Dose Escalation Study of Cyclophosphamide in HIV-Infected Subjects on HAART Receiving SB-728-T

HIV Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01543152
• Other study ID #: SB-728-1101
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: December 2011
• Est. completion date: July 7, 2017

Study information

• Verified date: October 2017
• Source: Sangamo Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: July 7, 2017
• Est. primary completion date: July 7, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV

Intervention

Genetic:
• SB-728-T
Infusion will be 5 to 30 billion ZFN modified CD4+ T cells 1 day following IV cyclophosphamide 200 mg
• SB-728-T
Infusion will be 5 to 30 billion ZFN modified CD4+ T cells up to 3 days following IV cyclophosphamide 0.5 g/m2
• SB-728-T
Infusion will be 5 to 30 billion ZFN modified CD4+ T cells up to 3 days following IV cyclophosphamide 1.0 g/m2
• SB-728-T
Infusion will be 5 to 30 billion ZFN modified CD4+ T cells up to 3 days following IV cyclophosphamide 2.0 g/m2
• SB-728-T
Infusion will be 5 to 30 billion ZFN modified CD4+ T cells up to 3 days following IV cyclophosphamide 1.5 g/m2

Locations

Country	Name	City	State
Puerto Rico	Clinical Research Puerto Rico	San Juan
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	UCLA Care Center	Los Angeles	California
United States	Ricky K Hsu, MD, PC	New York	New York
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	Quest Clinical Research	San Francisco	California
United States	Southwest CARE Center	Santa Fe	New Mexico

Sponsors (1)

Lead Sponsor	Collaborator
Sangamo Therapeutics

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment-emergent Adverse Events	Number of Participants with Treatment related Adverse Events in subjects who received any portion of the SB-728-T infusion	28 days after the SB-728-T infusion of the last subject in each Cohort and up to 12 months
Secondary	Effect of Escalating Doses of Cyclophosphamide on SB-728-T Engraftment as Measured by CCR5 Modified CD4 Cells in Blood.	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.	Up to 12 months after the last SB-728-T infusion
Secondary	Effect of SB-728-T on Plasma HIV-1 RNA Levels Following HAART Interruption	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.	Up to 12 months after the last SB-728-T infusion
Secondary	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)	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