Clinical Trial 18959

Cancer Type: Gynecological Tumor
Interventions:Fluconazole; IL-2 (Interleukin-2); LN-145; MESNA; Neupogen (filgrastim); cyclophosphamide; cytoxan (cyclophosphamide); filgrastim; fludarabine (Fludarabine phosphate)

Study Type: Treatment
Phase of Study: Phase II
Investigators:

  • Robert Wenham

Overview

Study Title

A Phase 2 Study to Evaluate the Safety, Tolerability and Efficacy of Cell Transfer Therapy Using Autologous Tumor Infiltrating Lymphocytes (LN-145) followed by IL-2 in Patients with Recurrent and/or Metastatic Cervical Carcinoma

Summary

The purpose of this study is to find out if an investigational product called LN-145 is safe to give to participants with recurrent and/or metastatic cervical cancer and if processing tumors to obtain cells in a central lab works. LN-145 is also called tumor infiltrating lymphocytes (TILs). TILs are generated by processing the patient¿s own tumor in a lab to extract and grow specialized white cells called lymphocytes that may attack their tumor. LN-145 is an investigational drug. Investigational means that it has not been approved by the Food and Drug Administration (FDA). Other drugs used in this study although they may be approved for other conditions may be considered investigational in this study.

Objective

Primary Objectives: - To evaluate the safety and tolerability of lymphodepletion, LN-145, and IL-2 in patients with recurrent and/or metastatic cervical carcinoma. - To evaluate the efficacy of therapy using the overall response rate (ORR) in patients with recurrent and/or metastatic cervical carcinoma. Secondary Objectives: - To evaluate other efficacy parameters such as complete response (CR) rate, the duration of response (DOR), progression-free survival (PFS), and overall survival (OS) in patients with recurrent and/or metastatic cervical carcinoma. Exploratory Objectives: - To explore persistence of TILs and immune correlates of response, survival, toxicity of the treatment.

Inclusion Criteria

  • Must be greater than 18 years of age at the time of consent.
  • Must have metastatic, recurrent or persistent squamous cell carcinoma, adenosquamous carcinoma or adenocarcinoma of the cervix, which is not amenable to curative treatment with surgery and/or radiation therapy.
  • Must have had at least 1 prior systemic immunotherapy or chemotherapeutic treatment for cervical carcinoma. Patients must have either progressive disease or no response (i.e., no PR or CR) while receiving or after the completion of the most recent prior treatment.
  • Any prior therapy directed at the malignant tumor, including radiation therapy, chemotherapy, biologic/targeted agents and immunologic agents must be discontinued at least 28 days prior to tumor resection.
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Must be seronegative for the HIV antibody, hepatitis B antigen, and hepatitis C antibody or antigen.
  • Potential participants of childbearing potential must be willing to practice an approved method of birth control starting at the time of informed consent and for 1 year after the completion of the study treatment regimen.

  • Exclusion Criteria

  • Have received prior cell transfer therapy, which includes non-myeloablative or myeloablative chemotherapy regimen.
  • Are on a systemic steroid therapy (greater than 10 mg of prednisone or equivalent daily).
  • Currently have prior therapy-related toxicities greater than Grade 1 according to NCI-CTCAE v4.03; except for peripheral neuropathy, alopecia or vitiligo prior to enrollment/resection.
  • Documented Grade 2 or greater diarrhea or colitis as a result of previous immunotherapy within 6 months from screening.
  • History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, IL-2, or aminoglycosides (e.g., gentamicin or streptomycin).
  • Active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system.
  • A symptomatic and/or untreated brain metastases (of any size and any number).
  • Have any form of primary immunodeficiency, such as severe combined immunodeficiency disease or acquired immune deficiency syndrome (AIDS).
  • Diagnosis of end-stage renal disorder requiring hemodialysis.
  • Have a left ventricular ejection fraction (LVEF) less than 45%.
  • Have a FEV1 (forced expiratory volume in one second) of less than or equal to 60% of normal.