Clinical Trials /

Transfer of Genetically Engineered Lymphocytes in Melanoma Patients

NCT01586403

Description:

This is a phase one trial to determine if genetically engineered lymphocytes can be safely delivered to patients with metastatic melanoma.

Related Conditions:
  • Melanoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Transfer of Genetically Engineered Lymphocytes in <span class="go-doc-concept go-doc-disease">Melanoma</span> Patients

Title

  • Brief Title: Transfer of Genetically Engineered Lymphocytes in Melanoma Patients
  • Official Title: Transfer of Genetically Engineered Lymphocytes in Melanoma Patients: A Phase 1 Dose Escalation Study
  • Clinical Trial IDs

    NCT ID: NCT01586403

    ORG ID: 203732

    NCI ID: R44CA126461

    Trial Conditions

    Melanoma

    Trial Interventions

    Drug Synonyms Arms

    Trial Purpose

    This is a phase one trial to determine if genetically engineered lymphocytes can be safely
    delivered to patients with metastatic melanoma.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Dose 1 Experimental Subjects in cohort 1 will receive 2.5 x 106 TIL 1383I TCR transduced T cells per kg body weight
    Dose 2 Experimental cohort 2 will receive 7.5 x 106 TIL 1383I TCR transduced T cells per kg body weight.
    Dose 3 Experimental Subjects in cohort 3 will receive 2.5 x 107 TIL 1383I TCR transduced T cells per kg body weight.
    Dose 4 Experimental Subjects will then receive a single infusion of autologous bulk TIL 1383I TCR transduced T cells supported with low dose IL-2. Autologous bulk TIL 1383I TCR transduced T cells means the infusion will consist of a polyclonal mixture of CD4+ and CD8+ T cells expressing the TIL 1383I TCR. Subjects in cohort 4 will receive 7.5 x 107 TIL 1383I TCR transduced T cells per kg body weight.

    Eligibility Criteria

    Inclusion Criteria:

    - Patients must have a diagnosis of metastatic melanoma which is measurable either
    clinically or radiologically.

    - Patients must be 18 years of age or older.

    - Patients must consent to be in the study and must have signed and dated an approved
    consent form, which conforms to federal and institutional guidelines.

    - Patients must have a performance status of 0 or 1 ECOG PS scale (see Appendix B).

    - The ability to provide written informed consent prior to study specific screening
    procedures, with the understanding that the patient has the right to withdraw from
    the study at any time.

    - Patients' melanoma must be positive for both tyrosinase and HLA-A2 per Loyola
    University Medical Center pathologic review from FNA/core/excisional biopsy of
    lesion.

    - Cardiac ejection fraction >50% as determined by screening echocardiogram.

    - Patients that have undergone treatment with anti-CTLA-4 (Cytotoxic T-Lymphocyte
    Antigen 4) antibody must have at least 3 months from last dose of CTLA-4 antibody
    before they can be enrolled into this study.

    - The patients BRAF mutation status at position 600 must be known prior to enrollment.
    Patients with V600E mutations are eligible if they have failed Vemurafenib therapy or
    have been offered Vemurafenib therapy and refused.

    - Patients treated with prior Interleukin-2 will be allowed to be in this study.

    Exclusion Criteria:

    - Special classes of subjects such as fetuses, pregnant women, children, prisoners,
    institutionalized individuals, or others who are likely to be vulnerable.

    - ECOG performance status of 2 or greater.

    - Patients with a history metastatic melanoma involving the brain will be excluded if
    they have active disease or have had active disease within the prior six months that
    was not controlled with surgery or radiotherapy.

    - Patients taking steroids for disease control or pain management

    - Patients must not be pregnant or nursing because of the potentially harmful effects
    of these agents on a developing fetus. Women/men of reproductive potential must have
    agreed to use an effective contraceptive method.

    - Patients whose BRAF V600E mutation status is unknown, have the BRAF V600E mutation
    and are responding to Vemurafenib therapy, or have the BRAF V600E mutation and have
    not been offered the option of receiving Vemurafenib therapy for the treatment of
    their melanoma.

    - No other prior malignancy is allowed except for the following: adequately treated
    basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
    Stage I or II cancer from which the patient is currently in complete remission, or
    any other cancer from which the patient has been disease-free for five years.

    - Patients that have undergone Tyrosinase immunotherapy.

    - Patients that have undergone immunotherapy in combination with non-myeloablative
    chemotherapy.

    - Any of the following abnormal laboratory values:

    - Absolute neutrophil count less than 1.5 x 109/L

    - Platelet count less than 100 x 109/L

    - Serum bilirubin greater than 1.5 x upper limit of normal (ULN)

    - Serum ALT, AST greater than 2.5 x ULN

    - Serum ALP greater than 2 x ULN

    - Serum Albumin less than 2.5 g/dL

    - International Normalized Ratio (INR) greater than 1.5

    - Serum creatinine calculated creatinine clearance by the method of Cockcroft and
    Gault (less than 50mL/min).

    - Patients should not have any evidence of active or uncontrolled infection requiring
    treatment with antibiotics.

    - Any severe or poorly controlled systemic disease (e.g., hypertension; clinically
    significant cardiovascular, pulmonary, or metabolic disease, disorders of
    wound-healing, ulcer or bone fracture).

    - Patients who have received any chemotherapy or investigational treatment within 4
    weeks of study start.

    - Known infection with HIV, HBV, or HCV.

    - Known hypersensitivity to any of the components of the study drugs.

    - Patients assessed by the investigator to be unable or unwilling to comply with the
    requirements of the protocol.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Find dose of autologous T cell receptor

    Secondary Outcome Measures

    Trial Keywords

    Melanoma

    Gene Therapy

    Adoptive T-Cell Transfer

    IL-2