Genetically Engineered T Cells and Low-Dose Aldesleukin After Combination Chemotherapy in Treating Patients With Metastatic Melanoma

Status: Active

Description

This phase I trial studies the side effects and best dose of genetically engineered T cells when given together with low-dose aldesleukin after combination chemotherapy in treating patients with metastatic melanoma. Placing a gene that has been created in the laboratory into white blood cells may make the body build an immune response to kill tumor cells. Aldesleukin may stimulate the white blood cells to kill melanoma cells. Drugs used in chemotherapy, such as fludarabine phosphate and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving genetically engineered T cells and aldesleukin after combination chemotherapy may be an effective treatment for melanoma.

Eligibility Criteria

Inclusion Criteria

  • Patients must have a diagnosis of metastatic melanoma which is measurable either clinically or radiologically
  • 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 Eastern Cooperative Oncology Group (ECOG) performance status (PS) scale
  • 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 human leukocyte antigen (HLA)-A2 per Loyola University Medical Center pathologic review from fine needle aspiration (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 an approved BRAF inhibitor or MEK inhibitor therapy or have been offered an approved BRAF inhibitor or MEK inhibitor 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 a BRAF inhibitor or MEK inhibitor therapy, or have the BRAF V600E mutation and have not been offered the option of receiving a BRAF inhibitor or MEK inhibitor 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
  • Absolute neutrophil count < 1.5 x 10^9/L
  • Platelet count < 100 x 10^9/L
  • Serum bilirubin > 1.5 x upper limit of normal (ULN)
  • Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) > 2.5 x ULN
  • Serum alkaline phosphatase (ALP) > 2 x ULN
  • Serum Albumin < 2.5 g/dL
  • International Normalized Ratio (INR) > 1.5
  • Serum creatinine calculated creatinine clearance by the method of Cockcroft and Gault (< 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 human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (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

Locations & Contacts

Illinois

Maywood
Loyola University Medical Center
Status: Active
Contact: Joseph I. Clark
Phone: 708-327-3236
Email: jclark@lumc.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To establish the recommended phase two dose of autologous T cell receptor transduced T cells when administered with low dose interleukin (IL)-2 (aldesleukin) to stage IV melanoma patients following a nonmyeloablative and lymphodepleting chemotherapy preparative regimen.

SECONDARY OBJECTIVES:

I. To evaluate biologic and immunologic parameters associated with the adoptively transferred T cell receptor transduced T cells, including auditory and visual changes.

II. To determine if systemic infusion of T cell receptor gene modified autologous T cells can mediate objective clinical responses in stage IV melanoma patients.

OUTLINE: This is a dose-escalation study of TIL 1383I TCR transduced autologous T cells.

Patients receive fludarabine phosphate intravenously (IV) over 15-30 minutes on days -5 to -1 and cyclophosphamide IV on days -3 to -2. Patients then receive TIL 1383I TCR transduced autologous T cells IV over 30 minutes on day 0 followed by low-dose aldesleukin IV over 15 minutes three times daily (TID) for 7 days.

After completion of study treatment, patients are followed up once weekly for 6 weeks and then at 3, 6, and 12 months.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
Loyola University Medical Center

Principal Investigator
Joseph I. Clark

Trial IDs

Primary ID LU# 203732
Secondary IDs 9358, NCI-2012-02875, P01CA154778, 203732, 203732092111, R44CA126461
Clinicaltrials.gov ID NCT01586403