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NCT number NCT01967823
Study type Interventional
Source National Institutes of Health Clinical Center (CC)
Contact Jessica G Yingling, R.N.
Phone (866) 820-4505
Email ncisbirc@mail.nih.gov
Status Recruiting
Phase Phase 2
Start date September 25, 2013
Completion date July 2, 2018

Clinical Trial Summary

Background:

The NCI Surgery Branch has developed an experimental therapy for treating patients with cancer that involves taking white blood cells from the patient, growing them in the laboratory in large numbers, genetically modifying them, and then giving the cells back to the patient. In a previous study the NCI Surgery Branch used the anti-ESO-1 gene and a type of virus (retrovirus) to make these tumor fighting cells (anti-ESO-1 cells). About half of the patients who received this treatment experienced shrinking of their tumors. In this study, we are using a slightly different method of producing the anti-ESO-1 cells which we hope will be better in making the tumors shrink.

Objectives:

The purpose of this study is to see if these tumor fighting cells (genetically modified cells) that express the receptor for the ESO-1 molecule on their surface can cause tumors to shrink and to see if this treatment is safe.

Eligibility:

- Adults 18 years old and older with cancer that has the ESO-1 molecule on their tumors.

Design:

- Work up stage: Patients will be seen as an outpatient at the NIH clinical Center and undergo a history and physical examination, scans, x-rays, lab tests, and other tests as needed

- Leukapheresis: If the patients meet all of the requirements for the study they will undergo leukapheresis to obtain white blood cells to make the anti ESO-1 cells. {Leukapheresis is a common procedure which removes only the white blood cells from the patient.}

- Treatment: Once their cells have grown the patients will be admitted to the hospital for the conditioning chemotherapy, the anti-ESO-1 cells and aldesleukin. They will stay in the hospital for about 4 weeks for the treatment.

- Follow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1 year as long as their tumors are shrinking. Follow up visits take up to 2 days.


Clinical Trial Description

PRECIS

Background:

- We have constructed a single retroviral vector that contains both and <= chains of a murine T cell receptor (mTCR) that recognizes the NY-ESO-1 (ESO) tumor antigen, which can be used to mediate genetic transfer of this TCR with high efficiency.

- In co-cultures with HLA-A2 and ESO double positive tumors, anti-ESO mTCR transduced T cells secreted significant amounts of IFN- >= with high specificity.

Objectives:

Primary objectives:

- To determine whether the administration of anti-ESO mTCR-engineered peripheral blood lymphocytes (PBL) plus high-dose aldesleukin following a non-myeloablative lymphoid depleting preparative regimen may result in objective tumor regression in patients with metastatic cancers that express the ESO antigen.

Secondary objectives:

- Determine the in vivo survival of mTCR gene-engineered cells.

- Determine the toxicity profile of this treatment regimen.

Eligibility:

Patients who are HLA-A*0201 positive and 18 years of age or older must have

- Metastatic cancer including melanoma whose tumors express the ESO antigen;

- Patients must have previously received and have been a non-responder to or recurred after receiving standard care for metastatic disease;

Patients may not have:

- Contraindications for high dose aldesleukin administration.

Design:

- PBMC obtained by leukapheresis will be cultured in the presence of anti-CD3 (OKT3) and aldesleukin in order to stimulate T-cell growth.

- Transduction is initiated by exposure of cells to retroviral vector supernatant containing the anti- ESO mTCR genes. This mTCR targets the exact same epitope as the hTCR.

- All patients will receive a non-myeloablative lymphocyte depleting preparative regimen of cyclophosphamide and fludarabine.

- On day 0 patients will receive anti-ESO mTCR gene-transduced PBMC and then begin high dose aldesleukin.

- A complete evaluation of evaluable lesions will be conducted 6 weeks (+/- 2 weeks) following the administration of the cell product.

- The study will be conducted using a phase II optimal design (Simon R, Controlled Clinical Trials 10:1-10, 1989). The objective will be to determine if the combination of high dose aldesleukin, lymphocyte depleting chemotherapy, and anti-ESO TCR-gene engineered lymphocytes is able to be associated with a clinical response rate that can rule out 5% (p0=0.05) in favor of a modest 20% PR + CR rate (p1=0.20).

- A total of up to 43 patients may be enrolled (41, plus allowing for up to 2 non-evaluable patients).


Study Design


Related Conditions & MeSH terms


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