Summary

for people ages 18-75 (full criteria)
at UCLA
study started
estimated completion:
Ronald Mitsuyasu (ucla)

Description

Summary

The purpose of the study is to evaluate the safety and feasibility of administering SB-728mR-HSPC after conditioning with busulfan.

Official Title

A Pilot Study to Evaluate the Feasibility, Safety and Engraftment of Zinc Finger Nuclease (ZFN) CCR5 Modified CD34+ Hematopoietic Stem/Progenitor Cells (SB-728mR-HSPC) in HIV-1 (R5) Infected Patients

Details

The objective of the study is to evaluate the safety and feasibility of giving autologous SB-728mR-HSPC to HIV-1 (R5) infected patients who are being treated with cART and have undetectable virus but suboptimal CD4+ cell levels. To strengthen the possibility that CCR5-disrupted HSPCs engraft, patients will receive either a two- or three-day (Cohort 1 or Cohort 2) course of busulfan (dose targeting AUC of 4000 µM/day) before being infused with the genetically modified cells. At 9-12 months after SB-728mR-HSPC infusion, subjects who are aviremic with CD4 cell counts ≥600 cells/µL and have ≥1% CCR5-modified CD4 cells within the peripheral blood detected by pentamer PCR will undergo an ATI.

Keywords

HIV Gene therapy Acquired Immunodeficiency Syndrome HIV Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Busulfan Pharmacologic Actions SB-728mR-HSPC Infusion 3 days following busulfan conditioning

Eligibility

You can join if…

Open to people ages 18-75

  • Maximum age 75 years for cohort 1 and 65 years for cohort 2.
  • HIV-1 R5 seropositive with no evidence of CXCR4-tropic virus.
  • On cART with undetectable HIV-1 (<20 gc/ml HIV-1 RNA) for at least 12 months prior to screening evaluations.
  • CD4+ T-cell counts ≥200 cells/µL and ≤750 cells/µL.
  • No psychosocial conditions that would hinder study compliance and follow-up.
  • Absence of clinically significant cardiomyopathy, congestive heart failure.

Secondary Eligibility Criteria (for registration):

  • Complete G-CSF/Plerixafor mobilization of HSPC.
  • Collect ≥7.5 x 106 CD34+ cells/kg in two aphereses.

  • The SB-728mR-HSPC product passed all release testing

You CAN'T join if...

  • Use of AZT or maraviroc in the cART regimen.
  • History of significant hematologic diseases such as leukemia, myelodysplasia,coagulopathy, and thromboembolism.
  • Any AIDS-related opportunistic infection occurring within the past year such as tuberculosis, cryptococcosis and for which treatment has been unsuccessful as determined by the Principal Investigator.
  • AIDS-related syndromes, infectious or otherwise, if perceived to cause excessive risk for morbidity post-HSPC infusion, as determined by the Principal Investigator.
  • Patients with active HBV or HCV infection, i.e., HBV DNA and HCV RNA in blood, are excluded. Those with inactive, but past infection with HBV (positive HBV surface antigen or HBV surface antibody) or inactive HCV (positive HCV antibody), must have no cirrhosis, as determined by abdominal ultrasound with elastography.
  • Active CMV retinitis or other active CMV-related organ dysfunction.
  • CXCR4-tropic virus.
  • Pregnant or nursing women.
  • Any history of HIV-associated encephalopathy; dementia of any kind; seizures in the past 12 months; any perceived inability to directly provide informed consent.
  • Participants may not be receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy. Participation in prior investigational drug or medical device study within the previous 45 days.
  • Current or history of immunomodulatory agent or steroid use.
  • Prior therapy with HIV vaccine or gene therapy product.
  • History of alcohol or substance abuse for the previous 12 months.
  • Participants with active malignancies. However, participants with skin cancers, namely basal cell or squamous cell carcinoma, and malignancies treated with curative intent having no known active disease present for ≥2 years, may be eligible.

Locations

  • UCLA CARE Center accepting new patients
    Los Angeles California 90035 United States
  • Quest Clinical Research accepting new patients
    San Francisco California 94115 United States
  • Mills Clinical Research accepting new patients
    Los Angeles California 90069 United States

Lead Scientist

  • Ronald Mitsuyasu (ucla)
    Professor, Medicine. Authored (or co-authored) 72 research publications

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
City of Hope Medical Center
ID
NCT02500849
Phase
Phase 1
Study Type
Interventional
Last Updated