Vemurafenib and White Blood Cell Therapy for Advanced Melanoma

NCT01585415 | Terminated Phase 1

• 2 other identifiers: 12011412-C-0114
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Metastatic Cancer; Melanoma

Keywords

Tumor Infiltrating Lymphocytes; Immunotherapy; Adoptive Cell Therapy; B Raf Inhibitor

Outcome Measures

Primary Outcomes (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.

  approximately 1 year

Study Arms (1)

Single Arm

EXPERIMENTAL

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; Biological: Young TIL; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Aldesleukin

Interventions

Vemurafenib DRUG

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.

Single Arm

Young TIL BIOLOGICAL

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.

Single Arm

Cyclophosphamide DRUG

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.

Single Arm

Fludarabine DRUG

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

Single Arm

Aldesleukin DRUG

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)

Single Arm

Eligibility Criteria

• Age: 18 Years - 66 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Measurable metastatic melanoma that expresses the VtoE BRAF mutation and VtoK BRAF mutation assessed in a CLIA certified laboratory.
• 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.
• Greater than or equal to 18 and less than or equal to 66 years of age.
• 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.
• Life expectancy of greater than three months
• Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus.
• Willing to sign a durable power of attorney.
• Able to understand and sign the Informed Consent Document
• Clinical performance status of ECOG 0 or 1.
• Hematology:
• Absolute neutrophil count greater than 1000/mm(3)
• Hemoglobin greater than 8.0 g/dl
• Platelet count greater than 100,000/mm(3)
• 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.)

You may not qualify if:

• Prior cell transfer therapy which included a myeloablative chemotherapy regimen (i.e. 1200 TBI or 200 TBI plus chemotherapy).
• Previous treatment with Vemurafenib.
• Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.
• Systemic steroid therapy requirement.
• 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.
• Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and AIDS).
• 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.)
• History of severe immediate hypersensitivity reaction to any of the agents used in this study.
• History of coronary revascularization or ischemic symptoms.
• Any patient known to have an LVEF less than or equal to 45 percent.
• In patients \> 60 years old, documented LVEF of less than or equal to 45 percent.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Boni A, Cogdill AP, Dang P, Udayakumar D, Njauw CN, Sloss CM, Ferrone CR, Flaherty KT, Lawrence DP, Fisher DE, Tsao H, Wargo JA. Selective BRAFV600E inhibition enhances T-cell recognition of melanoma without affecting lymphocyte function. Cancer Res. 2010 Jul 1;70(13):5213-9. doi: 10.1158/0008-5472.CAN-10-0118. Epub 2010 Jun 15.

  PMID: 20551059 BACKGROUND

• Dudley ME, Yang JC, Sherry R, Hughes MS, Royal R, Kammula U, Robbins PF, Huang J, Citrin DE, Leitman SF, Wunderlich J, Restifo NP, Thomasian A, Downey SG, Smith FO, Klapper J, Morton K, Laurencot C, White DE, Rosenberg SA. Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J Clin Oncol. 2008 Nov 10;26(32):5233-9. doi: 10.1200/JCO.2008.16.5449. Epub 2008 Sep 22.

  PMID: 18809613 BACKGROUND

• Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, Dummer R, Garbe C, Testori A, Maio M, Hogg D, Lorigan P, Lebbe C, Jouary T, Schadendorf D, Ribas A, O'Day SJ, Sosman JA, Kirkwood JM, Eggermont AM, Dreno B, Nolop K, Li J, Nelson B, Hou J, Lee RJ, Flaherty KT, McArthur GA; BRIM-3 Study Group. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011 Jun 30;364(26):2507-16. doi: 10.1056/NEJMoa1103782. Epub 2011 Jun 5.

  PMID: 21639808 BACKGROUND

MeSH Terms

Conditions

Neoplasm Metastasis; Melanoma

Interventions

Vemurafenib; Cyclophosphamide; fludarabine; aldesleukin

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds

Study Officials

• Steven A Rosenberg, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2012
• First Posted: April 25, 2012
• Study Start: April 9, 2012
• Primary Completion: July 21, 2016
• Study Completion: July 21, 2016
• Last Updated: November 21, 2019

Record last verified: 2016-07-21

Locations

US (1)