Phase II Study of Aldesleukin (IL-2) Following the Administration of Zanolimumab (Anti-CD4mAb) in Metastatic Melanoma and Metastatic Renal Cancer
| Status: | Terminated |
|---|---|
| Conditions: | Skin Cancer, Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/21/2016 |
| Start Date: | June 2010 |
| End Date: | January 2012 |
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.
- 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.
Background:
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.
Objectives:
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.
Eligibility:
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.
Design:
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
doses.
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).
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.
Objectives:
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.
Eligibility:
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.
Design:
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
doses.
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
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
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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