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Vemurafenib and White Blood Cell Therapy for Advanced Melanoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01585415
Recruitment Status : Terminated
First Posted : April 25, 2012
Last Update Posted : November 21, 2019
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:


- 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.


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


- 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.


  • 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.

Condition or disease Intervention/treatment Phase
Metastatic Cancer Melanoma Drug: Vemurafenib Biological: Young TIL Drug: Cyclophosphamide Drug: Fludarabine Drug: Aldesleukin Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Trial of the Combination of Vemurafenib With Adoptive Cell Therapy in Patients With Metastatic Melanoma
Study Start Date : April 9, 2012
Actual Primary Completion Date : July 21, 2016
Actual Study Completion Date : July 21, 2016

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma
Drug Information available for: Vemurafenib

Arm Intervention/treatment
Experimental: Single Arm
Two weeks prior to the start of the preparative regimen, patients will begin taking vemurafenib. Patients will then receive lymphocyte depleting preparative regimen of cyclophosphamide and fludarabine, followed by young TIL and high dose aldesleukin
Drug: Vemurafenib
Vemurafenib will administered orally twice a day at a dose of 960 mg from day -21 (+/- 7 days)until disease progression or patients are taken off protocol.

Biological: Young TIL
Young TIL will be administered intravenously on day 0(1x10e9 to 2x10e11) in the Patient Care Unit over 20-30 minutes via non-filtered tubing, gently agitating the bag during infusion to prevent cell clumping.

Drug: Cyclophosphamide
Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W with Mesna 15 mg/kg/day X 2 days over 1 hr.

Drug: Fludarabine
Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.

Drug: Aldesleukin
Aldeskeukin 720,000 IU/kg IV (based on total body weight)over 15 minutes every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses)

Primary Outcome Measures :
  1. 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. [ Time Frame: approximately 1 year ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 66 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  1. Measurable metastatic melanoma that expresses the VtoE BRAF mutation and VtoK BRAF mutation assessed in a CLIA certified laboratory.
  2. Patients with 3 or less brain metastases that are less than 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible. Patients with surgically resected brain metastases are eligible.
  3. Greater than or equal to 18 and less than or equal to 66 years of age.
  4. Patients of both genders must be willing to practice birth control from the time of enrollment on the study and for four months after treatment.
  5. Life expectancy of greater than three months
  6. Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus.
  7. Willing to sign a durable power of attorney.
  8. Able to understand and sign the Informed Consent Document
  9. Clinical performance status of ECOG 0 or 1.
  10. Hematology:

    • Absolute neutrophil count greater than 1000/mm(3)
    • Hemoglobin greater than 8.0 g/dl
    • Platelet count greater than 100,000/mm(3)
  11. Serology:

    • Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)
    • Seronegative for hepatitis B antigen, or hepatitis C antibody or antigen.
  12. Chemistry:

    • Serum ALT/AST less than three times the upper limit of normal.
    • Calculated creatinine clearance (eGFR) > 50 ml/min.
    • Total bilirubin less than or equal to 2 mg/dl, except in patients with Gilbert s Syndrome who must have a total bilirubin less than 3 mg/dl.
  13. More than four weeks must have elapsed since any prior systemic therapy at the time of treatment, and patients toxicities must have recovered to a grade 1 or less (except for alopecia or vitiligo). Patients must have stable or progressing disease after prior treatment.

    Note: Patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less or as specified in the eligibility criteria in Section 2.1.1.

  14. Six weeks must have elapsed from the time of any antibody therapy that could affect an anti cancer immune response, including anti-CTLA4 antibody therapy at the time the patient receives the preparative regimen to allow antibody levels to decline.

    Note: Patients who have previously received ipilimumab and have documented GI toxicity must have a normal colonoscopy with normal colonic biopsies.

  15. EKG with mean QTc interval < 450 msec.


  1. Prior cell transfer therapy which included a myeloablative chemotherapy regimen (i.e. 1200 TBI or 200 TBI plus chemotherapy).
  2. Previous treatment with Vemurafenib.
  3. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.
  4. Systemic steroid therapy requirement.
  5. Active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, as evidenced by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
  6. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and AIDS).
  7. Opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities.)
  8. History of severe immediate hypersensitivity reaction to any of the agents used in this study.
  9. History of coronary revascularization or ischemic symptoms.
  10. Any patient known to have an LVEF less than or equal to 45 percent.
  11. In patients > 60 years old, documented LVEF of less than or equal to 45 percent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01585415

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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)
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Principal Investigator: Steven A Rosenberg, M.D. National Cancer Institute (NCI)
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Responsible Party: National Cancer Institute (NCI) Identifier: NCT01585415    
Other Study ID Numbers: 120114
First Posted: April 25, 2012    Key Record Dates
Last Update Posted: November 21, 2019
Last Verified: July 21, 2016
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Tumor Infiltrating Lymphocytes
Adoptive Cell Therapy
B Raf Inhibitor
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Protein Kinase Inhibitors
Enzyme Inhibitors