Clinical Trials Logo

Clinical Trial Summary

Background:

The NCI Surgery Branch has developed an experimental therapy for treating patients with melanoma 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 selected for a specific cell type, 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 melanoma tumors to shrink and to see if this treatment is safe.

Eligibility:

-Adults 18 and older with cancer that has the ESO-1 molecule on tumor surfaces

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

Background:

- A T cell receptor (TCR) that recognizes the NY-ESO-1 (ESO) tumor/testes antigen has been cloned into a retrovirus and can be used to genetically modify human peripheral blood lymphocytes (PBL) so they recognize HLA-A2+, ESO+ tumors

- PBL expressing the anti-ESO TCR have been administered with aldesleukin with or without ALVAC vaccine to 21 patients with melanoma following lymphodepleting chemotherapy at the Surgery Branch, resulting in objective tumor regression (complete or partial regression) in ten patients (47%).

- In animal models using murine cells and in experiments with human T cells in vitro, T cell subsets expressing the lymphoid homing and differentiation marker CD62L, including na(SqrRoot) ve T cells (TNaive), stem cell memory T cells (TSCM), and central memory T cells (TCM), were shown to have superior attributes compared to whole PBL and CD62L- PBL for adoptive cell therapy, including superior persistence following transfer in vivo.

Objectives:

Primary objective:

- To determine whether the administration of anti-ESO TCR engineered CD62L+-derived lymphocytes plus high-dose aldesleukin following a non-myeloablative lymphodepleting preparative regimen can result in an objective regression rate (PR + CR) of melanoma tumors.

Secondary objectives:

- Determine the persistence of genetically engineered, adoptively transferred CD62L+ derived lymphocytes.

- Determine the toxicity profile of this treatment regimen.

Eligibility:

Patients who are:

- HLA-A*0201 positive

- 18 years of age or older

- Have metastatic melanoma that expresses the ESO antigen

Patients may not have:

- Contraindications for high dose aldesleukin administration.

Design:

- PBMC will be obtained by leukapheresis and will undergo positive selection for CD62L using a CliniMACS magnetic cell separation apparatus to enrich for the less differentiated TNaive, TSCM, and TCM subsets.

- The enriched CD62L+ lymphocytes will be cultured in the presence of anti-CD3 (OKT3) and aldesleukin in order to stimulate T-cell growth, then transduced with the anti-ESO TCR.

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

- On day 0 patients will receive anti-ESO TCR gene-transduced CD62L+ -derived lymphocytes 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 primary objective will be efficacy. The study will be conducted using a phase II optimal design (Simon R, Controlled Clinical Trials 10:1-10, 1989) in order to rule out an unacceptably low 40% overall response rate (p0=0.40) in favor of an improved response rate of 65% (p1=0.65). This study will initially enroll 11 evaluable patients, and if 0 to 5 of the 11 have a response, then no further patients will be accrued. If 6 or more of the first 11 patients have a response, then accrual would continue until a total of 20 patients have been enrolled. If there were 11 or more responses in 20 patients (55%), this would be sufficiently interesting to warrant further study in later trials. To allow for a very small number of inevaluable patients, the accrual ceiling will be set at 22 patients. ;


Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


NCT number NCT02062359
Study type Interventional
Source National Institutes of Health Clinical Center (CC)
Contact
Status Completed
Phase Phase 2
Start date February 2014
Completion date February 2016

See also
  Status Clinical Trial Phase
Recruiting NCT05094804 - A Study of OR2805, a Monoclonal Antibody Targeting CD163, Alone and in Combination With Anticancer Agents Phase 1/Phase 2
Enrolling by invitation NCT00068003 - Harvesting Cells for Experimental Cancer Treatments
Recruiting NCT05798611 - Study of ART0380 in Patients With Biologically Selected Solid Tumors Phase 2
Not yet recruiting NCT04931420 - Study Comparing Standard of Care Chemotherapy With/ Without Sequential Cytoreductive Surgery for Patients With Metastatic Foregut Cancer and Undetectable Circulating Tumor-Deoxyribose Nucleic Acid Levels Phase 2
Recruiting NCT05566574 - A Study of RP-3500 in Combination With Standard Radiation Therapy in People With Solid Tumor Cancer Phase 1/Phase 2
Recruiting NCT05036681 - A Phase II Study of Futibatinib and Pembrolizumab in Metastatic Microsatellite Stable Endometrial Carcinoma Phase 2
Withdrawn NCT00005030 - SCH 66336 Before Surgery in Treating Patients With Colorectal Cancer That Has Metastasized to the Liver Phase 1
Recruiting NCT05525858 - KPMNG Study of MOlecular Profiling Guided Therapy Based on Genomic Alterations in Advanced Solid Tumors II
Recruiting NCT04085029 - Role of Ablative Radiotherapy in the Management of Metastatic Disease: A Patient Data Registry
Recruiting NCT06058988 - Trastuzumab Deruxtecan (T-DXd) for People With Brain Cancer Phase 2
Not yet recruiting NCT05981170 - Rurality Adapted Physical Activity Sport Health
Not yet recruiting NCT03058809 - Evaluation of Viatarâ„¢ Oncopheresis System in Removing CTC From Whole Blood Phase 1/Phase 2
Completed NCT02529553 - A Study of LY3076226 in Participants With Advanced or Metastatic Cancer Phase 1
Terminated NCT01929941 - An Open-Label Study of a Novel JAK-inhibitor, INCB047986, Given in Patients With Advanced Malignancies Phase 1
Terminated NCT00918645 - Calcium-41 (41Ca) Chloride Aqueous Solution in Diagnosing Patients With Prostate Cancer and Bone Metastasis N/A
Completed NCT01302808 - Romidepsin and Erlotinib Hydrochloride in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer Phase 1
Completed NCT00795678 - Chemotherapeutic Agents in Brain/Breast N/A
Withdrawn NCT00769990 - Genistein in Treating Patients Undergoing External-Beam Radiation Therapy for Bone Metastases Phase 1/Phase 2
Completed NCT00557102 - Cetuximab and Combination Chemotherapy as First-Line Therapy in Treating Patients With Colorectal Cancer That Has Spread to the Liver and/or Lung Phase 2
Recruiting NCT00398437 - Magnetic Resonance Imaging for the Early Detection of CNS Metastases in Women With Stage IV Breast Cancer N/A