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

April 26, 2021 updated by: Sangamo Therapeutics

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

26

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Puerto Rico
      • San Juan, Puerto Rico, 00909
        • Clinical Research Puerto Rico
  • United States
    • California
      • Los Angeles, California, United States, 90035
        • UCLA CARE Center
      • San Francisco, California, United States, 94115
        • Quest Clinical Research
    • Connecticut
      • Norwalk, Connecticut, United States, 06850
        • Circle CARE Center, LLC
    • Florida
      • Orlando, Florida, United States, 32803
        • Orlando Immunology Center
    • Missouri
      • Saint Louis, Missouri, United States, 63108
        • Central West Clinical Research, Inc.
    • New Mexico
      • Santa Fe, New Mexico, United States, 87505
        • Southwest CARE Center
    • New York
      • New York, New York, United States, 10011
        • Ricky K Hsu, MD, PC
    • Texas
      • Austin, Texas, United States, 78705
        • Central Texas Clinical Research
      • Dallas, Texas, United States, 75246
        • North Texas Infectious Diseases Consultants
      • Houston, Texas, United States, 77098
        • Gordon Crofoot, MD, PA

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1 - IV cyclophosphamide 200 mg
Genetic: SB-728-T
Infusion will be 5 to 30 billion ZFN modified CD4+ T cells 1 day following IV cyclophosphamide 200 mg
Other Names:
  • cyclophosphamide
Genetic: 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
Other Names:
  • cyclophosphamide
Genetic: 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
Other Names:
  • cyclophosphamide
Genetic: 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
Other Names:
  • cyclophosphamide
Genetic: 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
Other Names:
  • cyclophosphamide
Experimental: Cohort 2 - IV cyclophosphamide 0.5 g/m2
Genetic: SB-728-T
Infusion will be 5 to 30 billion ZFN modified CD4+ T cells 1 day following IV cyclophosphamide 200 mg
Other Names:
  • cyclophosphamide
Genetic: 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
Other Names:
  • cyclophosphamide
Genetic: 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
Other Names:
  • cyclophosphamide
Genetic: 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
Other Names:
  • cyclophosphamide
Genetic: 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
Other Names:
  • cyclophosphamide
Experimental: Cohort 3 - IV cyclophosphamide 1.0 g/m2
Genetic: SB-728-T
Infusion will be 5 to 30 billion ZFN modified CD4+ T cells 1 day following IV cyclophosphamide 200 mg
Other Names:
  • cyclophosphamide
Genetic: 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
Other Names:
  • cyclophosphamide
Genetic: 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
Other Names:
  • cyclophosphamide
Genetic: 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
Other Names:
  • cyclophosphamide
Genetic: 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
Other Names:
  • cyclophosphamide
Experimental: Cohort 4 - IV cyclophosphamide 2.0 g/m2
Genetic: SB-728-T
Infusion will be 5 to 30 billion ZFN modified CD4+ T cells 1 day following IV cyclophosphamide 200 mg
Other Names:
  • cyclophosphamide
Genetic: 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
Other Names:
  • cyclophosphamide
Genetic: 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
Other Names:
  • cyclophosphamide
Genetic: 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
Other Names:
  • cyclophosphamide
Genetic: 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
Other Names:
  • cyclophosphamide
Experimental: Cohort 5 - IV cyclophosphamide 1.5 g/m2
Genetic: SB-728-T
Infusion will be 5 to 30 billion ZFN modified CD4+ T cells 1 day following IV cyclophosphamide 200 mg
Other Names:
  • cyclophosphamide
Genetic: 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
Other Names:
  • cyclophosphamide
Genetic: 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
Other Names:
  • cyclophosphamide
Genetic: 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
Other Names:
  • cyclophosphamide
Genetic: 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
Other Names:
  • cyclophosphamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
28 days after the SB-728-T infusion of the last subject in each Cohort and up to 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effect of Escalating Doses of Cyclophosphamide on SB-728-T Engraftment as Measured by CCR5 Modified CD4 Cells in Blood.
Time Frame: 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.
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
Time Frame: 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.
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)
Time Frame: 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)
Up to 12 months after the last SB-728-T infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sangamo Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2011

Primary Completion (Actual)

July 7, 2017

Study Completion (Actual)

July 7, 2017

Study Registration Dates

First Submitted

March 1, 2012

First Submitted That Met QC Criteria

March 1, 2012

First Posted (Estimate)

March 2, 2012

Study Record Updates

Last Update Posted (Actual)

May 24, 2021

Last Update Submitted That Met QC Criteria

April 26, 2021

Last Verified

October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SB-728-1101

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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