Protocol Number: 03-C-0038

Title:

Phase I Study of HeFi-1 in Refractory CD30-Positive Malignancy

Number:

03-C-0038

Summary:

This study will determine the highest dose of HeFi-1 that can safely be given to patients with cancers that have a protein called CD30 on their tumor cells. HeFi-1 is an antibody that binds to CD30 and sends signals to the cancer cells that can cause them to die.

Patients with Hodgkin's disease, anaplastic large cell lymphoma, cutaneous T cell lymphoma, and adult T cell leukemia or lymphoma may be eligible for this study. Candidates must have signs of tumor growth or recurrence following standard treatment, and their tumor cells must have a protein called CD30. Patients with early-stage disease, smoldering adult T cell leukemia, or limited patches of skin involvement may not enroll. Candidates will be screened with a medical history, physical examination, blood and urine tests, electrocardiogram (ECG), and imaging studies, including chest X-ray and CT scans, and possible skin biopsy. Skin lesions will be photographed. (See below for information on biopsies.)

Participants will receive four 30-minute infusions of HeFi-1 intravenously (through a vein) in 28-day treatment cycles. The infusions will be given on days 0 (first day of the cycle), 3, 6, and 9 of each cycle. The 2-day period between infusions may be extended if drug side effects occur. The first dose will be given in the hospital. Subsequent doses will be given on an outpatient basis if no significant side effects develop after the first infusion. The drug dose will be increased in successive groups of three patients each, for a total of five different doses. Each dose will be two times higher than the previous one, except for the last dose, which will be 50 percent higher than that for the preceding group. Patients may continue treatment as long as their tumor is not growing and they do not develop antibodies to HeFi-1 or serious treatment side effects. In addition to the drug treatment, patients will undergo the following tests and procedures:

- Blood draws. Blood samples will be collected several times to determine the safety of the treatment.

- Lymph node biopsies or aspirates. Up to three biopsies or aspirates will be taken during the first treatment cycle to examine the effect of HeFi-1 on tumor cells.

- Bone marrow biopsy before, and possibly after, treatment. For this test, the area of the hip is anesthetized and a special needle is used to draw bone marrow from the hipbone.

A biopsy takes a piece of tissue or tumor to examine it under the microscope. Biopsies may be done with a large needle, called a needle biopsy, with a small sharp cookie-cutter instrument, called a punch biopsy, or with a small knife, called an excisional biopsy. The procedure is similar for each of these. After the skin is cleaned thoroughly, a small amount of numbing medicine is given as a shot into the skin around the biopsy site. Then, if a needle biopsy is being done, a needle is put through the skin into the tumor to pull out a small piece of tumor in the length of the needle. If a punch biopsy is being done, a cookie cutter-like instrument is pushed into the numbed skin, and a small piece of tissue is removed. If an excisional biopsy is required, depending on the location to be biopsied, this may be done in the operating room or the clinic. The tissue is removed by cutting a small piece of tumor with a sharp knife or scalpel.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility 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.

Special Instructions: Currently Not Provided

Keywords:

Anaplastic Large Cell Lymphoma

Monoclonal Antibody

CD30

Antibody Saturation

Apoptosis

Flow Cytometry

Recruitment Keywords:

Cancer

Conditions:

Neoplasms

Investigational Drug(s):

HeFi-1 Monoclonal Antibody

Investigational Device(s):

None

Contacts:

CSSC
Clinical Studies Support Center/NCI
164 Rollins Avenue
2nd FLoor
Rockville, MD 20852
Phone: (888) 624-1937
Fax: (301) 881-8239

Electronic Address: ncicssc@mail.nih.gov

Citations:

Catane R, Longo DL. Monoclonal antibodies for cancer therapy.

Isr J Med Sci. 1988 Sep-Oct;24(9-10):471-6. Review.

Grillo-Lopez AJ, White CA, Varns C, Shen D, Wei A, McClure A, Dallaire BK. Overview of the clinical development of rituximab: first monoclonal antibody approved for the treatment of lymphoma. Semin Oncol. 1999 Oct;26(5 Suppl 14):66-73. Review.

Shak S. Overview of the trastuzumab (Herceptin) anti-HER2 monoclonal antibody clinical program in HER2-overexpressing metastatic breast cancer. Herceptin Multinational Investigator Study Group. Semin Oncol. 1999 Aug;26(4 Suppl 12):71-7. Review.

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