Recombinant Interleukin-15 in Treating Patients with Metastatic Melanoma or Kidney Cancer

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Status: Complete

Description

This phase I trial studies the side effects and best dose of recombinant interleukin-15 in treating patients with melanoma or kidney cancer that has spread to other parts of the body. Recombinant interleukin-15 is a substance that may help strengthen the body’s immune system and allow it to attack cancer or other diseases.

Eligibility Criteria

Inclusion Criteria

  • Diagnosis of metastatic malignant melanoma or metastatic renal cell cancer confirmed by the Laboratory of Pathology, National Cancer Institute (NCI)
  • Patients must have metastatic malignant melanoma or metastatic renal cell cancer (American Joint Committee on Cancer [AJCC] stage IV [M1] or equivalent disease); metastatic renal cell cancer patients must either have refused treatment with, have been unable to tolerate or have experienced progressive disease after treatment with sorafenib or sunitinib, and temsirolimus
  • Patients must have measurable disease
  • Diffusion capacity of the lung for carbon monoxide (DLCO)/DLCO corrected for alveolar volume (VA) and forced expiratory volume in one second (FEV-1.0) > 50% of predicted on pulmonary function tests
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x the upper limit of normal
  • Absolute neutrophil count >= 1,500/mm^3
  • Platelets >= 75,000/mm^3
  • Karnofsky performance status >= 70% or Eastern Cooperative Oncology Group (ECOG) =< 1
  • Serum creatinine of =< 1.5 X the upper limit of normal
  • Central nervous system (CNS) metastases: Patients who remain asymptomatic after successful definitive treatment of brain metastases (i.e., surgical resection, curative whole brain irradiation, stereotactic radiation therapy, or a combination of these) demonstrating stable or improved radiographic appearance on magnetic resonance imaging (MRI) scan >= 3 months after completion of treatment and no signs of cerebral edema are eligible

Exclusion Criteria

  • Patients must not have received any systemic corticosteroid therapy for 3 weeks prior to the start of therapy with the exception of physiological replacement doses of cortisone acetate or equivalent
  • Patients must not have received any cytotoxic therapy, immunotherapy, antitumor vaccines or monoclonal antibodies in the 4 weeks prior to the start of the study
  • History of any hematopoietic malignancy
  • Life expectancy of less than 3 months
  • Patients must not have a marked baseline prolongation of QT/corrected QT (QTc) interval (e.g., demonstration of a QTc interval > 500 milliseconds (ms)
  • Documented human immunodeficiency virus (HIV), active or chronic hepatitis B, hepatitis C or human T-lymphotropic virus (HTLV)-I infection * A positive hepatitis B serology indicative of previous immunization (i.e., hepatitis B surface antibody [HBsAb] positive and hepatitis C antibody [HBcAb] negative), or a fully resolved acute hepatitis B virus (HBV) infection is not an exclusion criterion * Positive hepatitis C serology is an exclusion criterion
  • Concurrent anticancer therapy (including other investigational agents)
  • History of severe asthma, presently on chronic medications (a history of mild asthma not requiring therapy is eligible)
  • History of autoimmune disease, with the exception of an autoimmune event associated with prior ipilimumab (anti-cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4]) therapy that has completely resolved for a period of more than 4 weeks
  • Inability or refusal to practice effective contraception during therapy or the presence of pregnancy or active breastfeeding (men and women of childbearing potential must use an effective method of birth control or abstinence during treatment and for four months after completion of treatment)
  • History of medical or psychiatric disease, active substance abuse or social circumstances which in the view of the principal investigator, would preclude safe treatment
  • Patients with cognitive impairment or likely to develop cognitive impairment while on study
  • Inability to give informed consent

Locations & Contacts

See trial information on ClinicalTrials.gov for a list of participating sites.

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the safety, toxicity profile, dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of recombinant human interleukin (IL)-15 (rhIL-15) in subjects with metastatic malignant melanoma and metastatic renal cell cancer.

SECONDARY OBJECTIVES:

I. Define the pharmacokinetic and pharmacodynamic characteristics of rhIL-15 in humans with the administration schedule defined above.

II. Determine the immunogenicity of rhIL-15 in subjects using a two-arm capture enzyme-linked immunosorbent assay (ELISA).

III. Obtain preliminary information on the effectiveness of rhIL-15 in increasing the proportion and absolute number of circulating natural killer (NK) cells, CD45RO+CD8+ T-cells and central or effector memory subsets based on expression of CD28, CD95, CCR7 and CD62L in study subjects by fluorescence-activated cell sorting (FACS) analysis.

IV. Obtain preliminary information on the antitumor effects of repeat cycles of rhIL-15 in patients with metastatic malignant melanoma and renal cell cancer.

OUTLINE:

Patients receive recombinant interleukin-15 intravenously (IV) over 30 minutes on days 1-12. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity for patients achieving response.

After completion of study treatment, patients are followed up for 3 months.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
NCI - Center for Cancer Research

Principal Investigator
Thomas Alexander Waldmann

Trial IDs

Primary ID 10-C-0021
Secondary IDs 9850, NCI-2015-00085, 100021
Clinicaltrials.gov ID NCT01021059