Phase II Study of Aldesleukin (IL-2) Following the Administration of Zanolimumab (Anti-CD4mAb) in Metastatic Melanoma and Metastatic Renal Cancer

This study has been terminated.
(The study was terminated because we were not able to obtain the study drug.)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01160445
First received: July 9, 2010
Last updated: November 7, 2012
Last verified: November 2012
  Purpose

Background:

  • Aldesleukin (IL-2) is a drug that can help to shrink tumors in some patients with metastatic renal cancer and metastatic melanoma. It is possible that removing certain white blood cells (known as CD4 cells) before IL-2 treatment may improve the treatment effects.
  • Zanolimumab is an antibody that works by destroying CD4 cells in the blood. Researchers are interested in determining whether zanolimumab can improve the results of IL-2 treatment if it is given before, during, and after IL-2 treatment. In addition, further research with zanolimumab may provide more information on how IL-2 treatment causes tumors to stop growing or shrink.

Objectives:

- To evaluate the effectiveness of IL-2 treatment in conjunction with zanolimumab in individuals with metastatic cancer.

Eligibility:

- Individuals at least 18 years of age who have been diagnosed with metastatic melanoma or metastatic kidney cancer.

Design:

  • Eligible participants will be screened with a full physical examination and medical history, imaging studies, and blood samples, including leukapheresis, to remove a sample of white blood cells for testing purposes. Participants may also have a colonoscopy and biopsies if they have received previous treatments that have been known to cause colon damage.
  • Participants will be treated with zanolimumab and IL-2 treatment for 9 weeks.
  • Zanolimumab will be given on an outpatient basis during weeks 1 through 4, 6, 8, and 9. In weeks 5 and 7, participants will receive zanolimumab as an inpatient in addition to IL-2 therapy.
  • Inpatient IL-2 treatment will be given during weeks 5 and 7. Up to 15 doses of IL-2 treatment will be given over a maximum of 5 days, followed by inpatient recovery time.
  • During week 5, participants will have tumor imaging studies prior to receiving zanolimumab and IL-2 treatment.
  • About 2 weeks after the treatment period, participants will return to the clinical center for a 2-day evaluation with a physical examination, imaging studies, and blood samples.
  • Participants whose tumors have responded to treatment will be offered up to two additional courses of treatment, starting 6 to 8 weeks after the last IL-2 dose. Subsequent courses will be given exactly as described above in the initial course of treatment. Participants whose tumors do not respond to treatment will have follow-up evaluations as required by the study researchers.

Condition Intervention Phase
Metastatic Melanoma
Metastatic Renal Cancer
Drug: Zanolimumab
Drug: Aldesleukin
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Aldesleukin (IL-2) Following the Administration of Zanolimumab (Anti-CD4mAb) in Metastatic Melanoma and Metastatic Renal Cancer

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • The Ability of a Combination of Aldesleukin (IL-2) and Zanolimumab (Anti-CD4 mAb) Administration to Mediate Tumor Regression in Patients With Metastatic Melanoma and Metastatic Kidney Cancer. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Tumor regression was assessed by the Response Criteria in Solid Tumors (RECIST). Complete response (CR) is disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Progressive disease (PD) is at least a 20% in the sum of the longest diameter (LD) recorded since the treatment started. Stable disease (SD) is neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for PD taking as reference the smallest sum LD.


Secondary Outcome Measures:
  • Toxicity of Zanolimumab and IL-2 Treatment Regimen [ Time Frame: 10 months ] [ Designated as safety issue: Yes ]
    Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.


Enrollment: 9
Study Start Date: June 2010
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HD IL-2 + Zanolimumab - Melanoma

Patients with metastatic melanoma Zanolimumab 14 mg/kg as an intravenous infusion weekly (+/- 3 days) for 9 weeks.

Aldesleukin (IL-2) 720,000 IU/kg every 8 hours for a maximum of 15 doses.

Drug: Zanolimumab
14 mg/kg as an intravenous infusion weekly (+/- 3 days) for 9 weeks.
Other Name: HuMax-CD4
Drug: Aldesleukin
720,000 IU/kg every 8 hours for a maximum of 15 doses.
Other Name: IL-2
Experimental: HD IL-2 + Zanolimumab - Renal Cell

Patients with metastatic renal cancer Zanolimumab 14 mg/kg as an intravenous infusion weekly (+/- 3 days) for 9 weeks.

Aldesleukin (IL-2) 720,000 IU/kg every 8 hours for a maximum of 15 doses.

Drug: Zanolimumab
14 mg/kg as an intravenous infusion weekly (+/- 3 days) for 9 weeks.
Other Name: HuMax-CD4
Drug: Aldesleukin
720,000 IU/kg every 8 hours for a maximum of 15 doses.
Other Name: IL-2

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Measurable metastatic melanoma or metastatic renal cancer. Metastatic cancer diagnosis will be confirmed by the Laboratory of Pathology at the National Cancer Institute (NCI).
  • Patients must never have received high dose aldesleukin.
  • Greater than or equal to 18 years of age.
  • Willing to sign a durable power of attorney
  • Able to understand and sign the Informed Consent Document
  • 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 for four months after receiving 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 hepatitis C antibody unless antigen negative.
    • Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the therapy on the fetus.
  • Hematology:

    • Absolute neutrophil count greater than 1000/mm^3 without the support of filgrastim.
    • White blood cell (WBC) (greater than 3000/mm^3).
    • Platelet count greater than 100,000/mm^3.
    • Hemoglobin greater than 8.0 g/dl.
  • Chemistry:

    • Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less or equal to 2.5 times the upper limit of normal.
    • Serum creatinine less than or equal to 1.6 mg/dl.
    • Total bilirubin less than or equal to 1.5 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 zanolimumab, and patient's toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo).
  • Six weeks must have elapsed since prior anti-cytotoxic T-lymphocyte antigen 4 (CTLA4) antibody therapy to allow antibody levels to decline, and patients who have previously received anti-CTLA4 antibody and have documented gastrointestinal (GI) toxicity must have a normal colonoscopy with normal colonic biopsies.

EXCLUSION CRITERIA:

  • Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the therapy on the fetus or infant.
  • Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
  • 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).
  • Concurrent systemic steroid therapy
  • History of severe immediate hypersensitivity reaction to any of the agents used in this study. History of coronary revascularization or ischemic symptoms
  • Any patient known to have an left ventricular ejection fraction (LVEF) less than or equal to 45%.
  • Documented LVEF of less than or equal to 45% tested in patients with:

    • History of ischemic heart disease, chest pain, or clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block
    • Age greater than or equal to 60 years old.
  • Documented forced expiratory volume 1 (FEV1) less than or equal to 60% predicted tested in patients with:

    • A prolonged history of cigarette smoking (20 pack year of smoking within the past 2 years).
    • Symptoms of respiratory dysfunction
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01160445

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: David S Schrump, M.D. National Cancer Institute (NCI)
  More Information

Publications:
Responsible Party: Steven A. Rosenberg, M.D./National Cancer Institute, National Institutes of Health
ClinicalTrials.gov Identifier: NCT01160445     History of Changes
Other Study ID Numbers: 100145, 10-C-0145
Study First Received: July 9, 2010
Results First Received: November 7, 2012
Last Updated: November 7, 2012
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by National Institutes of Health Clinical Center (CC):
Metastatic Melanoma
Metastatic Kidney Cancer
Clinical Performance
Tumor Regression
Toxicity

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Kidney Neoplasms
Melanoma
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nevi and Melanomas
Aldesleukin
Interleukin-2
Antibodies, Monoclonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 09, 2014