Clinical Trials /

Vemurafenib With Lymphodepletion Plus Adoptive Cell Transfer & High Dose IL-2 Metastatic Melanoma

NCT01659151

Description:

The purpose of this study is to find out more about the effects of an investigational combination of medicines, which includes special immune cells (T-cells). A T-cell is a type of lymphocyte, or white blood cell. Lymphocytes are a kind of white blood cell that protect the body from viral infections, help other cells fight bacterial and fungal infections, produce antibodies, fight cancers, and coordinate the activities of other cells in the immune system.

Related Conditions:
  • Melanoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Vemurafenib With Lymphodepletion Plus Adoptive <span class="go-doc-concept go-doc-intervention">Cell Transfer</span> & High Dose IL-2 Metastatic <span class="go-doc-concept go-doc-disease">Melanoma</span>

Title

  • Brief Title: Vemurafenib With Lymphodepletion Plus Adoptive Cell Transfer & High Dose IL-2 Metastatic Melanoma
  • Official Title: A Phase II Clinical Trial of Vemurafenib With Lymphodepletion Plus Adoptive Cell Transfer and High Dose IL-2 in Patients With Metastatic Melanoma
  • Clinical Trial IDs

    NCT ID: NCT01659151

    ORG ID: MCC-16992

    Trial Conditions

    Metastatic Melanoma

    Trial Interventions

    Drug Synonyms Arms
    High Dose Interleukin-2 (IL-2) aldesleukin, Proleukin Combination Therapy
    Vemurafenib Zelboraf, B-Raf enzyme inhibitor Combination Therapy
    Lymphodepletion fludarabine, Fludara, cyclophosphamide, Neostar, Cytoxan Combination Therapy

    Trial Purpose

    The purpose of this study is to find out more about the effects of an investigational
    combination of medicines, which includes special immune cells (T-cells).

    A T-cell is a type of lymphocyte, or white blood cell. Lymphocytes are a kind of white blood
    cell that protect the body from viral infections, help other cells fight bacterial and
    fungal infections, produce antibodies, fight cancers, and coordinate the activities of other
    cells in the immune system.

    Detailed Description

    In this study, these special immune T-cells will be taken from a sample of the participant's
    tumor tissue that will be surgically removed. Certain parts of these cells will be
    multiplied, or grown, in the laboratory. They will then be given back to the patient by an
    infusion in their veins. These cells are called tumor infiltrating lymphocytes (TIL). The
    investigators want to study the benefits and side effects of TIL when they are given with
    the following combination of drugs:

    - Vemurafenib - a type of drug used to slow the growth of certain types of cancer cells.
    This drug will be given for about three weeks while T-cells are being grown in the lab
    and then again after T-cell infusion for up to two years.

    - Fludarabine and cyclophosphamide - two types of chemotherapy drugs. These drugs will be
    used for what is called lymphodepletion. The purpose of lymphodepletion in this study
    is to temporarily reduce the number of normal lymphocytes circulating in the patient's
    body before they are given the T-cells that were grown in the lab. This is so that
    there will be more "space" for the lymphocytes (T-cells) that will be infused in their
    veins.

    - Interleukin-2 (IL-2) - a drug used to help the body's response to treatment on the
    immune system. A high dose regimen of IL-2 will be given after they receive the
    infusion of the T-cells.

    The use of TIL is investigational, meaning it has not been approved by the U.S. Food and
    Drug Administration (FDA). Vemurafenib and IL-2 have been approved by the FDA for the
    treatment of metastatic melanoma and melanoma that cannot be surgically removed. The
    chemotherapy drugs fludarabine and cyclophosphamide, used for lymphodepletion, have been
    approved by the FDA, but not for the treatment of metastatic melanoma.

    The combination of vemurafenib followed by lymphodepletion with chemotherapy, TIL infusion,
    and high dose IL-2 is investigational, and has not been proven to help treat melanoma. This
    combination is not FDA approved; however, the FDA is allowing its use in this study.

    Trial Arms

    Name Type Description Interventions
    Combination Therapy Experimental Combination Chemotherapy and Immunotherapy. The combination of vemurafenib followed by lymphodepletion with chemotherapy, Adoptive Cell Therapy (ACT) with Tumor Infiltrating Lymphocytes (TIL) infusion, and High Dose Interleukin-2 (IL-2). High Dose Interleukin-2 (IL-2), Vemurafenib, Lymphodepletion

    Eligibility Criteria

    Inclusion Criteria:

    - Must have unresectable metastatic stage IV melanoma or stage III intransit or
    regional nodal disease and in the opinion of the PI or treating Coinvestigator is an
    acceptable candidate for adoptive cell transfer (ACT).

    - Residual measurable disease after resection of target lesion(s) for TIL growth

    - Tumor must have a B-RAF V600E, D or K mutation by pyrosequencing, Cobas assay, or
    equivalent (43)

    - Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 - 1. ECOG
    performance status of 0-1 will be inferred if the patient's level of energy is 50%
    of baseline.

    - May be treatment-nave or may have been previously treated for metastatic disease.

    - Women of childbearing potential (WOCBP) must have a negative serum pregnancy test
    within 7 days of starting Vemurafenib.

    - Adequate renal, hepatic and hematologic function, including creatinine of less than
    or equal to 1.7 gm/dL, total bilirubin less than or equal to 2.0 mg/dL, except in
    patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dL,
    aspartic transaminase (AST) and alanine transaminase (ALT) of less than 3X
    institutional upper limit of normal, hemoglobin of 8 gm/dL or more, white blood count
    (WBC) of 3000 per mcL and total granulocytes of 1000 per mcL or more, and platelets
    of 100,000 per mcL or more.

    - Must have a positive screening Epstein-Barr Virus (EBV) antibody titre on screening
    test

    - Patients with antibiotic allergies per se are not excluded; although the production
    of TIL for adoptive transfer includes antibiotics, extensive washing after harvest
    will minimize systemic exposure to antibiotics.

    - At screening, patients with 3 untreated CNS metastases may be included provided
    none of the untreated lesions are > 1 cm in greatest dimension, and there is no
    peri-tumoral edema present on brain imaging (MRI or CT if MRI is contraindicated).

    - At screening, patients with 3 treated central nervous system (CNS) metastases
    treated with either surgical resection and/or radiation therapy may be included.
    Patients may be included if the largest lesion is 1 cm, and there is no evidence of
    progressive CNS disease on brain imaging at least 28 days after treatment.

    - At screening, may be included if the largest lesion is > 1 cm or > 3 in number, and
    there is no evidence of progressive CNS disease on brain imaging at least 90 days
    after treatment with surgery and/or radiation therapy.

    - At screening, must have no known history of congenital long QT syndrome and must have
    a corrected mean QTc interval 450 msec at baseline.

    - No evidence of ongoing cardiac dysrhythmia grade 2, NCI Common Terminology Criteria
    for Adverse Events (CTCAE) v4.0

    - All laboratory and imaging studies must be completed and satisfactory within 30 days
    of signing the consent document, with the exceptions of: negative serum pregnancy
    test for WOCBP must be negative within 7 days of starting Vemurafenib, human
    leukocyte antigen (HLA) typing which will not be repeated if performed previously,
    and pulmonary function tests/cardiac stress tests whose results are valid for 6
    months if performed previously.

    Exclusion Criteria:

    - Patients with active systemic infections requiring intravenous antibiotics,
    coagulation disorders or other major medical illness of the cardiovascular,
    respiratory or immune system, which in the opinion of the principal investigator (PI)
    or treating co-investigator is not acceptable risk for ACT, are excluded.

    - Patients testing positive for HIV titre, Hepatitis B surface antigen, Hepatitis B
    core antibody, Hepatitis C antibody, human T-cell lymphotropic virus type (HTLV) I or
    II antibody, or both rapid plasma reagin (RPR) and fluorescent treponemal antibodies
    (FTA) positive

    - Patients who are pregnant or nursing

    - Patients needing chronic, immunosuppressive systemic steroids are excluded

    - Patients with autoimmune diseases that require immunosuppressive medications

    - Presence of a significant psychiatric disease, which in the opinion of the principal
    investigator or his designee, would prevent adequate informed consent or render
    immunotherapy unsafe or contraindicated

    - Patients with > 3 untreated CNS metastases or evidence of peri-tumoral edema

    - Patients with 3 untreated CNS metastases but with at least one lesion >1 cm or
    peri-tumoral edema

    - Patients with congenital long QT syndrome

    - Patients with invasive malignancy other than melanoma at the time of enrollment and
    within 2 years prior to the first Vemurafenib administration are excluded, except for
    adequately treated (with curative intent) basal or squamous cell carcinoma of the
    skin, in situ carcinoma of the cervix, in situ ductal adenocarcinoma of the breast,
    in situ prostate cancer, or limited stage bladder cancer or other cancers from which
    the patient has been disease-free for at least 2 years.

    - Unable to swallow pills

    - Patients with treated CNS metastases > 1 cm or > 3 in number will be excluded if
    there is evidence of progressive CNS disease on brain imaging at least 90 days after
    treatment with surgery and/or radiation therapy.

    - Unable to comprehend and give informed consent

    - Previous BRAF inhibitor treatment

    - Male patients with female partners of childbearing potential who do not agree to use
    2 FDA-accepted forms of contraception during sexual intercourse with women of
    child-bearing potential from the start of Vemurafenib and up to at least 6 months
    after discontinuing Vemurafenib

    - WOCBP who do not agree to use 2 FDA forms of contraception during sexual intercourse
    from the start of Vemurafenib and up to at least 6 months after discontinuing
    Vemurafenib

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Overall Response (OR)

    Drop Out Rate

    Secondary Outcome Measures

    Number of Participants with Progression Free Survival (PFS)

    Trial Keywords

    metastatic

    melanoma

    cell transfer

    ACT

    T-cell

    immunotherapy

    antibodies

    lymphocytes