Metastatic MelanomaPhase 2NCT00314093
RFT-5-dgA in Patients With Metastatic Melanoma
A Phase 2 study testing RFT5pdgA in people with Metastatic Melanoma, run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial summary
Background: CD4+ cells are white blood cells that regulate the immune system by controlling the strength and quality of the immune response. CD25+ cells are a subset of CD4+ cells that suppress or prevent immune responses. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Melanoma
- What is being tested?
- RFT5pdgA
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2006to Nov 2008
- 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
- Patients age greater than 18 with measurable metastatic melanoma that have an expected survival of greater than three months will be considered. Patients with resectable local/regional disease would undergo standard treatment with surgical resection and will not be eligible.
- Patients must be able to understand and give informed consent.
- Patients must have progressed while receiving standard therapy which may include IL-2; however, prior IL-2 therapy is not a requirement for enrollment.
- Serum creatinine of 1.6 mg/dl or less.
- Total bilirubin 2.0 mg/dl or less, except for patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.
- WBC 3000/mm(3) or greater.
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- Platelet count 90,000 mm(3) or greater
- Serum albumin greater than 2.5 g/dl,
- Serum AST/ALT less then 2.5 times normal,
- ECOG performance status of 0 or 1 or 2.
- For patients greater than 50 years of age or who have a history of cardiovascular disease a thallium stress test is required with EF greater than or equal to 45%.
- Patients of both genders must be willing to practice effective birth control during this trial.
- Patients must be willing to undergo leukapheresis.
Who cannot join
- Patients will be excluded:
- who are undergoing or have undergone in the past 3 weeks any other systemic form of therapy for their cancer.
- who received RFT5-dgA on another trial.
- who have uncontrolled concurrent illness including, but not limited to: ongoing or active infection; ongoing or active cardiac disease, such as symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia; or psychiatric illness/social situations that would limit compliance with study requirements.
- who require systemic steroid therapy upon entry into the trial.
- who are pregnant or breast-feeding.
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- who are known to be positive for hepatitis B(s)AG, hepatitis C or HIV antibody (because of possible immune effects of these conditions).
- who require chronic anticoagulation.
- who are 50 years old or greater who do not have a normal stress cardiac test (stress thallium, stress MUGA, dobutamine echocardiogram, or other stress test) with a LVEF less than 45%.
- who have history of EKG abnormalities, symptoms of cardiac ischemia or arrhythmias who do not have a normal stress cardiac test (stress thallium, stress MUGA, dobutamine echocardiogram, or other stress test) with a LVEF lea than 45%.
- who have any autoimmune diseases or immunodeficiency (including HIV),or other concurrent malignancies.
- Who have HAMA levels greater than 1 ug/mL.
- Who have had prior radiotherapy including radiotherapy to the lung, except for patients who have undergone localized soft tissue radiotherapy.
- Who have extensive lung disease where greater than 15% of the lung is involved based on CT evaluation.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Cancer Institute (NCI)
Bethesda, Maryland, 20892
About this study
Official title: Phase II Evaluation of RFT5-dgA in Patients With Metastatic Melanoma
Background:
- CD4+ cells are white blood cells that regulate the immune system by controlling the strength and quality of the immune response.
- CD25+ cells are a subset of CD4+ cells that suppress or prevent immune responses.
- RFT-5-dgA is an immunotoxin (substance that kills specific cells in the immune system) that kills CD25+ cells.
- In mouse studies, RFT-5-dgA showed anti-tumor activity in animals studies.
Read more
Objective: To determine whether the immune system of patients with metastatic melanoma (melanoma that has spread beyond the original site) can cause tumors to shrink if the patients are given RFT-5-dgA to remove their CD25+ cells.
Eligibility: Patients 18 years of age and older with metastatic melanoma whose disease has progressed after receiving standard treatment.
Design:
- Patients receive RFT-5-dgA through a vein every other day for a total of 3 doses (one treatment course). Patients have routine blood tests during the week of treatment.
- Four to 5 weeks after the last dose, patients are evaluated with a physical examination, blood tests and scans and x-rays to evaluate their tumor.
- Patients whose tumor has shrunk or remained stable may be offered additional treatment with RFT-5-dgA up to a total of four courses.
- Patients undergo leukapheresis or have several tubes of blood drawn from a vein to determine the effects of RFT-5-dgA on the immune system. This is done before the first dose of RFT-5-dgA, after the first three doses, and possibly during subsequent treatment courses in those patients who receive additional treatment. For leukapheresis, blood is collected through a needle in an arm vein and flows through a catheter into a machine that separates it into its components by spinning. The white cells are extracted and the rest of the blood is returned through another needle in the other arm.
Read the detailed description
Background:
- RFT5-dgA is an immunotoxin comprised of the IL-2Ra-specific murine IgG1 antibody RFT5 linked to deglycosylated ricin A chain (dgA) via the sterically hindered heterobifunctional disulfide linker SMPT (4-succinimidyl-oxycarbonyl-a-methyl-a-(2-pyridyldithio)-toluene).
- RFT5-dgA is a recombinant immunotoxin that selectively targets CD25 expressing cells in vivo. Further, treatment of human PBMC with RFT5-dgA in vitro results in the preferential depletion of CD25+ Treg cells.
- Depletion of Treg cells can enhance tumor protection to tumor-associated antigens expressed as self antigens and the RFT5-dgA immunotoxin had potent antitumor effects in SCID mice xenografted with L540 cells which express CD25.
- The MTD established in the phase I trial of RFT5-dgA was 15mg/m(2)/course IV.
Objectives:
- The primary objective is to determine whether objective clinical responses can be obtained in patients with metastatic melanoma following administration of RFT5-dgA.
- Secondary objectives will determine whether changes occur in levels of CD4+CD25+ regulatory T cells (Treg cells) in peripheral blood from before to after treatment and evaluate the toxicity profile of patients treated on this trial.
Eligibility:
- Patients greater than 18 years of age with measurable metastatic melanoma, an expected survival greater than three months, who have progressed after receiving standard therapy will be included.
- Standard clinical laboratory values must be normal for study inclusion and patients may not be pregnant, breast-feeding or require anticoagulation.
- Patients must be willing to undergo leukapheresis.
- Patients with active infections, other major medical disorders, HAMA levels greater than 1 ug/mL, or who have had prior radiotherapy or who have extensive lung disease will be excluded.
Design:
- Patients will receive 3 mg/m(2) RFT5-dgA intravenously every other day for a total of 3 doses (one course).
- Four to five weeks after the last dose, patients will undergo tumor evaluation, evaluation of changes in T-regulatory cells (CD4+CD25+cells and Foxp3 expression), and toxicity assessment.
- One additional course may be administered to patients with stable disease or partial or complete response.
- Up to 41 evaluable patients may be accrued to determine whether theRFT5-dgA can produce a modest response rate targeted to be 20 percent (p1=0.20)
- Enrollment reflects the anticipated enrollment. Actual enrollment is unknown due to no longer having access to the data as records were destroyed
- Conditions
- Metastatic Melanoma
- Being tested
- RFT5pdgA
- Keywords
- Clinical Response, Stage IV Melanoma, Immunotoxin, T Regulatory Cells, CD25+ Cells, Metastatic Melanoma
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RFT5pdgADrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Responses Can be Obtained in Following Administration of RFT5-dgA
The primary objective is to determine whether objective clinical responses can be obtained in patients with metastatic melanoma following administration of RFT5-dgA
Measured: up to one year
Secondary outcomes (2)
Determine Whether Changes Occur in Levels of CD4+CD25+ Regulatory T Cells (Treg Cells) in Peripheral Blood
Secondary objectives will determine whether changes occur in levels of CD4+CD25+ regulatory T cells (Treg cells) in peripheral blood from before to after treatment and evaluate the toxicity profile of patients treated on this trial.
Measured: Before to after treatment
Toxicity Profile
Secondary objectives will determine whether changes occur in levels of CD4+CD25+ regulatory T cells (Treg cells) in peripheral blood from before to after treatment and evaluate the toxicity profile of patients treated on this trial.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2006 (estimated)
- Study startApr 2006
- Primary completionNov 2008
- Study completionNov 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic MelanomaStudies of the same condition, open and under way.
- More trials run by University of Texas Southwestern Medical CenterThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- Single blind
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00314093
- Sponsor's protocol ID
- 060137
- Other IDs
- 06-C-0137
- Status last verified
- Oct 2019
- First submitted
- 11 Apr 2006
- Last updated
- 12 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Phan GQ, Yang JC, Sherry RM, Hwu P, Topalian SL, Schwartzentruber DJ, Restifo NP, Haworth LR, Seipp CA, Freezer LJ, Morton KE, Mavroukakis SA, Duray PH, Steinberg SM, Allison JP, Davis TA, Rosenberg SA. Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8372-7. doi: 10.1073/pnas.1533209100. Epub 2003 Jun 25.
PubMed 12826605
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Evaluation of RFT5-dgA in Patients With Metastatic Melanoma
- ClinicalTrials.gov ID
- NCT00314093
- Acronym / sponsor ID
- 060137
- Conditions
- Metastatic Melanoma
- Keywords
- Clinical Response, Stage IV Melanoma, Immunotoxin, T Regulatory Cells, CD25+ Cells, Metastatic Melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Apr 2006
- Primary completion
- Nov 2008 (actual)
- Study completion
- Nov 2008 (actual)
- First posted
- 12 Apr 2006 (estimated)
- Results
- Posted 12 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- CD4+ cells are white blood cells that regulate the immune system by controlling the strength and quality of the immune response.
- CD25+ cells are a subset of CD4+ cells that suppress or prevent immune responses.
- RFT-5-dgA is an immunotoxin (substance that kills specific cells in the immune system) that kills CD25+ cells.
- In mouse studies, RFT-5-dgA showed anti-tumor activity in animals studies.
Objective: To determine whether the immune system of patients with metastatic melanoma (melanoma that has spread beyond the original site) can cause tumors to shrink if the patients are given RFT-5-dgA to remove their CD25+ cells.
Eligibility: Patients 18 years of age and older with metastatic melanoma whose disease has progressed after receiving standard treatment.
Design:
- Patients receive RFT-5-dgA through a vein every other day for a total of 3 doses (one treatment course). Patients have routine blood tests during the week of treatment.
- Four to 5 weeks after the last dose, patients are evaluated with a physical examination, blood tests and scans and x-rays to evaluate their tumor.
- Patients whose tumor has shrunk or remained stable may be offered additional treatment with RFT-5-dgA up to a total of four courses.
- Patients undergo leukapheresis or have several tubes of blood drawn from a vein to determine the effects of RFT-5-dgA on the immune system. This is done before the first dose of RFT-5-dgA, after the first three doses, and possibly during subsequent treatment courses in those patients who receive additional treatment. For leukapheresis, blood is collected through a needle in an arm vein and flows through a catheter into a machine that separates it into its components by spinning. The white cells are extracted and the rest of the blood is returned through another needle in the other arm.
Detailed description
Background:
- RFT5-dgA is an immunotoxin comprised of the IL-2Ra-specific murine IgG1 antibody RFT5 linked to deglycosylated ricin A chain (dgA) via the sterically hindered heterobifunctional disulfide linker SMPT (4-succinimidyl-oxycarbonyl-a-methyl-a-(2-pyridyldithio)-toluene).
- RFT5-dgA is a recombinant immunotoxin that selectively targets CD25 expressing cells in vivo. Further, treatment of human PBMC with RFT5-dgA in vitro results in the preferential depletion of CD25+ Treg cells.
- Depletion of Treg cells can enhance tumor protection to tumor-associated antigens expressed as self antigens and the RFT5-dgA immunotoxin had potent antitumor effects in SCID mice xenografted with L540 cells which express CD25.
- The MTD established in the phase I trial of RFT5-dgA was 15mg/m(2)/course IV.
Objectives:
- The primary objective is to determine whether objective clinical responses can be obtained in patients with metastatic melanoma following administration of RFT5-dgA.
- Secondary objectives will determine whether changes occur in levels of CD4+CD25+ regulatory T cells (Treg cells) in peripheral blood from before to after treatment and evaluate the toxicity profile of patients treated on this trial.
Eligibility:
- Patients greater than 18 years of age with measurable metastatic melanoma, an expected survival greater than three months, who have progressed after receiving standard therapy will be included.
- Standard clinical laboratory values must be normal for study inclusion and patients may not be pregnant, breast-feeding or require anticoagulation.
- Patients must be willing to undergo leukapheresis.
- Patients with active infections, other major medical disorders, HAMA levels greater than 1 ug/mL, or who have had prior radiotherapy or who have extensive lung disease will be excluded.
Design:
- Patients will receive 3 mg/m(2) RFT5-dgA intravenously every other day for a total of 3 doses (one course).
- Four to five weeks after the last dose, patients will undergo tumor evaluation, evaluation of changes in T-regulatory cells (CD4+CD25+cells and Foxp3 expression), and toxicity assessment.
- One additional course may be administered to patients with stable disease or partial or complete response.
- Up to 41 evaluable patients may be accrued to determine whether theRFT5-dgA can produce a modest response rate targeted to be 20 percent (p1=0.20)
- Enrollment reflects the anticipated enrollment. Actual enrollment is unknown due to no longer having access to the data as records were destroyed
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- Single blind
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
Key exclusion criteria (14 listed)
- who are undergoing or have undergone in the past 3 weeks any other systemic form of therapy for their cancer.
- who received RFT5-dgA on another trial.
- who have uncontrolled concurrent illness including, but not limited to: ongoing or active infection; ongoing or active cardiac disease, such as symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia; or psychiatric illness/social situations that would limit compliance with study requirements.
- who require systemic steroid therapy upon entry into the trial.
- who are pregnant or breast-feeding.
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 |
|---|---|---|
| RFT5pdgA | Drug | – |
Primary outcome
Clinical Responses Can be Obtained in Following Administration of RFT5-dgA
Time frame: up to one year
The primary objective is to determine whether objective clinical responses can be obtained in patients with metastatic melanoma following administration of RFT5-dgA
2 secondary outcomes
Determine Whether Changes Occur in Levels of CD4+CD25+ Regulatory T Cells (Treg Cells) in Peripheral Blood
Time frame: Before to after treatment
Toxicity Profile
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 12826605Phan GQ, Yang JC, Sherry RM, Hwu P, Topalian SL, Schwartzentruber DJ, Restifo NP, Haworth LR, Seipp CA, Freezer LJ, Morton KE, Mavroukakis SA, Duray PH, Steinberg SM, Allison JP, Davis TA, Rosenberg SA. Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8372-7. doi: 10.1073/pnas.1533209100. Epub 2003 Jun 25.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing RFT5pdgA in people with Metastatic Melanoma, run by University of Texas Southwestern Medical Center 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 13 inclusion and 14 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: finished, as of the sponsor's last update on 12 Nov 2019. 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 12 Nov 2019). 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?
Clinical Responses Can be Obtained in Following Administration of RFT5-dgA (time frame: up to one year). 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 NCT00314093, which also lists 1 linked publication.
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 12 Nov 2019.