Don't get left behind! The modernized ClinicalTrials.gov is coming. Check it out now.
Say goodbye to ClinicalTrials.gov!
The new site is coming soon - go to the modernized ClinicalTrials.gov
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety Study of Zinc Finger Nuclease CCR5-modified Hematopoietic Stem/Progenitor Cells in HIV-1 Infected Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02500849
Recruitment Status : Active, not recruiting
First Posted : July 17, 2015
Last Update Posted : March 10, 2023
Sponsor:
Collaborators:
Sangamo Therapeutics
California Institute for Regenerative Medicine (CIRM)
Information provided by (Responsible Party):
City of Hope Medical Center

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
The purpose of the study is to evaluate the safety and feasibility of administering SB-728mR-HSPC after conditioning with busulfan.

Condition or disease Intervention/treatment Phase
HIV Genetic: SB-728mR-HSPC Infusion 3 days following busulfan conditioning Phase 1

Detailed Description:
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.
Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 10, 2016
Actual Primary Completion Date : September 20, 2020
Estimated Study Completion Date : December 10, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Busulfan

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Cohort 1:
target busulfan AUC levels: 8,000 µM*min (+/- 1,000)
 Genetic: SB-728mR-HSPC Infusion 3 days following busulfan conditioning
Other Name: busulfan
Experimental: Cohort 2:
busulfan AUC levels: 12,000 µM*min (+/- 1,000)
 Genetic: SB-728mR-HSPC Infusion 3 days following busulfan conditioning
Other Name: busulfan


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Toxicity in subjects who received SB-728mR-HSPC after each busulfan dose level [ Time Frame: 18 months ]

Secondary Outcome Measures :
  1. Number of CD34+ HSPC collected, gene modified, and released throughout the manufacturing process [ Time Frame: Approximately first 1-2 months on study ]

Other Outcome Measures:
  1. Detection of CCR5 modified HSPC in bone marrow [ Time Frame: Up to Month 12 ]
  2. Time to hematological recovery as measured by neutrophil and platelet engraftment time [ Time Frame: Up to Year 5 ]
  3. Changes in CD4+ T-cell percentage after SB-728mR-HSPC infusion [ Time Frame: Up to Year 5 ]
  4. Changes in CD4+ T-cell number after SB-728mR-HSPC infusion [ Time Frame: Up to Year 5 ]
  5. Changes in CD4/CD8 ratio after SB-728mR-HSPC infusion [ Time Frame: Up to Year 5 ]
  6. Detection of CCR5-modified PBMC in blood over time [ Time Frame: Up to Year 5 ]
  7. HIV-1 RNA levels in plasma during the treatment interruption of antiretroviral medicines [ Time Frame: ATI Day 0 and weeks 2, 4, 6, 8, 10, 12, 14, 16 and 28 ]
  8. Longitudinal changes of proviral DNA in PBMC [ Time Frame: 18 months ]
  9. Pharmacokinetic analysis of busulfan (AUC levels) [ Time Frame: pre-busulfan and at 15, 30, 60, 180 and 240 min after end of infusion ]

Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 10^6 CD34+ cells/kg in two aphereses.
  • The SB-728mR-HSPC product passed all release testing

Exclusion Criteria:

  • 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.
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02500849


Locations
Layout table for location information
United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
UCLA CARE Center
Los Angeles, California, United States, 90035
Mills Clinical Research
Los Angeles, California, United States, 90069
Quest Clinical Research
San Francisco, California, United States, 94115
United States, Connecticut
Circle CARE Center, LLC
Norwalk, Connecticut, United States, 06850
Sponsors and Collaborators
City of Hope Medical Center
Sangamo Therapeutics
California Institute for Regenerative Medicine (CIRM)
Investigators
Layout table for investigator information
Principal Investigator: Amrita Y. Krishnan, MD City of Hope Medical Center
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT02500849    
Other Study ID Numbers: 14017
First Posted: July 17, 2015    Key Record Dates
Last Update Posted: March 10, 2023
Last Verified: March 2023
Keywords provided by City of Hope Medical Center:
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
Additional relevant MeSH terms:
Layout table for MeSH terms
Busulfan
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
 Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Antineoplastic Agents
Myeloablative Agonists