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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 21
- 主要终点
- Treatment-emergent Adverse Events
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
结局指标
主要结局
Treatment-emergent Adverse Events
时间窗: 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
次要结局
- 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)