RFT-5-dgA in Patients With Metastatic Melanoma
- 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.
- 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.
|Study Design:||Intervention Model: Single Group Assignment
Masking: Single Blind
Primary Purpose: Treatment
|Official Title:||Phase II Evaluation of RFT5-dgA in Patients With Metastatic Melanoma|
|Study Start Date:||April 2006|
|Study Completion Date:||November 2008|
|Primary Completion Date:||November 2008 (Final data collection date for primary outcome measure)|
- 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.
- 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.
- 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.
- 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)
|United States, Maryland|
|National Cancer Institute (NCI)|
|Bethesda, Maryland, United States, 20892|