Phase I Study of HeFi-1 in Refractory CD30-Positive Malignancy
The scientific basis for this study is the observation that antibodies directed at the
ligand-binding site of CD30 induce apoptosis in vitro and cure animals bearing CD30-positive
HeFi-1, a murine monoclonal antibody developed at the NCI, specifically binds human CD30, a
member of the tumor necrosis receptor superfamily, at the ligand-binding site.
CD30 is expressed on activated T-cells, Reed-Sternberg cells, anaplastic large cell
lymphoma, and some AIDS-related lymphoma cells.
Tumor cells from patients with anaplastic large cell lymphoma are sensitive to the effects
of HeFi-1 but Hodgkin's disease cell lines show variable responsiveness due to the presence
of mutations in I B kinase which result in constitutive activation of NF- B.
The primary objective of this study is to determine the toxicity and maximum tolerated dose
of HeFi-1 in patients with CD30-positive malignancy.
This study will explore the pharmacokinetics, dose required to saturate CD30 binding sites
in tumor aspirates, and the frequency and time course of onset of development of human
anti-mouse antibody (HAMA).
These studies will allow us to monitor in a preliminary fashion the clinical tumor response,
measured by reduction in tumor lesions and by following the tumor marker serum soluble
interleukin 2 receptor.
Patients with measurable or evaluable CD30-positive lymphoma who have become refractory to
standard therapy, including Hodgkin's disease, systemic anaplastic large cell lymphoma,
cutaneous T cell lymphoma and adult T cell leukemia/lymphoma are eligible for treatment.
This is a phase I dose-escalation trial in which cohorts of three patients will be treated
with HeFi-1 ranging from 0.5 to 5 mg/kg/dose (total dose of 2 to 20 mg/kg per treatment
Four doses will be given on an every three days schedule over a 10-day period for each
Two cycles of therapy will be administered provided the patient has had a partial or
complete response and has not developed dose-limiting toxicity or HAMA.
Primary Purpose: Treatment
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|
|Beth Israel Deaconess Medical Center||Boston, Massachusetts 02215|