Kidney CancerPhase 1NCT00492440
Interleukin-7 in Treating Patients With Metastatic Melanoma or Locally Advanced or Metastatic Kidney Cancer
A Phase 1 study testing recombinant interleukin-7, gene expression analysis and polymerase chain reaction in people with Kidney Cancer and Melanoma (Skin), run by Cytheris SA at 1 site in United States.
Trial summary
RATIONALE: Interleukin-7 may stimulate the white blood cells to kill tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of interleukin-7 in treating patients with metastatic melanoma or locally advanced or metastatic kidney cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Cancer, Melanoma (Skin)
- What is being tested?
- recombinant interleukin-7, gene expression analysis and polymerase chain reaction
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- May 2007to Dec 2010
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
DISEASE CHARACTERISTICS:
- Histologically confirmed diagnosis of 1 of the following:
- Melanoma
- Metastatic disease
- Renal cell carcinoma
- Locally advanced and unresectable disease OR metastatic disease
- Refractory to standard therapy OR ineligible to receive standard therapy
- Measurable or evaluable disease
- Previously received high-dose interleukin-2 OR have a contraindication for this treatment
- No previously untreated or unstable brain metastases
- No splenic metastasis
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Life expectancy ≥ 3 months
- Absolute neutrophil count > 1,000/mm^3
- Platelet count > 100,000/mm^3
- PT/PTT ≤ 1.5 times upper limit of normal (ULN)
- Creatinine < 1.5 times ULN
- AST and ALT < 2.5 times ULN
- Conjugated (Direct) bilirubin ≤ 1.25 times ULN
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- LVEF ≥ 45% by cardiac stress test (e.g., stress thallium, stress MUGA, dobutamine echocardiogram, or other stress test) for patients meeting any of the following criteria:
- History of ECG abnormalities
- Symptoms of cardiac ischemia
- At least 50 years of age and over
- Familial or personal history of heart failure
- Previously treated with antimitotic agents susceptible to trigger heart failure
- FEV_1 > 60% of predicted (for patients with a prolonged smoking history or symptoms of respiratory dysfunction)
- No concurrent cognitive impairment or likelihood of developing cognitive impairment on study therapy
- No concurrent splenomegaly or proliferative hematologic disease
- No documented HIV positivity
- No acute hepatitis A or hepatitis B or C
- Positive hepatitis B serology indicative of previous immunization (i.e., HBs Ab positive and HBc Ab negative) allowed
- Positive hepatitis C serology allowed provided HCV RNA load by PCR is negative
- Resting blood pressure ≤ 140/90 mm Hg on standard antihypertensive therapy
- Untreated hypertensive patients who received standard antihypertensive therapy allowed provided hypertension is well controlled
- No QTc prolongation ≥ 470 msec
- No prior history of cardiovascular disease, arrhythmias, or significant ECG abnormalities
- No active infection requiring systemic treatment and/or hospitalization within the past 28 days
- Patients who have completed therapy or are clinically stable on therapy, in the opinion of the investigator, are eligible
- No history of autoimmune disease
- No history of severe asthma
- No history of medical or psychiatric disease that would preclude study treatment
- No documented cirrhosis or documented acute hepatitis
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- More than 2 weeks since prior systemic corticosteroid therapy
- More than 4 weeks since prior and no other concurrent cytotoxic therapy, immunotherapy, biological agents (i.e., cytokines, growth factors, or monoclonal antibodies), or antitumor vaccines
- More than 7 days since prior hepatotoxic drugs unless medically necessary
- More than 2 days since prior alcohol consumption
- More than 1 day since prior acetaminophen use
- No prior splenectomy
- No prior allogeneic hematopoietic stem cell transplantation or solid organ transplantation
- No concurrent palliative therapy
- No concurrent chemotherapy
- No concurrent chronic anticoagulation (i.e., high-dose warfarin or heparin)
- Warfarin dose 1 to 2 mg/day allowed
- No concurrent chronic medications for asthma
- No other concurrent investigational agents
Trial locations and contacts
1 site in 1 country.
United States1 site
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, 20892-1182
About this study
Official title: A Phase I Study of Subcutaneous "CYT 107" (Interleukin-7) in Refractory Metastatic Melanoma or Renal Cell Carcinoma
RATIONALE: Interleukin-7 may stimulate the white blood cells to kill tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of interleukin-7 in treating patients with metastatic melanoma or locally advanced or metastatic kidney cancer.
Read the detailed description
OBJECTIVES:
Primary
- Determine the safety of recombinant interleukin-7 (IL-7) in patients with metastatic melanoma or locally advanced or metastatic renal cell carcinoma.
- Confirm the previously documented safety profile of non-glycosylated IL-7 in these patients.
- Determine the safety of higher doses of recombinant IL-7 in these patients.
- Determine the maximum tolerated dose of recombinant IL-7 in these patients.
- Determine the biologically active dose of recombinant IL-7 in these patients.
Secondary
- Determine the pharmacokinetics and pharmacodynamics of recombinant IL-7 in these patients.
- Compare the biological and clinical effects of recombinant IL-7 with non-glycosylated IL-7 in these patients.
- Determine the potential antitumor effect of recombinant IL-7 in these patients.
- Determine the dose and administration schedule of recombinant IL-7 in these patients.
OUTLINE: This is a dose-escalation study. Patients are stratified according to lymphocyte count (normal lymphocyte count [CD4+ T cells > 400/mm^3] vs lymphopenic [CD4+ T cells < 400/mm^3]). Patients are assigned to 1 of 2 treatment groups.
- Group 1 (normal lymphocyte count): Patients receive recombinant interleukin-7 (IL-7) subcutaneously once a week (to determine an active dose) for up to 3 weeks in the absence of disease progression or unacceptable toxicity.
- Group 2 (lymphopenic): Patients receive recombinant IL-7 subcutaneously once a week for up to 3 weeks at one dose level below the active dose determined in group 1.
Cohorts of 3-6 patients from each group receive escalating doses of recombinant IL-7 until the maximum tolerated dose (MTD) is determined. The MTD is the defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Up to 30 additional patients may be treated at the MTD.
Patients undergo blood and bone marrow collection periodically for pharmacokinetic, pharmacodynamic, and immunological studies. Samples are analyzed for the presence of antibodies and proteins via ELISA; CD3, CD4, and CD8 T cell counts, CD127, Ki-67, and Bcl-2 expression in CD4+ and CD8+ T cells, and CD19 B cell counts via flow cytometry; and clonal B cell proliferation via PCR and flow cytometry.
After completion of study treatment, patients are followed at 3 months.
- Conditions
- Kidney Cancer, Melanoma (Skin)
- Being tested
- recombinant interleukin-7, gene expression analysis, polymerase chain reaction, protein expression analysis, flow cytometry
- Keywords
- recurrent renal cell cancer, stage IV renal cell cancer, stage III renal cell cancer, recurrent melanoma, stage IV melanoma
- Medical subject headings
- Kidney Neoplasms, Melanoma, Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
recombinant interleukin-7Biological
gene expression analysisGenetic
polymerase chain reactionGenetic
protein expression analysisGenetic
flow cytometryOther
immunoenzyme techniqueOther
immunologic techniqueOther
laboratory biomarker analysisOther
| Study group | Role | What they receive |
|---|---|---|
| CYT107 (r-hIL-7) | Experimental | Not described Receives: Biological: recombinant interleukin-7; Genetic: gene expression analysis; Genetic: polymerase chain reaction; Genetic: protein expression analysis; Other: flow cytometry; Other: immunoenzyme technique; Other: immunologic technique; Other: laboratory biomarker analysis; Other: pharmacological study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of recombinant interleukin-7 (IL-7)
Secondary outcomes (4)
Pharmacokinetics and pharmacodynamics of IL-7
Comparison of the biological and clinical effects of recombinant IL-7 with non glycosylated IL-7
Potential antitumor effect of recombinant IL-7
Dose and administration schedule of recombinant IL-7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2007 (estimated)
- Study startMay 2007
- Primary completionJul 2010
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cytheris SA
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Cytheris, Inc.
- Responsible party
- Sponsor
- Investigators
- Steven A. Rosenberg, MD, PhD, Study chair, NCI - Surgery Branch
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00492440
- Sponsor's protocol ID
- CLI-107-04
- Other IDs
- 07-C-0114, CLI-107-04
- Status last verified
- Oct 2012
- First submitted
- 25 Jun 2007
- Last updated
- 18 Oct 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Subcutaneous "CYT 107" (Interleukin-7) in Refractory Metastatic Melanoma or Renal Cell Carcinoma
- ClinicalTrials.gov ID
- NCT00492440
- Acronym / sponsor ID
- CLI-107-04
- Conditions
- Kidney Cancer, Melanoma (Skin)
- Keywords
- recurrent renal cell cancer, stage IV renal cell cancer, stage III renal cell cancer, recurrent melanoma, stage IV melanoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Cytheris SAIndustry (pharma, biotech, devices)
- Collaborators
- Cytheris, Inc.
- Study start
- May 2007
- Primary completion
- Jul 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 27 Jun 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Interleukin-7 may stimulate the white blood cells to kill tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of interleukin-7 in treating patients with metastatic melanoma or locally advanced or metastatic kidney cancer.
Detailed description
OBJECTIVES:
Primary
- Determine the safety of recombinant interleukin-7 (IL-7) in patients with metastatic melanoma or locally advanced or metastatic renal cell carcinoma.
- Confirm the previously documented safety profile of non-glycosylated IL-7 in these patients.
- Determine the safety of higher doses of recombinant IL-7 in these patients.
- Determine the maximum tolerated dose of recombinant IL-7 in these patients.
- Determine the biologically active dose of recombinant IL-7 in these patients.
Secondary
- Determine the pharmacokinetics and pharmacodynamics of recombinant IL-7 in these patients.
- Compare the biological and clinical effects of recombinant IL-7 with non-glycosylated IL-7 in these patients.
- Determine the potential antitumor effect of recombinant IL-7 in these patients.
- Determine the dose and administration schedule of recombinant IL-7 in these patients.
OUTLINE: This is a dose-escalation study. Patients are stratified according to lymphocyte count (normal lymphocyte count [CD4+ T cells > 400/mm^3] vs lymphopenic [CD4+ T cells < 400/mm^3]). Patients are assigned to 1 of 2 treatment groups.
- Group 1 (normal lymphocyte count): Patients receive recombinant interleukin-7 (IL-7) subcutaneously once a week (to determine an active dose) for up to 3 weeks in the absence of disease progression or unacceptable toxicity.
- Group 2 (lymphopenic): Patients receive recombinant IL-7 subcutaneously once a week for up to 3 weeks at one dose level below the active dose determined in group 1.
Cohorts of 3-6 patients from each group receive escalating doses of recombinant IL-7 until the maximum tolerated dose (MTD) is determined. The MTD is the defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Up to 30 additional patients may be treated at the MTD.
Patients undergo blood and bone marrow collection periodically for pharmacokinetic, pharmacodynamic, and immunological studies. Samples are analyzed for the presence of antibodies and proteins via ELISA; CD3, CD4, and CD8 T cell counts, CD127, Ki-67, and Bcl-2 expression in CD4+ and CD8+ T cells, and CD19 B cell counts via flow cytometry; and clonal B cell proliferation via PCR and flow cytometry.
After completion of study treatment, patients are followed at 3 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CYT107 (r-hIL-7) | Experimental | Biological: recombinant interleukin-7, Genetic: gene expression analysis, Genetic: polymerase chain reaction, Genetic: protein expression analysis, Other: flow cytometry, Other: immunoenzyme technique, Other: immunologic technique, Other: laboratory biomarker analysis, Other: pharmacological study |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| recombinant interleukin-7 | Biological | CYT107 (r-hIL-7) |
| gene expression analysis | Genetic | CYT107 (r-hIL-7) |
| polymerase chain reaction | Genetic | CYT107 (r-hIL-7) |
| protein expression analysis | Genetic | CYT107 (r-hIL-7) |
| flow cytometry | Other | CYT107 (r-hIL-7) |
| immunoenzyme technique | Other | CYT107 (r-hIL-7) |
| immunologic technique | Other | CYT107 (r-hIL-7) |
| laboratory biomarker analysis | Other | CYT107 (r-hIL-7) |
| pharmacological study | Other | CYT107 (r-hIL-7) |
Primary outcome
Safety of recombinant interleukin-7 (IL-7)
4 secondary outcomes
Pharmacokinetics and pharmacodynamics of IL-7
Comparison of the biological and clinical effects of recombinant IL-7 with non glycosylated IL-7
Potential antitumor effect of recombinant IL-7
Dose and administration schedule of recombinant IL-7
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven A. Rosenberg, MD, PhD study chair
NCI - Surgery Branch
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing recombinant interleukin-7, gene expression analysis and polymerase chain reaction in people with Kidney Cancer and Melanoma (Skin), run by Cytheris SA 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?
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 18 Oct 2012. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
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?
Safety of recombinant interleukin-7 (IL-7). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Oct 2012.