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Protocol Details

A Pilot Trial of the Combination of Vemurafenib with Adoptive Cell Therapy in Patients with Metastatic Melanoma

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

12-C-0114

Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18
Max Age: 66

Referral Letter Required

No

Population Exclusion(s)

Children

Special Instructions

Currently Not Provided

Keywords

Immunotherapy;
Adoptive Cell Therapy;
B Raf Inhibitor

Recruitment Keyword(s)

None

Condition(s)

Metastatic Cancer;
Melanoma

Investigational Drug(s)

Young TIL

Investigational Device(s)

None

Intervention(s)

Drug: Vemurafenib
Drug: Young TIL
Drug: Cyclophosphamide
Drug: Fludarabine
Drug: Aldesleukin

Supporting Site

National Cancer Institute

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.

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Eligibility

INCLUSION CRITERIA:

a.Measurable metastatic melanoma that expresses the VtoE BRAF mutation and VtoK BRAF mutation assessed in a CLIA certified laboratory.

b. 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.

c. Greater than or equal to 18 years and less htan or equal to 66 years of age.

d. Willing to practice birth control during treatment and for four months after receiving all protocol related therapy.

e. Life expectancy of greater than three months

f. Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus.

g. Willing to sign a durable power of attorney.

h. Able to understand and sign the Informed Consent Document

i. Clinical performance status of ECOG 0 or 1.

j. Hematology:

- Absolute neutrophil count greater than 1000/mm(3)

- Hemoglobin greater than 8.0 g/dl

- Platelet count greater than 100,000/mm(3)

k. 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.

l. 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.

m. 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.

n. 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.

o. EKG with mean QTc interval < 450 msec.

EXCLUSION CRITERIA:

a. Prior cell transfer therapy which included a myeloablative chemotherapy regimen (i.e. 1200 TBI or 200 TBI plus chemotherapy).

b. Previous treatment with Vemurafenib.

c. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.

d. Systemic steroid therapy requirement.

e. 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.

f. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and AIDS).

g. 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.)

h. History of severe immediate hypersensitivity reaction to any of the agents used in this study.

i. History of coronary revascularization or ischemic symptoms.

j. Any patient known to have an LVEF less than or equal to 45 percent.

k. In patients > 60 years old, documented LVEF of less than or equal to 45 percent.


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Citations:

Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66.

Atkins MB, Kunkel L, Sznol M, Rosenberg SA. High-dose recombinant interleukin-2 therapy in patients with metastatic melanoma: long-term survival update. Cancer J Sci Am. 2000 Feb;6 Suppl 1:S11-4.

Gogas HJ, Kirkwood JM, Sondak VK. Chemotherapy for metastatic melanoma: time for a change? Cancer. 2007 Feb 1;109(3):455-64.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Steven A. Rosenberg, M.D.
National Cancer Institute (NCI)
BG 10-CRC RM 3-3940
10 CENTER DR
BETHESDA MD 20814
(301) 496-4164
sar@mail.nih.gov

Linda Williams, R.N.
National Cancer Institute (NCI)
National Institutes of Health
Building 10
Room 2B06
10 Center Drive
Bethesda, Maryland 20892
(866) 820-4505
linda_williams@nih.gov

Recruitment Center - SB
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Building 10, Room 2-1730, Bethesda, Maryland 20892, United States
(866) 820-4505
ncisbirc@mail.nih.gov

Clinical Trials Number:

NCT01585415

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