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

Phase 2
18 Years
Not Enrolling
Metastatic Melanoma, Metastatic Renal Cancer

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Trial Information

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


Zanolimumab is a human monoclonal antibody (mAb) that specifically recognizes CD4 protein
expressed on a subset of T lymphocytes and on monocytes from humans, and non-human primates.

Ongoing clinical studies have identified a 14 mg/kg dose of zanolimumab weekly as a safe and
efficacious dose. Toxicities of zanolimumab included headache, influenza-like illness,
injection/infusion site reaction, nasopharyngitis, pyrexia, diarrhea, fatigue, and cytokine
release syndrome at the time of infusion.

The current protocol is based on the hypothesis that transient elimination of CD4+
T-regulatory cells with zanolimumab will enhance the clinical effectiveness of aldesleukin
(IL-2) administration by decreasing T-regulatory cell generation.


Primary objective:

Determine the ability of a combination of aldesleukin and zanolimumab (anti-CD4 mAb)
administration to mediate tumor regression in patients with metastatic melanoma and
metastatic kidney cancer.

Secondary objectives:

Determine the rate of depletion and repopulation of CD4+ cells.

Determine the toxicity of this treatment.

Determine the potential for pharmacokinetic interaction between zanolimumab and aldesleukin.


Patients who are 18 years of age or older must have:

measurable metastatic melanoma or metastatic kidney cancer;

clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0, or 1.

Patients may not have:

previously received high dose aldesleukin.


Patients will receive zanolimumab at a dose of 14 mg/kg as an intravenous (i.v.) infusion
weekly for 9 weeks. After the fifth and seventh dose of zanolimumab, aldesleukin will
administered as an i.v. bolus at a dose of 720,000 IU/kg every 8 hours for a maximum of 15

Patients will undergo complete evaluation of tumor with physical examination, computed
tomography (CT) and clinical laboratory evaluation 2 weeks after zanolimumab administration.
If the patient has stable disease (SD) or tumor shrinkage, repeat complete evaluations will
be performed every 1-3 months. After the first year, patients continuing to respond will be
followed with this evaluation every 3-4 months until off study criteria are met.

If patients have stable disease or a partial response to treatment after the initial
evaluation, or if a patient recurs or progresses after a clinical response, they may be
eligible for re-treatment.

Patients will be entered into one of two strata: metastatic melanoma or metastatic renal
cancer. Each of the strata will be conducted using an optimal two-stage phase II design to
rule out an unacceptably low 15% clinical response rate, in favor of a modestly high
response rate of 35% (p1=0.35).

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

- Seronegative for hepatitis B antigen and hepatitis C antibody unless antigen

- 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

- 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.


- 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

- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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.

Outcome Description:

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.

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

David S Schrump, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)


United States: Federal Government

Study ID:




Start Date:

June 2010

Completion Date:

January 2012

Related Keywords:

  • Metastatic Melanoma
  • Metastatic Renal Cancer
  • Metastatic Melanoma
  • Metastatic Kidney Cancer
  • Clinical Performance
  • Tumor Regression
  • Toxicity
  • Carcinoma, Renal Cell
  • Kidney Neoplasms
  • Melanoma



National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, Maryland  20892