Autologous CD4 T-Cells in HIV (C34-CXCR4)

Hiv Clinical Trial

Official title: A Pilot Study to Evaluate the Safety and Tolerability of Escalating Doses of Autologous CD4 T-Cells Modified With Lentiviral Vector Expressing an HR2, C34-peptide Conjugated to the CXCR4 N-terminus in HIV-infected Subjects

Status Completed

Clinical Trial Summary

A single cohort, open-label pilot study of the safety and tolerability of a single infusion of autologous CD4+ T-cells genetically modified with an HR2, C34-peptide conjugated to the CXCR4 N-terminus using a lentiviral vector in HIV-infected subjects. This is a first in human study of C34-CXCR4 T cells

Clinical Trial Description

There will be a single cohort in this study, which consists of subjects with well-controlled HIV replication on HAART. Within this cohort will be 3 escalating doses of T-cell infusions. A modified 3+3+3 dose-escalation design will be followed, in which the standard dose-escalation algorithm is stopped when a maximum of 9 evaluable subjects or a DLT stopping point has been reached, whichever comes first. At each dose level, three patients are treated. For dose levels 1 and 2, if 0/3 subjects have a dose limiting toxicity (DLT), then the dose is escalated. If 1/3 has a DLT (grade 3 or higher unexpected, related adverse event [AE]) at a dose level then 3 additional patients are treated at that dosage before escalating, and if <2/6 have DLT (i.e. no additional DLT is observed) then the dose is escalated to the next planned dose level and patients treated until a maximum of 9 evaluable subjects has been reached. The study will comprise of 5 steps:

Step 1, all participants will undergo leukapheresis to obtain CD4 positive T-cells that will be genetically modified. A second leukapheresis and a rectal biopsy will provide baseline specimens to evaluate the size of the HIV reservoir

Step 2, all participants will receive a single infusion of C34-CXCR4-modified CD4+ T-cells at one of 3 dose levels. The first 3 subjects will receive dose level 1 of 0.8-1x109 transduced CD4+T-cells. Provided no dose limiting toxicity (DLT) is seen at the first dose level, the next 3 subjects will receive infusion at the 2nd dose level of 2.4-3x109 transduced CD4+ T-cells. If no DLT occurs at that dose, the final 3 subjects will receive the 3rd dose level of 0.8-1x1010 transduced CD4+ T-cells. In the event of a DLT (grade 3 or higher unexpected, related AE) recruitment will be paused pending DSMB decision.

Step 3 all participants will participate in a 16-week analytical treatment interruption beginning 4 weeks after T-cell infusion.

At the end of step 3 all participants will undergo mini-leukapheresis and rectal biopsy

Step 4 all participants will be advised to resume antiretroviral therapy and will be followed until plasma HIV RNA falls below the limit of detection.

In Step 5 all participants will undergo leukapheresis and rectal biopsy at 52 weeks post infusion. At the completion of the study, participants will be asked to participate in a long-term follow-up study as required by regulatory authorities. ;

Related Conditions & MeSH terms

• Hiv

• NCT number: NCT03020524
• Study type: Interventional
• Source: University of Pennsylvania
• Status: Completed
• Phase: Early Phase 1
• Start date: January 2017
• Completion date: March 2020