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| Sponsor: | National Cancer Institute (NCI) |
|---|---|
| Information provided by: | National Institutes of Health Clinical Center (CC) |
| ClinicalTrials.gov Identifier: | NCT00048880 |
Purpose
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:
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Neoplasms |
Drug: HeFi-1 Monoclonal Antibody |
Phase I |
| Study Type: | Interventional |
| Study Design: | Treatment |
| Official Title: | Phase I Study of HeFi-1 in Refractory CD30-Positive Malignancy |
| Estimated Enrollment: | 18 |
| Study Start Date: | November 2002 |
| Estimated Study Completion Date: | September 2005 |
The primary objective of this study is to determine the toxicity and maximum tolerated dose of HeFi-1 in patients with CD30 positive malignancy. Cohorts of three patients will be treated with escalating doses of HeFi-1 ranging from 0.5 to 5 mg/kg/dose (total dose of 2 to 20 mg/kg per treatment course). Treatment doses will be divided and given every three days for 10 days. This study will allow us to explore the pharmacokinectics and dose required to saturate CD30 binding sites in tumor aspirates, the frequency and time course of onset of development of human anti-mouse antibody (HAMA), and the fraction of CD30 positive cells that undergo ex-vivo apoptosis in response to HeFi-1. These studies will allow us to monitor the clinical tumor response, measured by reduction in tumor lesions and by following the tumor marker serum soluble interleukin 2 receptor, and to correlate response with the in vitro tumor apoptosis induction assay. This study represents an extension of Metabolism Branch basic research efforts towards understanding the mechanism of cytotoxicity of antibodies to CD30. The scientific basis for this study is the observation that antibodies directed at the ligand-binding site of CD30 induce apoptosis in vitro. The induction of apoptosis is correlated with CD30 ligation in the absence of NF-(kappa)B activation. 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(kappa)B kinase which result in constitutive activation of NF-(kappa)B. If beneficial tumor responses are observed with HeFi-1 infusion, efforts to pursue humanization of the antibody will be pursued and future studies using HeFi-1 in combination with chemotherapy based on in vitro synergism will be conducted. Treatment with HeFi-1 and agents that prevent NF-(kappa)B activation would be expected to have activity in patients with Hodgkin's disease.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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| Contact: NCI Referral Office | ncissc@mail.nih.gov | |
| Contact: CSSC | 8886241937 | ncicssc@mail.nih.gov |
| United States, Maryland | |
| National Cancer Institute (NCI) | Recruiting |
| Bethesda, Maryland, United States, 20892 | |
More Information
| Study ID Numbers: | 030038, 03-C-0038 |
| Study First Received: | November 8, 2002 |
| Last Updated: | June 19, 2006 |
| ClinicalTrials.gov Identifier: | NCT00048880 History of Changes |
| Health Authority: | United States: Federal Government |
|
Anaplastic Large Cell Lymphoma Monoclonal Antibody CD30 Antibody Saturation |
Apoptosis Flow Cytometry Cancer |
|
Antibodies, Monoclonal Antibodies Neoplasms |
Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions |
