Phase I Study of HeFi-1 in Refractory CD30-Positive Malignancy
18 Years
N/A
Both
Neoplasms
Trial Information
Phase I Study of HeFi-1 in Refractory CD30-Positive Malignancy
BACKGROUND:
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
tumors.
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.
OBJECTIVE:
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.
ELIGIBILITY:
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.
DESIGN:
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
course).
Four doses will be given on an every three days schedule over a 10-day period for each
cycle.
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.
Inclusion Criteria
- INCLUSION CRITERIA:
All Patients must have a histologically confirmed diagnosis of malignancy by department of
pathology at the enrolling institution.
Tumor cells must express CD30. CD30 expression will be verified by immunohistochemistry.
At least 30% of tumor cells must be CD30 positive. CD30 staining will be performed on
existing tissue blocks and on fresh tumor tissue if a biopsy is performed.
Patients must have measurable or evaluable disease.
The patient must have a granulocyte count of at least 1000/mm(3) and a platelet count of
50,000/mm(3) without transfusion.
Patients must have a creatinine of less than 2.0 mg/dL.
Omission of cyotoxic chemotherapy and systemic steroids for 3 weeks prior to entry into
the trial is required. Topical and inhaled steroids will be permitted.
Patients must have a life expectancy of greater than 2 months.
Eligible patients must be greater than or equal to 18 years old. There is no upper age
limit.
Patients must have SGOT and SGPT value less than or equal to 2.0-fold greater than the
upper limit of normal and bilirubin less than or equal to 2.0 mg/dL.
Patients must be able to understand and sign an Informed Consent form.
Karnofsky Performance Status greater than or equal to 70%.
EXCLUSION CRITERIA:
Patients with central nervous system disease as assessed by clinical examination. If the
clinical findings suggest the presence of CNS disease a lumbar puncture should be done.
Pregnant and nursing patients are not eligible for the study because the effects of HeFi-1
on the developing fetus and the nursing infant are unknown. All patients must agree to
use effective contraceptive measures while receiving therapy and for two weeks afterwards.
HIV positive patients are excluded from the study because the toxicity may be different in
this population.
Hepatitis B surface antigen positive and Hepatitis C antibody positive patients are
excluded because the toxicity of therapy may be different in this population.
Patients who previously received murine monoclonal antibody therapy are ineligible.
Patients who are HAMA positive.
Patients with significant renal, pulmonary, cardiovascular, endocrine, rheumatologic or
allergic disease should be excluded.
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Authority:
United States: Federal Government
Study ID:
030038
NCT ID:
NCT00048880
Start Date:
November 2002
Completion Date:
July 2008
Related Keywords:
- Neoplasms
- Anaplastic Large Cell Lymphoma
- Monoclonal Antibody
- CD30
- Antibody Saturation
- Apoptosis
- Flow Cytometry
- Cancer
- Neoplasms
Name | Location |
|---|---|
| National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda, Maryland 20892 |
| Beth Israel Deaconess Medical Center | Boston, Massachusetts 02215 |
