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CompletedNCT01543152Updated May 24, 2021Results posted

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

A Phase 1/2 interventional study of SB-728-T and SB-728-T in HIV, sponsored by Sangamo Therapeutics. Completed at 11 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-05-24.

Sponsored by Sangamo Therapeutics · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
26
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • HIV

Keywords

  • HIV
  • autologous cell therapy
  • cyclophosphamide
03

In context

Lead sponsor

Sangamo Therapeutics is the lead sponsor of 27 studies on the registry; 1 is open to participants now.

Of its 6 completed or terminated interventional studies of FDA-regulated products, 4 (67%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
26 participants (actual)

Study arms

  • Experimental
    Cohort 1 - IV cyclophosphamide 200 mg

    Genetic: SB-728-T

  • Experimental
    Cohort 2 - IV cyclophosphamide 0.5 g/m2

    Genetic: SB-728-T

  • Experimental
    Cohort 3 - IV cyclophosphamide 1.0 g/m2

    Genetic: SB-728-T

  • Experimental
    Cohort 4 - IV cyclophosphamide 2.0 g/m2

    Genetic: SB-728-T

  • Experimental
    Cohort 5 - IV cyclophosphamide 1.5 g/m2

    Genetic: SB-728-T

Interventions

  • GeneticSB-728-T

    Infusion will be 5 to 30 billion ZFN modified CD4+ T cells 1 day following IV cyclophosphamide 200 mg

    Also known as: cyclophosphamide

  • GeneticSB-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

    Also known as: cyclophosphamide

  • GeneticSB-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

    Also known as: cyclophosphamide

  • GeneticSB-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

    Also known as: cyclophosphamide

  • GeneticSB-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

    Also known as: cyclophosphamide

06

What researchers measure

Primary outcomes

  1. Treatment-emergent Adverse Events

    Number of Participants with Treatment related Adverse Events in subjects who received any portion of the SB-728-T infusion

    Time frame: 28 days after the SB-728-T infusion of the last subject in each Cohort and up to 12 months

Secondary outcomes

  1. 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.

    Time frame: Up to 12 months after the last SB-728-T infusion

  2. 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.

    Time frame: Up to 12 months after the last SB-728-T infusion

  3. 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)

    Time frame: Up to 12 months after the last SB-728-T infusion

07

Results

Posted Apr 21, 2021

Participant flow

Participant flow — Overall Study
MilestoneCohort 1 - IV Cyclophosphamide 200 mgCohort 2 - IV Cyclophosphamide 0.5 g/m2Cohort 3 - IV Cyclophosphamide 1.0 g/m2Cohort 4 - IV Cyclophosphamide 2.0 g/m2Cohort 5 - IV Cyclophosphamide 1.5 g/m2
Started361133
Completed341133
Not completed02000
Withdrew: Withdrawal by subject02000

Outcome measures

PrimaryTreatment-emergent Adverse Events

Number of Participants with Treatment related Adverse Events in subjects who received any portion of the SB-728-T infusion

Time frame:
28 days after the SB-728-T infusion of the last subject in each Cohort and up to 12 months
Reported as:
Number · participants
Treatment-emergent Adverse Events
participantsCohort 1 - IV Cyclophosphamide 200 mgCohort 2 - IV Cyclophosphamide 0.5 g/m2Cohort 3 - IV Cyclophosphamide 1.0 g/m2Cohort 4 - IV Cyclophosphamide 2.0 g/m2Cohort 5 - IV Cyclophosphamide 1.5 g/m2
Treatment-emergent Adverse Events361133
SecondaryEffect 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.

Time frame:
Up to 12 months after the last SB-728-T infusion
Reported as:
Mean · cells 10^9/L
Effect of Escalating Doses of Cyclophosphamide on SB-728-T Engraftment as Measured by CCR5 Modified CD4 Cells in Blood.
cells 10^9/LCohort 1 - IV Cyclophosphamide 200 mgCohort 2 - IV Cyclophosphamide 0.5 g/m2Cohort 3 - IV Cyclophosphamide 1.0 g/m2Cohort 4 - IV Cyclophosphamide 2.0 g/m2Cohort 5 - IV Cyclophosphamide 1.5 g/m2
Effect of Escalating Doses of Cyclophosphamide on SB-728-T Engraftment as Measured by CCR5 Modified CD4 Cells in Blood.0.038 ± 0.04090.061 ± 0.04470.143 ± 0.10550.085 ± 0.01970.079 ± 0.0155
SecondaryEffect 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.

Time frame:
Up to 12 months after the last SB-728-T infusion
Reported as:
Mean · log copies/mL
Effect of SB-728-T on Plasma HIV-1 RNA Levels Following HAART Interruption
log copies/mLCohort 1 - IV Cyclophosphamide 200 mgCohort 2 - IV Cyclophosphamide 0.5 g/m2Cohort 3 - IV Cyclophosphamide 1.0 g/m2Cohort 4 - IV Cyclophosphamide 2.0 g/m2Cohort 5 - IV Cyclophosphamide 1.5 g/m2
Effect of SB-728-T on Plasma HIV-1 RNA Levels Following HAART Interruption0 ± 00.250 ± 0.50001.537 ± 1.39550.667 ± 0.57743.442 ± 1.1545
SecondaryChange 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)

Time frame:
Up to 12 months after the last SB-728-T infusion
Reported as:
Mean · cells 10^9/L
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)
cells 10^9/LCohort 1 - IV Cyclophosphamide 200 mgCohort 2 - IV Cyclophosphamide 0.5 g/m2Cohort 3 - IV Cyclophosphamide 1.0 g/m2Cohort 4 - IV Cyclophosphamide 2.0 g/m2Cohort 5 - IV Cyclophosphamide 1.5 g/m2
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)0.064 ± 0.13090.149 ± 0.3736-0.043 ± 0.17120.153 ± 0.32470.099 ± 0.3279

Adverse events

Collected over 1 year. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Cohort 1 - IV Cyclophosphamide 200 mg0/3 (0%)1/3 (33.3%)3/3 (100%)
Cohort 2 - IV Cyclophosphamide 0.5 g/m20/6 (0%)0/6 (0%)6/6 (100%)
Cohort 3 - IV Cyclophosphamide 1.0 g/m20/11 (0%)0/11 (0%)11/11 (100%)
Cohort 4 - IV Cyclophosphamide 2.0 g/m20/3 (0%)1/3 (33.3%)3/3 (100%)
Cohort 5 - IV Cyclophosphamide 1.5 g/m20/3 (0%)0/3 (0%)3/3 (100%)
Most frequent serious events
Most frequent serious events
EventCohort 1 - IV Cyclophosphamide 200 mgCohort 2 - IV Cyclophosphamide 0.5 g/m2Cohort 3 - IV Cyclophosphamide 1.0 g/m2Cohort 4 - IV Cyclophosphamide 2.0 g/m2Cohort 5 - IV Cyclophosphamide 1.5 g/m2
Cellulitis staphylococcalInfections and infestations1/30/60/110/30/3
Substance abusePsychiatric disorders0/30/60/111/30/3
Most frequent other events
Showing 10 of 90
Most frequent other events
EventCohort 1 - IV Cyclophosphamide 200 mgCohort 2 - IV Cyclophosphamide 0.5 g/m2Cohort 3 - IV Cyclophosphamide 1.0 g/m2Cohort 4 - IV Cyclophosphamide 2.0 g/m2Cohort 5 - IV Cyclophosphamide 1.5 g/m2
ChillsGeneral disorders2/34/63/113/30/3
NeutropeniaBlood and lymphatic system disorders0/30/60/113/32/3
Nervous system disorderNeoplasms benign, malignant and unspecified (incl cysts and polyps)2/36/64/111/32/3
AlopeciaSkin and subcutaneous tissue disorders0/30/63/113/33/3
HeadacheNeoplasms benign, malignant and unspecified (incl cysts and polyps)2/35/64/111/31/3
NauseaGastrointestinal disorders2/34/64/111/31/3
FatigueGeneral disorders1/32/63/110/32/3
Upper respiratory tract infectionInfections and infestations2/32/63/112/30/3
Bone painMusculoskeletal and connective tissue disorders0/30/60/112/30/3
Skin odour abnormalRespiratory, thoracic and mediastinal disorders1/32/65/112/31/3

Baseline characteristics

Age, Continuous
Age, Continuous(years)Cohort 1 - IV Cyclophosphamide 200 mgCohort 2 - IV Cyclophosphamide 0.5 g/m2Cohort 3 - IV Cyclophosphamide 1.0 g/m2Cohort 4 - IV Cyclophosphamide 2.0 g/m2Cohort 5 - IV Cyclophosphamide 1.5 g/m2Total
Mean44.7 ± 8.0843.2 ± 6.1141.5 ± 12.1335.3 ± 10.2150.0 ± 1.0042.5 ± 9.70
Sex: Female, Male
Sex: Female, Male(Participants)Cohort 1 - IV Cyclophosphamide 200 mgCohort 2 - IV Cyclophosphamide 0.5 g/m2Cohort 3 - IV Cyclophosphamide 1.0 g/m2Cohort 4 - IV Cyclophosphamide 2.0 g/m2Cohort 5 - IV Cyclophosphamide 1.5 g/m2Total
Female011002
Male35103324
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Cohort 1 - IV Cyclophosphamide 200 mgCohort 2 - IV Cyclophosphamide 0.5 g/m2Cohort 3 - IV Cyclophosphamide 1.0 g/m2Cohort 4 - IV Cyclophosphamide 2.0 g/m2Cohort 5 - IV Cyclophosphamide 1.5 g/m2Total
Hispanic or Latino023016
Not Hispanic or Latino3483220
Unknown or Not Reported000000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Cohort 1 - IV Cyclophosphamide 200 mgCohort 2 - IV Cyclophosphamide 0.5 g/m2Cohort 3 - IV Cyclophosphamide 1.0 g/m2Cohort 4 - IV Cyclophosphamide 2.0 g/m2Cohort 5 - IV Cyclophosphamide 1.5 g/m2Total
American Indian or Alaska Native000000
Asian001102
Native Hawaiian or Other Pacific Islander000000
Black or African American100001
White2692221
More than one race000000
Unknown or Not Reported001012
08

Study locations

11 sites
  • UCLA Care Center
    Los Angeles, California 90035, United States
  • Quest Clinical Research
    San Francisco, California 94115, United States
  • Circle CARE Center, LLC
    Norwalk, Connecticut 06850, United States
  • Orlando Immunology Center
    Orlando, Florida 32803, United States
  • Central West Clinical Research, Inc.
    Saint Louis, Missouri 63108, United States
  • Southwest CARE Center
    Santa Fe, New Mexico 87505, United States
  • Ricky K Hsu, MD, PC
    New York, New York 10011, United States
  • Central Texas Clinical Research
    Austin, Texas 78705, United States
  • North Texas Infectious Diseases Consultants
    Dallas, Texas 75246, United States
  • Gordon Crofoot, MD, PA
    Houston, Texas 77098, United States
  • Clinical Research Puerto Rico
    San Juan, 00909, Puerto Rico
09

References and documents

Study documents

  • Study protocol · Jan 30, 2014
  • Statistical analysis plan · Nov 23, 2020

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 24, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01543152
Lead sponsor
Sangamo Therapeutics
Responsible party
Sponsor
First posted
Mar 2, 2012
Start date
Dec 2011
Primary completion
Jul 7, 2017
Completion
Jul 7, 2017
Results posted
Apr 21, 2021
Last update
May 24, 2021

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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