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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Sangamo Biosciences
ClinicalTrials.gov Identifier:
NCT01543152
First received: March 1, 2012
Last updated: August 22, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
HIV
Genetic: SB-728-T
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Sangamo Biosciences:

Primary Outcome Measures:
  • Treatment related Adverse Events on subjects who received cyclophosphamide prior to 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Effect of escalating doses of cyclophosphamide on SB-728-T engraftment as measured by pentamer PCR [ Time Frame: Up to 12 months after the last SB-728-T infusion ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Change in CD4+ T-cell counts in peripheral blood after treatment with SB-728-T [ Time Frame: Up to 12 months after the last SB-728-T infusion ] [ Designated as safety issue: No ]

Estimated Enrollment: 18
Study Start Date: December 2011
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 0.5 g/m2
Other Name: 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 1.0 g/m2
Other Name: cyclophosphamide

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01543152

Locations
United States, California
UCLA Care Center
Los Angeles, California, United States, 90035
Quest Clinical Research
San Francisco, California, United States, 94115
United States, Connecticut
Circle CARE Center, LLC
Norwalk, Connecticut, United States, 06850
United States, Florida
Orlando Immunology Center
Orlando, Florida, United States, 32803
United States, Missouri
Central West Clinical Research, Inc.
St Louis, Missouri, United States, 63108
United States, New Mexico
Southwest CARE Center
Santa Fe, New Mexico, United States, 87505
United States, New York
Ricky K Hsu, MD, PC
New York, New York, United States, 10011
United States, Texas
Gordon Crofoot, MD, PA
Houston, Texas, United States, 77098
Puerto Rico
Clinical Research Puerto Rico
San Juan, Puerto Rico, 00909
Sponsors and Collaborators
Sangamo Biosciences
Investigators
Study Director: Winson Tang, M.D. Sangamo BioSciences, Inc.
  More Information

No publications provided

Responsible Party: Sangamo Biosciences
ClinicalTrials.gov Identifier: NCT01543152     History of Changes
Other Study ID Numbers: SB-728-1101
Study First Received: March 1, 2012
Last Updated: August 22, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Sangamo Biosciences:
HIV
autologous cell therapy
cyclophosphamide

Additional relevant MeSH terms:
Cyclophosphamide
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014