Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
Description Module path is as follows:
Study -> Protocol Section -> Description Module
Description Module
Ignite Creation Date:
2025-12-24 @ 7:37 PM
Ignite Modification Date:
2025-12-24 @ 7:37 PM
NCT ID:
NCT03089203
Brief Summary:
This is a single center, single arm Phase I study to establish the safety and feasibility of intravenously administered lentivirally transduced dual PSMA-specific/ TGFβ-resistant CAR modified autologous T cells (CART-PSMA-TGFβRDN cells) in patients with metastatic castrate resistant prostate cancer.
Detailed Description:
This is a Phase I study evaluating the safety and feasibility of lentivirally transduced PSMA-TGFβRDN autologous CAR T cells administered with and without cyclophosphamide/fludarabine lymphodepleting chemotherapy in a 3+3 dose escalation design. Subjects must receive the dose of CART-PSMA-TGFβRDN cells as per their cohort assignment in order to be considered evaluable for DLT assessments at that dose level. Subjects who do not receive CART-PSMA-TGFβRDN cells as per their cohort assignment will not be evaluable for DLT assessments/MTD determination, however they will still be followed per protocol and will be included in the overall safety analysis, as well as the analysis of secondary and exploratory endpoints. Subjects who enroll but do not receive CART-PSMA-TGFβRDN cells will be removed from the study and replaced.
Up to 5 dosing cohorts will be explored as follows:
* Cohort 1 subjects (N=3 or 6): will receive a single dose of 1-3 x 107/m2 lentivirally transduced CART-PSMA-TGFβRDN cells on day 0 without any conditioning chemotherapeutic regimen. If 1 DLT/3 subjects occurs, the study will enroll an additional 3 subjects at this dose level. If 0 DLT/3 subjects or 1 DLT/6 subjects occurs, the study will advance to Cohort 2. If 2 DLT/3 subjects occurs at dose of 1-3 x 107/m2 cells, then enrollment in this Cohort will be stopped and the dose will be de-escalated by 10-fold to 1-3 x 106 cells/m2 (Cohort -1). In this situation, up to 6 subjects will be enrolled in Cohort -1.
* Cohort 2 subjects (N=3 or 6): will receive a single dose of 1-3 x 108/m2 lentivirally transduced CART-PSMA-TGFβRDN cells on day 0 without any conditioning chemotherapeutic regimen. If 1 DLT/3 subjects occurs, the study will enroll an additional 3 subjects at this dose level. If 0 DLT/3 subjects or 1 DLT/6 subjects occurs, the study will advance toIf 2 DLT/3 subjects occur, then the study will stop and declare maximum tolerated dose (MTD).
Cohorts 1 and 2 were originally designed to identify the MTD of CART-PSMA-TGFβRDN cells. The highest dose level where only 0/3 or 1/6 DLTs were observed in a given cohort will be defined as the MTD for evaluation in Cohort 3.
COHORT 3 CLOSED WITH PROTOCOL V10
* Cohort 3 subjects (N=3 to 9): will receive a single dose of lentivirally transduced CART-PSMA-TGFβRDN cells at the MTD (established by Cohorts 1-2) on day 0, following lymphodepleting chemotherapy with cyclophosphamide 300 mg/m2/day and fludarabine 30 mg/m2/day given over 3 days; lymphodepleting chemotherapy will be scheduled such that the last day of chemotherapy is 3 days (± 1 day) prior to the infusion of CART-PSMA-TGFβRDN cells. This treatment regimen will be evaluated as follows:
* If 0 DLT /3 subjects occur, the study will enroll an additional 6 patients to confirm further evaluate the safety of this treatment regimen.
* If 1 DLT/3 subjects occurs, the study will enroll an additional 3 subjects at this dose level to further evaluate safety. If 1 DLT/6 subjects and the safety of this treatment regimen is established, another 3 subjects may be enrolled to further evaluate the safety of this treatment regimen.
* If 2 DLT/3 subjects or 2 DLT/6 subjects occurs, then enrollment into this cohort will be stopped and the CART-PSMA-TGFβRDN dose will be de-escalated to 1x107/m2 CART-PSMA-TGFβRDN cells with lymphodepleting chemotherapy (Cohort -3). At least 3 subjects would be treated in the Cohort -3 de-escalation cohort.
* Cohort -3 subjects (N=3 to 6): will open in the event of unacceptable toxicity in Cohort 3. Subjects enrolled into this cohort will receive a single dose of 1-3 x 107/m2 lentivirally transduced CART-PSMA-TGFβRDN cells on day 0, following lymphodepleting chemotherapy with cyclophosphamide 300 mg/m2/day and fludarabine 30 mg/m2/day given over 3 days; lymphodepleting chemotherapy will be scheduled such that the last day of chemotherapy is 3 days (± 1 day) prior to the infusion of CART-PSMA-TGFβRDN cells. Up to 6 subjects will be treated in this dose de-escalated cohort to demonstrate the safety of this regimen.
Once the safety of the Cohort -3 dosing regimen has been established, a new dose escalation Cohort 4 will be opened to enrollment. The 1st three infusions in Cohort 4 will be staggered by 28 days to allow for the assessment of DLTs. If no safety concerns are identified in the first three subjects within this cohort, subsequent infusions within Cohort 4 will be staggered by at least 14 days.
• Cohort 4 subjects (N=3 to 6): Subjects enrolled into this cohort will receive a single dose of 0.70-1.00 x 108 lentivirally transduced CART-PSMA-TGFβRDN cells on Day 0, following lymphodepleting chemotherapy with cyclophosphamide 300 mg/m2/day and fludarabine 30 mg/m2/day given over 3 days. Lymphodepleting chemotherapy will be scheduled such that the last day of chemotherapy is 3 days (± 1 day) prior to the infusion of CART-PSMA-TGFβRDN cells.
* If 1 DLT/3 subjects occurs, the study will enroll an additional 3 subjects at this dose level. If 1 DLT/6 subjects occurs, this dose level will be established as safe; and the safety of the CART-PSMA-TGFβRDN cells may continue to be further explored as part of a subsequent expansion amendment.
* If 0 DLT/3 subjects occurs, the study will enroll an additional 3 subjects at this dose level to further evaluate safety. If 0 DLT/6 subjects or 1 DLT/6 subjects occurs, this dose level will be established as safe; and the safety of the CART-PSMA-TGFβRDN cells may continue to be further explored as part of a subsequent expansion amendment. .
* If 2 DLTs occur at any time, enrollment in this cohort will be stopped and the study will be paused for additional investigation.
At the investigator's discretion, subjects may receive "retreatment" with CART-PSMA-TGFβRDN cells at any point after Day 28, provided that safety of the cohort-defined treatment regimen has been established.
Study:
NCT03089203
Study Brief:
Protocol Section:
NCT03089203