RFT-5-dgA in Patients With Metastatic Melanoma
This study has been completed.
Sponsor:
University of Texas Southwestern Medical Center
Collaborator:
Information provided by (Responsible Party):
Ellen Vitetta, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:
NCT00314093
First received: April 11, 2006
Last updated: July 11, 2012
Last verified: March 2006
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Metastatic Melanoma |
Drug: RFT5pdgA |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Primary Purpose: Treatment |
| Official Title: | Phase II Evaluation of RFT5-dgA in Patients With Metastatic Melanoma |
Resource links provided by NLM:
Further study details as provided by University of Texas Southwestern Medical Center:
| Estimated Enrollment: | 41 |
| Study Start Date: | April 2006 |
| Study Completion Date: | November 2008 |
| Primary Completion Date: | November 2008 (Final data collection date for primary outcome measure) |
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)
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
INCLUSION CRITERIA:
- 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.
- 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.
EXCLUSION CRITERIA:
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.
- 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.
Contacts and Locations More Information
Additional Information:
Publications:
| Responsible Party: | Ellen Vitetta, Director, University of Texas Southwestern Medical Center |
| ClinicalTrials.gov Identifier: | NCT00314093 History of Changes |
| Obsolete Identifiers: | NCT00331461 |
| Other Study ID Numbers: | 060137, 06-C-0137 |
| Study First Received: | April 11, 2006 |
| Last Updated: | July 11, 2012 |
| Health Authority: | United States: Federal Government |
Keywords provided by University of Texas Southwestern Medical Center:
|
Clinical Response Stage IV Melanoma Immunotoxin |
T Regulatory Cells CD25+ Cells Metastatic Melanoma |
Additional relevant MeSH terms:
|
Melanoma Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal |
Neoplasms by Histologic Type Neoplasms Neoplasms, Nerve Tissue Nevi and Melanomas |
ClinicalTrials.gov processed this record on May 22, 2013