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.
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.
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).
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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.
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.
David S Schrump, M.D.
National Cancer Institute (NCI)
United States: Federal Government
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