A Phase I, Open-Label Study to Assess the Effect of Escalating Doses of Cyclophosphamide on the Engraftment of SB-728-T in Aviremic HIV-Infected Subjects on HAART
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- HIV
- Sponsor
- Sangamo Therapeutics
- Enrollment
- 26
- Locations
- 11
- Primary Endpoint
- Treatment-emergent Adverse Events
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
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.
Detailed Description
The objectives of the study are to augment HIV-specific T-cells and to reverse or decrease the progressive destruction of CD4+ T-cells that leads to clinical AIDS. Levels of engraftment vary from negligible to about 10% of the CD4+ T-cells in the vascular compartment. Preliminary analyses of HAART TI suggest that an anti-HIV effect may correlate with the level of SB-728-T engraftment. Concurrently, non-myeloablative lymphodepletion with cyclophosphamide has been demonstrated to enhance engraftment of adoptively transferred T-cells through a variety of mechanisms. The study is being undertaken to increase SB-728-T engraftment through the administration of low non-myeloablative doses of cyclophosphamide.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female, 18 years of age or older with documented HIV diagnosis within 10 years of screening.
- •Must be willing to comply with study-mandated evaluations; including discontinuation of current antiretroviral therapy during the treatment interruption.
- •Must have received at least 6 months of continuous HAART therapy and have had undetectable VLs for the preceding 3 months.
- •On stable antiretroviral medication (no changes to treatment within 4 weeks of screening.
- •CD4+ T-cell count ≥500 cells/µL.
- •Undetectable HIV-1 RNA obtained at screening.
- •ANC ≥2500/µL
- •Platelet count ≥200,000/µL
Exclusion Criteria
- •Acute or chronic hepatitis B or hepatitis C infection.
- •Active or recent (in prior 6 months) AIDS defining complication.
- •Any cancer or malignancy within the past 5 years, with the exception of successfully treated basal cell or squamous cell carcinoma of the skin or low grade (0 or 1) anal or cervical dysplasia.
- •Current diagnosis of NYHA grade 3 or 4 CHF, uncontrolled angina or arrhythmias.
- •History or any features on physical examination indicative of a bleeding diathesis.
- •Received HIV experimental vaccine within 6 months prior to screening, or any previous gene therapy using an integrating vector.
- •Use of chronic corticosteroids, hydroxyurea, or immunomodulating agents within 30 days prior to screening.
- •Use of Aspirin, dipyridamole, warfarin or any other medication that is likely to affect platelet function or other aspects of blood coagulation during the 2 week period prior to leukapheresis.
- •Currently participating in another clinical trial or participation in such a trial within 30 days prior to screening visit.
- •Subjects who are currently taking maraviroc or have received maraviroc within 6 months prior to screening.
Outcomes
Primary Outcomes
Treatment-emergent Adverse Events
Time Frame: 28 days after the SB-728-T infusion of the last subject in each Cohort and up to 12 months
Number of Participants with Treatment related Adverse Events in subjects who received any portion of the SB-728-T infusion
Secondary Outcomes
- Change From Baseline to Month 12 in CD4+ T-cell Counts in Peripheral Blood After Repeat Treatments With SB-728-T. (i.e. Month 12 Value - Baseline Value)(Up to 12 months after the last SB-728-T infusion)
- Effect of SB-728-T on Plasma HIV-1 RNA Levels Following HAART Interruption(Up to 12 months after the last SB-728-T infusion)
- Effect of Escalating Doses of Cyclophosphamide on SB-728-T Engraftment as Measured by CCR5 Modified CD4 Cells in Blood.(Up to 12 months after the last SB-728-T infusion)