Vemurafenib and White Blood Cell Therapy for Advanced Melanoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01585415
First received: April 24, 2012
Last updated: July 31, 2014
Last verified: December 2013
  Purpose

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.

Condition Intervention Phase
Metastatic Cancer
Melanoma
Drug: Vemurafenib
Drug: Young TIL
Drug: Cyclophosphamide
Drug: Fludarabine
Drug: Aldesleukin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Trial of the Combination of Vemurafenib With Adoptive Cell Therapy in Patients With Metastatic Melanoma

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • 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.

Secondary Outcome Measures:
  • Gain preliminary information concerning the ability of combination therapy to mediate clinical tumor regression patients with metastatic melanoma.
  • Study the immunologic impact of VEM administration on the lymphoid infiltrate in melanoma deposits.

Estimated Enrollment: 26
Study Start Date: April 2012
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Vemurafenib
    N/A
    Drug: Young TIL
    N/A
    Drug: Cyclophosphamide
    N/A
    Drug: Fludarabine
    N/A
    Drug: Aldesleukin
    N/A
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 66 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

-INCLUSION CRITERIA:

  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 years and less htan or equal to 66 years of age.
  4. Willing to practice birth control during treatment and for four months after receiving all protocol related therapy.
  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 recieves 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.

EXCLUSION CRITERIA:

  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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01585415

Contacts
Contact: Linda Williams, R.N. (866) 820-4505 linda_williams@nih.gov
Contact: Steven A Rosenberg, M.D. (301) 496-4164 sar@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact NCI/Surgery Branch Recruitment Center    866-820-4505    ncisbirc@mail.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Steven A Rosenberg, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT01585415     History of Changes
Other Study ID Numbers: 120114, 12-C-0114
Study First Received: April 24, 2012
Last Updated: July 31, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Immunotherapy
Adoptive Cell Therapy
B Raf Inhibitor

Additional relevant MeSH terms:
Melanoma
Neoplasm Metastasis
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplastic Processes
Pathologic Processes
Cyclophosphamide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on September 18, 2014