Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Phase I Study of HeFi-1 to Treat Cancers With CD30 Protein

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00048880
First received: November 8, 2002
Last updated: March 6, 2010
Last verified: March 2010
  Purpose

Background:

  • Some cancers, such as Hodgkin's disease, anaplastic large cell lymphoma and others, have a protein on the surface of the cancer cell called CD30.
  • HeFi-1 is an antibody that binds to the CD30 protein and sends signals to the cancer cells that can cause them to die.

Objectives:

  • To determine the highest dose of HeFi-1 that can safely be given to patients with tumors that have the CD30 protein.
  • To determine the response of the tumor to treatment with HeFi-1.

Eligibility:

  • Patients 18 years of age and older with Hodgkin's disease, anaplastic large cell lymphoma, cutaneous T cell lymphoma and adult T cell leukemia or lymphoma who have signs of tumor growth or recurrence following standard treatment
  • Patients' tumor cells must have the CD30 protein.

Design:

  • Groups of three patients are treated with increasingly higher doses of HeFi-1 (ranging from 0.5 to 5 mg/kg) to determine the highest safe dose.
  • HeFi-1 is infused through a vein on 4 days, followed by 2 days of rest over a 10-day period. Patients may receive up to 2 treatment courses if they show some response and do not have severe side effects.
  • Blood samples are collected several times during the study to determine safety. A lymph node biopsy is done at the beginning of the study to test the effect of HeFi-1 on cancer cells in the test tube, and a bone marrow biopsy may be done at the end of treatment if the bone marrow was positive for tumor cells at the beginning of treatment.

Condition Intervention Phase
Neoplasms
Drug: HeFi-1 Monoclonal Antibody
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Phase I Study of HeFi-1 in Refractory CD30-Positive Malignancy

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Enrollment: 9
Study Start Date: November 2002
Study Completion Date: July 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: HeFi-1 Monoclonal Antibody
    N/A
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00048880

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00048880     History of Changes
Obsolete Identifiers: NCT00053079
Other Study ID Numbers: 030038, 03-C-0038
Study First Received: November 8, 2002
Last Updated: March 6, 2010
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Anaplastic Large Cell Lymphoma
Monoclonal Antibody
CD30
Antibody Saturation
Apoptosis
Flow Cytometry
Cancer

Additional relevant MeSH terms:
Antibodies
Antibodies, Monoclonal
Immunoglobulins
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2014