Cyclophosphamide, Fludarabine, Tumor Infiltrating Lymphocytes, and Aldesleukin in Treating Participants with Metastatic Uveal Melanoma

Status: Active

Description

This phase II trial studies how well cyclophosphamide, fludarabine, tumor infiltrating lymphocytes, and aldesleukin work in treating participants with uveal melanoma that has spread to other places in the body. Drugs used in chemotherapy, such as cyclophosphamide and fludarabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Tumor infiltrating lymphocytes may be an effective treatment for uveal melanoma. Aldesleukin may stimulate white blood cells to kill uveal melanoma cells. Giving cyclophosphamide, fludarabine, tumor infiltrating lymphocytes, and aldesleukin may kill more tumor cells.

Eligibility Criteria

Inclusion Criteria

  • Measurable metastatic uveal melanoma
  • Patients must be co-enrolled on the companion protocol HCC 17-220 (Cell Harvest and Preparation to Support Adoptive Cell Therapy Clinical Protocols and Pre-Clinical Studies) and have available TIL cultures for therapy
  • Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible. Patients with surgically resected brain metastases are eligible
  • Able to understand and sign the informed consent document
  • Willing to sign a durable power of attorney
  • Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1
  • Life expectancy of greater than three months
  • Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for up to four months after receiving the treatment
  • Serology: * Seronegative for human immunodeficiency virus (HIV) antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune-competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities) * Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by reverse transcription-polymerase chain reaction (RT-PCR) and be hepatitis C virus (HCV) ribonucleic acid (RNA) negative
  • Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus
  • Absolute neutrophil count greater than 1000/mm3 without the support of filgrastim
  • White blood cell (WBC) >= 3000/mm3
  • Platelet count >= 100,000/mm3
  • Hemoglobin > 8.0 g/dl
  • Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =< to 3.5 times the upper limit of normal
  • Serum creatinine =< to 1.6 mg/dl
  • Total bilirubin =< to 2.0 mg/dl, except in patients with Gilbert’s syndrome who must have a total bilirubin less than 3.0 mg/dl
  • More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients’ toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo). (Note: Patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less)

Exclusion Criteria

  • Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant
  • Any form of primary immunodeficiency (such as severe combined immunodeficiency disease)
  • Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities)
  • Active systemic infections (e.g.: requiring anti-infective treatment), coagulation disorders or any other active major medical illnesses
  • History of major organ autoimmune disease
  • Concurrent systemic steroid therapy
  • History of severe immediate hypersensitivity reaction to any of the agents used in this study
  • History of active coronary or ischemic symptoms
  • Documented left ventricular ejection fraction (LVEF) of less than or equal to 45%; note: testing is required in patients with: * Age >= 65 years’ old * Clinically significant atrial and or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or have a history of ischemic heart disease, chest pain
  • Documented forced expiratory volume in 1 second (FEV1) less than or equal to 60% predicted tested in patients with: * A prolonged history of cigarette smoking (20 packs [pk]/year of smoking within the past 2 years). * Symptoms of respiratory dysfunction
  • Patients who are receiving any other investigational agents

Locations & Contacts

Pennsylvania

Pittsburgh
University of Pittsburgh Cancer Institute (UPCI)
Status: Active
Contact: Udai S. Kammula
Phone: 412-623-7712
Email: kammulaus@upmc.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To evaluate the efficacy of a non-myeloablative lymphodepleting preparative regimen followed by infusion of autologous tumor infiltrating lymphocyte (TIL) and high-dose aldesleukin in patients with metastatic uveal melanoma using the objective response rate (ORR).

SECONDARY OBJECTIVES:

I. To further evaluate the efficacy of this therapy using complete response (CR) rate, duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).

II. To characterize the safety profile of this therapy in patients with metastatic uveal melanoma.

OUTLINE:

Participants receive cyclophosphamide intravenously (IV) over 1 hour on days -7 and -6, fludarabine IV over 30 minutes on days -5 to -1, TIL IV over 20-30 minutes on day 0, and aldesleukin IV over 15 minutes every 8 hours for up to 6 doses on day 0 in the absence of disease progression or unaccepted toxicity. Participants who have stable disease, a partial response to treatment, or recur after initially responding to treatment may receive a second course.

After completion of study treatment, participants are followed up at 6 and 12 weeks, every 3 months for 9 months, and then every 6 months for 1 year.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
University of Pittsburgh Cancer Institute (UPCI)

Principal Investigator
Udai S. Kammula

Trial IDs

Primary ID 17-219
Secondary IDs NCI-2018-00881
Clinicaltrials.gov ID NCT03467516