RFT-5-dgA in Patients With Metastatic Melanoma

NCT00314093 | Completed Phase 2 Results

• 2 other identifiers: 06013706-C-0137
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief 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.
• 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.

Conditions

Metastatic Melanoma

Keywords

Clinical Response; Stage IV Melanoma; Immunotoxin; T Regulatory Cells; CD25+ Cells; Metastatic Melanoma

Outcome Measures

Primary Outcomes (1)

• 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

  up to one year

Secondary Outcomes (2)

• Determine Whether Changes Occur in Levels of CD4+CD25+ Regulatory T Cells (Treg Cells) in Peripheral Blood

  Before to after treatment

• Toxicity Profile

Interventions

RFT5pdgA DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

National Cancer Institute (NCI)

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• 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.

  PMID: 12826605 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Limitations and Caveats

Sincere efforts were made to obtain the study data, but were unsuccessful as all study records have been destroyed

Results Point of Contact

• Title: Dr. Ellen Vitetta
• Organization: University of Texas Southwestern Medical Center

ELLEN.VITETTA@UTSouthwestern.edu

214-648-1200

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: SINGLE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2006
• First Posted: April 12, 2006
• Study Start: April 1, 2006
• Primary Completion: November 1, 2008
• Study Completion: November 1, 2008
• Last Updated: November 12, 2019
• Results First Posted: November 12, 2019

Record last verified: 2019-10

Locations

US (1)