Phase II Evaluation of RFT5-dgA in Patients With Metastatic Melanoma
- 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
- 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
- One additional course may be administered to patients with stable disease or partial or
- 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)
Primary Purpose: Treatment
United States: Federal Government
|National Cancer Institute (NCI)||Bethesda, Maryland 20892|