Ignite Creation Date:
2025-12-24 @ 4:07 PM
Ignite Modification Date:
2026-02-25 @ 8:50 PM
Study NCT ID:
NCT02489266
Status:
WITHDRAWN
Last Update Posted:
2017-07-27
First Post:
2015-07-02
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
In Vivo Persistence of Adoptively-Transferred TIL Cultured With Akti in People With Metastatic Melanoma
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
A Phase I Trial for the Evaluation of the In Vivo Persistence of Adoptively-transferred Tumor-Infiltrating Lymphocytes Cultured With a Pharmacologic Inhibitor of AKT in Patients With Metastatic Melanoma
Status:
WITHDRAWN
Status Verified Date:
2016-06-29
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:
Background:
\- One cancer therapy involves taking white blood cells from a person, changing them in a lab, and then giving the cells back to the person. These cells are called tumor infiltrating lymphocytes (TIL). Researchers want to grow some of the TIL cells with the drug Akti to see if they live longer than those grown without it.
Objectives:
\- To see if TIL cells grown with Akti live longer than those grown without it.
Eligibility:
\- Adults 18 70 with metastatic melanoma
Design:
* Participants will:
* Be screened with tests including scans, x-rays, heart and lung tests, blood and urine tests, and a \<TAB\>possible colonoscopy.
* Have tumor surgery or biopsy.
* Have a large catheter inserted into a vein in the upper chest.
* Receive leukapheresis for 4 5 hours. Blood is removed through a needle in an arm. White blood cells \<TAB\>are removed. The rest of the blood is returned by needle in the other arm.
* The cells will be changed in a laboratory.
* Participants will check into the hospital and:
* For 5 days, get 1 2 chemotherapy drugs by catheter.
* For 1 3 days, get the changed cells by catheter.
* For several days, get 2 drugs to stimulate cells, one by injection, the other by catheter.
* For 7 12 days, recover in the hospital.
* After treatment, participants will:
* Take an antibiotic and antiviral for at least 6 months.
* Return to NIH for several 2-day visits for a few years. At each visit, participants will have lab tests, imaging studies, and a physical exam. At some visits, they may have leukapheresis or blood tests.
\- One cancer therapy involves taking white blood cells from a person, changing them in a lab, and then giving the cells back to the person. These cells are called tumor infiltrating lymphocytes (TIL). Researchers want to grow some of the TIL cells with the drug Akti to see if they live longer than those grown without it.
Objectives:
\- To see if TIL cells grown with Akti live longer than those grown without it.
Eligibility:
\- Adults 18 70 with metastatic melanoma
Design:
* Participants will:
* Be screened with tests including scans, x-rays, heart and lung tests, blood and urine tests, and a \<TAB\>possible colonoscopy.
* Have tumor surgery or biopsy.
* Have a large catheter inserted into a vein in the upper chest.
* Receive leukapheresis for 4 5 hours. Blood is removed through a needle in an arm. White blood cells \<TAB\>are removed. The rest of the blood is returned by needle in the other arm.
* The cells will be changed in a laboratory.
* Participants will check into the hospital and:
* For 5 days, get 1 2 chemotherapy drugs by catheter.
* For 1 3 days, get the changed cells by catheter.
* For several days, get 2 drugs to stimulate cells, one by injection, the other by catheter.
* For 7 12 days, recover in the hospital.
* After treatment, participants will:
* Take an antibiotic and antiviral for at least 6 months.
* Return to NIH for several 2-day visits for a few years. At each visit, participants will have lab tests, imaging studies, and a physical exam. At some visits, they may have leukapheresis or blood tests.
Detailed Description:
Background:
* Adoptive cellular immunotherapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) can mediate regression of bulky metastatic melanoma when administered with high-dose aldesleukin (IL-2) following a non-myeloablative lymphodepleting chemotherapy preparative regimen consisting of cyclophosphamide and fludarabine.
* Regression of tumor in mouse models and humans strongly correlates with anti-tumor T cells that exhibit features of immunologic memory and have a capacity to persist for long periods after adoptive-transfer into tumor-bearing hosts.
* In our preclinical work with TIL, we have identified a pharmacologic inhibitor of AKT that promotes features of immunologic memory in TIL (as evidenced by transcriptomic, proteomic, metabolomic, and functional assays described in the Background section). Consistently, AKT inhibition of human TIL significantly enhances persistence after adoptive-transfer into an immunodeficient mouse model.
* We therefore aim to evaluate whether pharmacologic inhibition of AKT in TIL may enhance persistence after adoptive-transfer into patients with advanced melanoma.
Objectives:
* Primary objective:
* To determine whether ACT using TIL cultured in a pharmacologic inhibitor of AKT (during ex vivo expansion) results in enhanced in vivo persistence of TIL after adoptive transfer into autologous patients with advanced melanoma.
* Secondary objectives:
* Determine the toxicity profile of this treatment regimen.
* Determine whether ACT using a combination of AKTi-treated and conventional TIL can mediate tumor regression by RECIST (Response Evaluation Criteria in Solid Tumors) guidelines in patients with advanced melanoma.
Eligibility:
* Age greater than or equal to 18 and less than or equal to 70 years
* Evaluable metastatic melanoma
* Metastatic melanoma lesion suitable for surgical resection for the preparation of TIL
* No contraindications to high-dose aldesleukin administration
* No concurrent major medical illnesses or any form of immunodeficiency
Design:
* Patients with metastatic melanoma will undergo ACT in conventional manner, with the exception that half of tumor fragments from which TIL are isolated will be cultured in the presence of a pharmacologic AKT inhibitor. Prior to infusion of TIL, the AKT inhibitor (hereafter AKTi) will be washed from the therapeutic TIL product and will not be systemically administered. Each patient will receive a 1:1 mixture of conventional TIL and AKTi-treated TIL. To evaluate persistence of AKTi-treated and conventional TIL after adoptive co-transfer, we will perform high-throughput deep sequencing of the TCR V-beta CDR3 region of TIL from the infusion-bag and from peripheral blood when sufficient lymphocyte reconstitution (\>200 lymphocytes/microliter) has occurred and approximately 4-6 weeks after infusion.
* Up to 20 patients may be enrolled over 20-24 months.
* Adoptive cellular immunotherapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) can mediate regression of bulky metastatic melanoma when administered with high-dose aldesleukin (IL-2) following a non-myeloablative lymphodepleting chemotherapy preparative regimen consisting of cyclophosphamide and fludarabine.
* Regression of tumor in mouse models and humans strongly correlates with anti-tumor T cells that exhibit features of immunologic memory and have a capacity to persist for long periods after adoptive-transfer into tumor-bearing hosts.
* In our preclinical work with TIL, we have identified a pharmacologic inhibitor of AKT that promotes features of immunologic memory in TIL (as evidenced by transcriptomic, proteomic, metabolomic, and functional assays described in the Background section). Consistently, AKT inhibition of human TIL significantly enhances persistence after adoptive-transfer into an immunodeficient mouse model.
* We therefore aim to evaluate whether pharmacologic inhibition of AKT in TIL may enhance persistence after adoptive-transfer into patients with advanced melanoma.
Objectives:
* Primary objective:
* To determine whether ACT using TIL cultured in a pharmacologic inhibitor of AKT (during ex vivo expansion) results in enhanced in vivo persistence of TIL after adoptive transfer into autologous patients with advanced melanoma.
* Secondary objectives:
* Determine the toxicity profile of this treatment regimen.
* Determine whether ACT using a combination of AKTi-treated and conventional TIL can mediate tumor regression by RECIST (Response Evaluation Criteria in Solid Tumors) guidelines in patients with advanced melanoma.
Eligibility:
* Age greater than or equal to 18 and less than or equal to 70 years
* Evaluable metastatic melanoma
* Metastatic melanoma lesion suitable for surgical resection for the preparation of TIL
* No contraindications to high-dose aldesleukin administration
* No concurrent major medical illnesses or any form of immunodeficiency
Design:
* Patients with metastatic melanoma will undergo ACT in conventional manner, with the exception that half of tumor fragments from which TIL are isolated will be cultured in the presence of a pharmacologic AKT inhibitor. Prior to infusion of TIL, the AKT inhibitor (hereafter AKTi) will be washed from the therapeutic TIL product and will not be systemically administered. Each patient will receive a 1:1 mixture of conventional TIL and AKTi-treated TIL. To evaluate persistence of AKTi-treated and conventional TIL after adoptive co-transfer, we will perform high-throughput deep sequencing of the TCR V-beta CDR3 region of TIL from the infusion-bag and from peripheral blood when sufficient lymphocyte reconstitution (\>200 lymphocytes/microliter) has occurred and approximately 4-6 weeks after infusion.
* Up to 20 patients may be enrolled over 20-24 months.
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 15-C-0153 | None | None | View |