Vemurafenib and White Blood Cell Therapy for Advanced Melanoma

Melanoma Clinical Trial

Official title: A Pilot Trial of the Combination of Vemurafenib With Adoptive Cell Therapy in Patients With Metastatic Melanoma

Status Terminated

Clinical Trial Summary

Background:

• One possible treatment for advanced melanoma involves collecting white blood cells from the person with cancer and growing them in a laboratory. The cells can then be given back to the donor. This study will use this white blood cell treatment with the cancer treatment drug vemurafenib. Vemurafenib targets melanoma cells that have a mutation in the B-raf gene, and may be able to make them shrink.

Objectives:

• To see if vemurafenib and white blood cell therapy is a safe and effective treatment for advanced melanoma.

Eligibility:

• Individuals at least 18 years and less than or equal to 66 years of age who have advanced melanoma that contains the B-raf genetic mutation.

Design:

• Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected.

• White blood cells will be collected from tumor cells. These cells will be collected during surgery or a tumor biopsy.

• Participants will have leukapheresis to collect additional white blood cells for the procedure.

• Participants will take vemurafenib twice a day, starting 3 weeks before receiving the white blood cells.

• Participants will have 1 week of chemotherapy to prepare their immune system to accept the white blood cells.

• Participants will receive an infusion of their collected white blood cells. They will also receive aldesleukin for up to 5 days to boost the immune system s response to the white blood cells. They will remain in the hospital until they have recovered from the treatment.

• Participants will have frequent follow-up visits to monitor the outcome of the treatment.

Clinical Trial Description

Background:

Adoptive cell therapy (ACT) with tumor infiltrating lymphocytes (TIL) can mediate the regression of bulky metastatic melanoma when administered to the autologous patient along with high-dose aldesleukin (IL-2) following a non-myeloablative lymphodepleting chemotherapy preparative regimen.

Vemurafenib (VEM) administration has been shown to mediate objective responses in 50-60 percent of patients with metastatic melanoma bearing a BRAF mutation though many of these responses are transient.

There are several reasons to suggest that the combination of ACT with VEM will synergize in the destruction of melanoma including 1) rapid tumor destruction by VEM may provide a vaccine-like stimulus to the transferred TIL; 2) VEM has been shown to upregulate the expression of melanoma antigens; 3)VEM may make residual melanoma cells more sensitive to immune damage.

Objectives:

The primary objective is to determine the safety of the administration of vemurafenib in conjunction with ACT consisting of autologous TIL infused along with high dose aldesleukin following a non-myeloablative lymphodepleting preparative regimen.

The secondary objectives are:

• To gain preliminary information concerning the ability of the combination therapy to mediate clinical tumor regression in patients with metastatic melanoma.

• To study the immunologic impact of VEM administration on the lymphoid infiltrate in melanoma deposits.

Eligibility:

Patients greater than or equal to 18 years old with pathologically confirmed diagnosis of

metastatic melanoma that expresses the VtoE BRAF mutation and VtoK BRAF mutation.

Patients with measurable disease, absolute neutrophil count greater than 1000/mm(3) and platelet count greater than 100,000/mm(3).

No serious comorbid conditions such as active systemic infections, coagulation disorders, or other active major medical illnesses of the cardiovascular, respiratory or immune systems.

Design:

Patients will undergo biopsy or resection to obtain tumor for generation of autologous TIL cultures.

When cryopreserved TIL are available patients will begin the administration of VEM 960 mg (day 1) twice daily until disease progression or patients are taken off protocol.

On day -7, patients will begin a non-myeloablative lymphocyte depleting preparative regimen of cyclophosphamide (60 mg/kg/day IV) on days -7 and -6 and fludarabine (25 mg/m2/day IV) on days -5 through -1.

On day 0, patients will receive between 1x109 to 2x1011 young TIL and then begin high dose aldesleukin (720,000 IU/kg IV every 8 hours for up to 15 doses).

Clinical and immunologic responses will be evaluated about 4-6 weeks after the last dose of aldesleukin.

This pilot trial will accrue 25 patients. ;

Related Conditions & MeSH terms

• Melanoma
• Metastatic Cancer

• NCT number: NCT01585415
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Terminated
• Phase: Phase 1
• Start date: April 9, 2012
• Completion date: July 21, 2016