Ignite Creation Date:
2024-05-06 @ 9:35 AM
Last Modification Date:
2024-10-26 @ 12:16 PM
Study NCT ID:
NCT03020524
Status:
COMPLETED
Last Update Posted:
2022-11-15
First Post:
2017-01-09
Brief Title:
Autologous CD4 T-Cells in HIV C34-CXCR4
Sponsor:
University of Pennsylvania
Organization:
University of Pennsylvania
Study Overview
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
Status Verified Date:
2022-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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
Detailed 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 333 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 03 subjects have a dose limiting toxicity DLT then the dose is escalated If 13 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 26 have DLT ie 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 08-1x109 transduced CD4T-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 24-3x109 transduced CD4 T-cells If no DLT occurs at that dose the final 3 subjects will receive the 3rd dose level of 08-1x1010 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
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 08-1x109 transduced CD4T-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 24-3x109 transduced CD4 T-cells If no DLT occurs at that dose the final 3 subjects will receive the 3rd dose level of 08-1x1010 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None