AzTrials
AzTrials

Metastatic MelanomaPhase 2NCT01160445

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

A Phase 2 study testing Zanolimumab and Aldesleukin in people with Metastatic Melanoma and Metastatic Renal Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Melanoma, Metastatic Renal Cancer
What is being tested?
Zanolimumab and Aldesleukin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteUnited States
Study dates
Jun 2010to Jan 2012
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 23Show fewer
  • 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.

Who cannot join

  • 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
Show all 13Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

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.
Read more

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.
Read the detailed description

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).

Being tested
Zanolimumab, Aldesleukin
Keywords
Metastatic Melanoma, Metastatic Kidney Cancer, Clinical Performance, Tumor Regression, Toxicity
Medical subject headings
Melanoma, Kidney Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ZanolimumabDrug

    Also called HuMax-CD4

    14 mg/kg as an intravenous infusion weekly (+/- 3 days) for 9 weeks.

  • AldesleukinDrug

    Also called IL-2

    720,000 IU/kg every 8 hours for a maximum of 15 doses.

Study groups in NCT01160445
Study groupRoleWhat they receive
HD IL-2 + Zanolimumab - MelanomaExperimentalPatients 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.
Receives: Drug: Zanolimumab; Drug: Aldesleukin
HD IL-2 + Zanolimumab - Renal CellExperimentalPatients 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.
Receives: Drug: Zanolimumab; Drug: Aldesleukin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 2 years

Secondary outcomes (1)

  1. Toxicity of Zanolimumab and IL-2 Treatment Regimen

    Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.

    Measured: 10 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jul 2010 (estimated)
  2. Study startJun 2010
  3. Primary completionJan 2012
  4. Study completionJan 2012

Why it stopped: The study was terminated because we were not able to obtain the study drug.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01160445
Sponsor's protocol ID
100145
Other IDs
10-C-0145
Status last verified
Sep 2015
First submitted
9 Jul 2010
Last updated
28 Oct 2015
Data monitoring committee
No

Publications

  • Ahmadzadeh M, Antony PA, Rosenberg SA. IL-2 and IL-15 each mediate de novo induction of FOXP3 expression in human tumor antigen-specific CD8 T cells. J Immunother. 2007 Apr;30(3):294-302. doi: 10.1097/CJI.0b013e3180336787.

    PubMed 17414320

  • Rosenberg SA. A new era for cancer immunotherapy based on the genes that encode cancer antigens. Immunity. 1999 Mar;10(3):281-7. doi: 10.1016/s1074-7613(00)80028-x. No abstract available.

    PubMed 10204484

  • Asano M, Toda M, Sakaguchi N, Sakaguchi S. Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation. J Exp Med. 1996 Aug 1;184(2):387-96. doi: 10.1084/jem.184.2.387.

    PubMed 8760792

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Zanolimumab and Aldesleukin in people with Metastatic Melanoma and Metastatic Renal Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 28 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Dec 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary 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. (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01160445, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2015.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in