Adoptive Tumor-infiltrating Lymphocyte Transfer With Nivolumab for Melanoma

Study Purpose

This study is to investigate safety and feasibility of a combination therapy of a tumor infiltrating lymphocytes (TIL) transfer with anti-programmed cell death protein (PD)-1 therapy in patients with metastatic melanoma that failed immunotherapy.Tumor-infiltrating lymphocytes will be expanded from resected melanoma samples from the patient and expanded TILs will be transferred to the patient after non-myeloablative chemotherapy with cyclophosphamide and fludarabine. TIL transfer will be combined with low dose Interleukin (IL)-2 and nivolumab anti-PD-1 treatment. The study uses a personalized Investigational Medicinal Product (IMP), i.e. TIL product and in combination with IL-2 treatment and nivolumab.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years - 75 Years
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Histologically confirmed unresectable or metastatic melanoma - At least 1 PD-1 targeted immunotherapy and BRAF inhibition in case of BRAF mutated melanoma - Resectable tumor mass and measurable disease by CT or MRI per RECIST 1.1 criteria (in addition to the resected lesion) - World Health Organization (WHO) clinical performance Status (ECOG) 0-1 - Adequate organ function - Patients of both genders must be willing to practice a highly effective method of birth control during treatment and for five months after receiving the last dose of nivolumab for women and seven months for men - Patients must be able to understand and sign the Informed consent document - Hematology: Absolute neutrophil count greater than 1.5 x 109/L without support of filgrastim.
Platelet count greater than 100 x 109/L. Hemoglobin greater than 5 mmol/L, or 80 g/L.
  • - Chemistry: Serum alanine aminotransferase (ALAT)/ aspartate transaminase (ASAT) less than 3 times the upper limit of normal, unless patients have liver metastases (< 5 times ULN).
Serum creatinine clearance 50 ml/min or higher. Total Bilirubin less than or equal to 20 micromol/L, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 50 micromol/L. Lactate dehydrogenase (LDH) ≤ 2x ULN
  • - Serology: Seronegative for HIV antibody.
Seronegative for hepatitis B antigen, and hepatitis C antibody. Seronegative for syphilis.

Exclusion Criteria:

  • - Life expectancy of less than three months - Patients with metastatic ocular/ mucosal or other non-cutaneous melanoma.
  • - Requirement for immunosuppressive doses of systemic corticosteroids (>10 mg/day prednisone or equivalent) or other immunosuppressive drugs within the last 3 weeks prior to randomization - Uncontrolled central nervous system (CNS) metastases.
Controlled CNS metastases must be for at least 4 weeks stable.
  • - Documented Forced expiratory volume at one second (FEV1) less than or equal to 50% predicted for patients with: - A prolonged history of cigarette smoking (greater than 20 pack/year within the past 2 years) - Symptoms of respiratory distress - All patients' toxicities due to prior non-systemic treatment must have recovered to a grade 1 or less.
Patients may have undergone minor surgical procedures or focal palliative radiotherapy (to non-target lesions) within the past 4 weeks, as long as all toxicities have recovered to grade 1 or less.
  • - Women who are pregnant or breastfeeding, because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
  • - Any active systemic infections, coagulation disorders or other active major medical illnesses.
  • - Contraindication for IL-2 or nivolumab (allergies etc.).
  • - Any autoimmune disease: patients with a documented history of inflammatory bowel disease, including ulcerative colitis and Crohn's disease are excluded from this study as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, autoimmune thyroiditis (e.g. Hashimoto's disease), autoimmune hepatitis, systemic progressive sclerosis (scleroderma), Systemic Lupus Erythematosus, autoimmune vasculitis (e.g., Wegener's Granulomatosis).
Subjects with motor neuropathy considered of autoimmune origin (e.g., Guillain-Barré Syndrome) are excluded from this study. Patients with vitiligo are eligible to enter the study

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04165967
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

University Hospital, Basel, Switzerland
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Heinz Läubli, MD PhDAlfred Zippelius, Prof.
Principal Investigator Affiliation Division of Medical Oncology and Cancer Immunology, University Hospital BaselDivision of Medical Oncology and Cancer Immunology, University Hospital Basel
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

OtherOther
Overall Status Recruiting
Countries Switzerland
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Advanced Melanoma
Additional Details

Adoptive cell therapy has been previously shown to be an effective treatment option for patients with melanoma. Due to an immunosuppressive microenvironment, not all patients respond to this therapy. In this trial, the immune suppressive microenvironment will be targeted by adding a PD-1 blocking antibody in combination with a TIL Transfer. Tumor-infiltrating lymphocytes will be expanded from resected melanoma samples from the patient and expanded TILs will be transferred to the patient after non-myeloablative chemotherapy with cyclophosphamide and fludarabine. TIL transfer will be combined with low dose IL-2 and nivolumab anti-PD-1 treatment. The study uses a personalized IMP, i.e. TIL product and in combination with IL-2 treatment and nivolumab.

Arms & Interventions

Arms

Experimental: Tumor-infiltrating lymphocyte product (TIL) transfer

The TIL product will be produced from excised tumor lesions from the patient. Expanded TILs will be transferred to the patient after non-myeloablative chemotherapy with cyclophosphamide and fludarabine. TIL transfer will be combined with low dose IL-2 and nivolumab anti-PD-1 treatment. The transplant product will be produced in the Good Manufacturing Practice (GMP) facility of the University Hospital in Basel. TIL transfer to Patient at Day 0.

Interventions

Drug: - Combination of TIL Transfer with anti-PD-1 Therapy and low dose IL-2

The study uses a personalized IMP, i.e. TIL product and in combination with IL-2 treatment and nivolumab. Day 0: Autologous TIL: (minimum 5 x 109 and up to a maximum of 2 x 1011 lymphocytes) administered intravenously over 20 to 30 minutes. Day 0: Interleukin-2 (Proleukin): 125.000 IU/kg/day s.c. for maximum 12 days as inpatients with a 2 days break after the first 4-5 doses (maximum 10 days dosing). Actual body weight will be used in calculating the dose of interleukin-2. Starting Day 14: Nivolumab application 240 mg i.v. over 30 minutes ever 2 weeks with a maximum to 2 years, or until disease progression or inacceptable toxicity.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Basel, Switzerland

Status

Recruiting

Address

Division of Medical Oncology and Cancer Immunology, University Hospital Basel

Basel, , 4031

Site Contact

Heinz Läubli, MD PhD

heinz.laeubli@usb.ch

+41 61 265 5074

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