vaccine trial will be provided additional information about study options.
A Phase Il of a Therapeutic, Recombinant, Biologically Active HIV-1 Tat Protein Vaccine in HIV-Infected, Anti-Tat Negative, ARV-Treated Adult Volunteers (ISS T-003)
Tat is a key HIV regulatory protein produced very early after infection, prior to virus integration, and necessary for viral gene expression, cell-to-cell virus transmission and disease progression. Previous studies in natural HIV infection, indicated that the presence of a Tat-specific immune response correlates with a lower incidence and reduced risk of progression to AIDS as compared to anti-Tat negative individuals suggesting that an immune response to Tat may exert a protective role and control the progression to AIDS in vivo. Moreover Tat is conserved in its immunogenic regions (both B and T cell) among all subtypes. subtypes. Recent data, in fact, indicate an effective cross-clade recognition of clade B strain-derived (BH-10) Tat protein from the HTLV-IIIB lab-adapted virus strain (Buttò, 2003), which was isolated about 20 years ago (Ratner, 1985), by sera from individuals infected with viruses circulating at the present in Italy and in Africa, thus reflecting the high degree of conservation of the corresponding Tat regions and providing strong formal evidence that a Tat-based vaccine may indeed be used in the different geographic areas of the world, since it is capable of inducing a broad immune response against different virus clades. Based on this rationale and on the positive results of preclinical (Cafaro, Nat Med 1999) and phase I preventive and therapeutic clinical trials with Tat protein (ISS P-001 and ISS T-001, respectively) (Ensoli AIDS 2008, Vaccine 2009; LongoVaccine 2009; Bellino RRCT, 2009) a phase II therapeutic, open label, clinical study with Tat protein (ISS T-002, ClinicalTrials.gov NCT00751595) was sponsored by ISS and activated in 11 clinical sites in Italy in HIV-infected HAART-treated subjects.In this study, subjects are randomized into two arms to receive 3 or 5 vaccinations monthly; each arm is composed of two treatment groups, receiving 7, 5 or 30 µg of Tat, respectively. Preliminary results obtained from 87 subjects enrolled in the phase II trial ISST-002 ongoing in Italy, indicate that Tat vaccination is safe, immunogenic and capable of reducing the immune dysregulation which persists despite HAART in treated individuals, opening new avenues for a most effective treatment of HIV/AIDS (Ensoli et al,PLoS ONE 2010).
Immunomodulating Therapy and Improved Vaccination Responses by Cox-2 Inhibitor in HIV-infected Patients (OUSCOX2)Chronic immune activation is a central feature of HIV-infection, and the degree of activated T-cells is a better predictor of disease progression and mortality than plasma viral load. The study hypothesis is that the anti-inflammatory substance etoricoxib will dampen chronic immune activation and improve the effect of T-cell dependent vaccines in HIV-1 infected patients.