Dose Escalation Study of Cyclophosphamide in HIV-Infected Subjects on HAART Receiving SB-728-T
- Conditions
- HIV
- Interventions
- Genetic: SB-728-T
- Registration Number
- NCT01543152
- Lead Sponsor
- Sangamo Therapeutics
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 26
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 1 - IV cyclophosphamide 200 mg SB-728-T - Cohort 2 - IV cyclophosphamide 0.5 g/m2 SB-728-T - Cohort 3 - IV cyclophosphamide 1.0 g/m2 SB-728-T - Cohort 4 - IV cyclophosphamide 2.0 g/m2 SB-728-T - Cohort 5 - IV cyclophosphamide 1.5 g/m2 SB-728-T -
- Primary Outcome Measures
Name Time Method Treatment-emergent Adverse Events 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 Outcome Measures
Name Time Method 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 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)
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 SB-728-T on plasma HIV-1 RNA levels following HAART interruption. The unit is log copies/mL, except for the Cohort 1, the unit is " copies/mL".
Cohort 1 mean and SD are 0. All 3 subjects had NO HIV-1 RNA DETECTED.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 Effect of repeat doses of SB-728-T on engraftment following cyclophosphamide conditioning as measured by CCR5 Modified CD4 Cells in blood at Month 12.
Trial Locations
- Locations (11)
UCLA Care Center
🇺🇸Los Angeles, California, United States
Quest Clinical Research
🇺🇸San Francisco, California, United States
Circle CARE Center, LLC
🇺🇸Norwalk, Connecticut, United States
Orlando Immunology Center
🇺🇸Orlando, Florida, United States
Central West Clinical Research, Inc.
🇺🇸Saint Louis, Missouri, United States
Ricky K Hsu, MD, PC
🇺🇸New York, New York, United States
Southwest CARE Center
🇺🇸Santa Fe, New Mexico, United States
Central Texas Clinical Research
🇺🇸Austin, Texas, United States
North Texas Infectious Diseases Consultants
🇺🇸Dallas, Texas, United States
Gordon Crofoot, MD, PA
🇺🇸Houston, Texas, United States
Clinical Research Puerto Rico
🇵🇷San Juan, Puerto Rico