NCT01457131

Modified White Blood Cells That Secrete IL-2 and Express a Protein That Targets the ESO-1tumor Protein for Metastatic Cancer

Terminated Phase 1 Last updated 8 January 2019

What this trial tests

Phase 1 trial testing Fludarabine in Metastatic Cancer in 2 participants. Terminated before completion.

Timeline

6 October 2011

Primary endpoint
7 August 2013

7 August 2013

Quick facts

Lead sponsor	National Cancer Institute (NCI)
Phase	Phase 1
Status	Terminated
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	2
Start date	6 October 2011
Primary completion	7 August 2013
Estimated completion	7 August 2013
Sites	1 location across United States

Drugs / interventions tested

• Fludarabine (FLUDARABINE) — full drug profile →
• Cyclophosphamide (cyclophosphamide) — full drug profile →
• IL-12 & Anti-NY ESO1 TCR PBL

Conditions studied

• Metastatic Cancer — all drugs for Metastatic Cancer →
• Metastatic Melanoma — all drugs for Metastatic Melanoma →
• Metastatic Renal Cancer — all drugs for Metastatic Renal Cancer →

Sponsor

National Cancer Institute (NCI)

Who can join

Adults 18 to 99, any sex, with Metastatic Cancer or Metastatic Melanoma. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Background:

\- A new cancer treatment involves collecting white blood cells from an individual, modifying them to secrete IL-2 and target the ESO-1 protein expressed on some cancers, and returning them to the body. The cells may then be able to seek out the cancer cells and destroy them. Some kinds of cancer contain a protein called ESO-1, which is found on the surface of the cells. Doctors want to modify white blood cells to have an anti-ESO-1 effect, and use them to treat the cancer that has the ESO-1. In addition to adding genes that target the ESO-1 protein to the cells, the genes for IL-12 are added to the cells. IL-12 is a protein that stimulates the immune system. This type of therapy is called gene transfer.

Objectives:

\- To test the safety and effectiveness of anti-ESO-1/IL-12 white blood cells against metastatic cancer.

Eligibility:

\- Individuals at least 18 years of age who have metastatic cancer that expresses ESO-1 and has not responded to standard treatments.

Design:

* Participants will be screened with a medical history and physical exam. They will also have blood tests and imaging studies.
* Participants will have leukapheresis about a month before the treatment to collect white blood cells.
* They will have chemotherapy 5 days before the treatment to suppress the immune system, and prepare the body for the anti-ESO-1/IL-12 cells.
* The anti-ESO-1/IL-12 cells will be given as an infusion.
* Participants will be monitored in the hospital during their recovery from the treatment.
* Participants will have regular followup exams every 1 to 6 months. The exams will include blood tests, imaging studies, and other studies.

Due to toxicities seen with the regimen, it was decided not to pursue the phase 2 portion of the study.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. The basic principles of chimeric antigen receptor design.
   Sadelain M, Brentjens R, Rivière I. · · 2013 · cited 1144× · PMID 23550147 · DOI 10.1158/2159-8290.cd-12-0548
2. Interleukin 12: still a promising candidate for tumor immunotherapy?
   Lasek W, Zagożdżon R, Jakobisiak M. · · 2014 · cited 366× · PMID 24514955 · DOI 10.1007/s00262-014-1523-1
3. Anchoring of intratumorally administered cytokines to collagen safely potentiates systemic cancer immunotherapy.
   Momin N, Mehta NK, Bennett NR, Ma L, et al · · 2019 · cited 176× · PMID 31243150 · DOI 10.1126/scitranslmed.aaw2614
4. Understanding the Mechanisms of Resistance to CAR T-Cell Therapy in Malignancies.
   Cheng J, Zhao L, Zhang Y, Qin Y, et al · · 2019 · cited 112× · PMID 31824840 · DOI 10.3389/fonc.2019.01237
5. The biological basis and clinical symptoms of CAR-T therapy-associated toxicites.
   Titov A, Petukhov A, Staliarova A, Motorin D, et al · · 2018 · cited 91× · PMID 30181581 · DOI 10.1038/s41419-018-0918-x
6. Advancing CAR T-Cell Therapy for Solid Tumors: Lessons Learned from Lymphoma Treatment.
   Titov A, Valiullina A, Zmievskaya E, Zaikova E, et al · · 2020 · cited 54× · PMID 31947775 · DOI 10.3390/cancers12010125
7. Increasing the safety and efficacy of chimeric antigen receptor T cell therapy.
   Li H, Zhao Y. · · 2017 · cited 51× · PMID 28434147 · DOI 10.1007/s13238-017-0411-9
8. Immune Cell Hacking: Challenges and Clinical Approaches to Create Smarter Generations of Chimeric Antigen Receptor T Cells.
   Elahi R, Khosh E, Tahmasebi S, Esmaeilzadeh A. · · 2018 · cited 49× · PMID 30108584 · DOI 10.3389/fimmu.2018.01717