Clinical trial NCT01543152: Dose Escalation Study of Cyclophosphamide in HIV-Infected Subjects on HAART Receiving SB-728-T
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: HIV
Keywords: HIV
autologous cell therapy
cyclophosphamide
Lead sponsor: Sangamo Therapeutics
Sponsor class: INDUSTRY
First posted: 2012-03-02
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Treatment-emergent Adverse Events
timeFrame: 28 days after the SB-728-T infusion of the last subject in each Cohort and up to 12 months
Secondary outcomes:
measure: Effect of Escalating Doses of Cyclophosphamide on SB-728-T Engraftment as Measured by CCR5 Modified CD4 Cells in Blood.
timeFrame: Up to 12 months after the last SB-728-T infusion
measure: Effect of SB-728-T on Plasma HIV-1 RNA Levels Following HAART Interruption
timeFrame: Up to 12 months after the last SB-728-T infusion
measure: 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)
timeFrame: Up to 12 months after the last SB-728-T infusion
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Care Center
state: California
city: San Francisco
country: United States
facility: Quest Clinical Research
state: California
city: Norwalk
country: United States
facility: Circle CARE Center, LLC
state: Connecticut
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Saint Louis
country: United States
facility: Central West Clinical Research, Inc.
state: Missouri
city: Santa Fe
country: United States
facility: Southwest CARE Center
state: New Mexico
city: New York
country: United States
facility: Ricky K Hsu, MD, PC
state: New York
city: Austin
country: United States
facility: Central Texas Clinical Research
state: Texas
city: Dallas
country: United States
facility: North Texas Infectious Diseases Consultants
state: Texas
city: Houston
country: United States
facility: Gordon Crofoot, MD, PA
state: Texas
city: San Juan
country: Puerto Rico
facility: Clinical Research Puerto Rico
Study officials:
References: