Phase I Study of MEDI-507 to Treat Lymphoproliferative Disease
This study will determine how much MEDI-507 can be safely given to people with lymphoproliferative diseases - certain cancers that affect infection-fighting white blood cells called T cells. In most cancers that affect T cells, the cells have a protein on their surface called CD2. MEDI-507 is a genetically engineered antibody that targets CD2. In laboratory studies, MEDI-507 has shown some effect in animals with T-cell cancer.
Patients 18 years of age and older with adult T-cell leukemia/lymphoma, cutaneous T-cell lymphoma, peripheral T-cell lymphoma, or large granular lymphocyte leukemia who have CD2 protein on their T cells may be eligible for this study. Patients (except for those with adult T-cell leukemia/lymphoma) must have had prior treatment with chemotherapy, radiation therapy, or antibodies. Candidates are screened with a medical history and physical examination, blood and urine tests, electrocardiogram, x-rays and other imaging studies, photographs of skin lesions, if any, a skin biopsy (removal of a small piece of tissue) of suspicious lesions, and lymph node biopsy, if the node is accessible by a fine needle.
Patients are enrolled into one of seven groups, with three patients per group. Subsequent groups of patients receive a higher dose of MEDI-507 than the previous one as long as the drug continues to be safe and well tolerated. The first group of patients receives 0.2 milligrams mg/kg of the drug for 2 consecutive days every other week for 16 weeks. The next three patients entering the study receive the same dose for 3 consecutive days every other week. Subsequent groups receive higher doses of the antibody. Patients are hospitalized on the days they receive the antibody.
In addition to MEDI-507 treatment, patients may receive additional therapies as follows:
- Diphenhydramine (Benadryl(Registered Trademark)) and acetominophen (Tylenol(Registered Trademark)) to reduce allergic reactions to MEDI-507.
- Blood transfusions to maintain sufficient levels of blood cells and platelets.
- Filgrastim, a drug that stimulates production of white blood cells, to improve white cell counts.
- Allopurinol, a drug that helps help prevent tumor lysis syndrome. Cancer treatment may sometimes result in this condition, which upsets the way the body gets rid of certain chemicals in the blood. Allopurinol is taken by mouth for 5 days starting 1 day before each MEDI-507 infusion.
- Anti-infective agents, such as fluconazole, valacyclovir, trimethoprim-sulfamethoxazole, and others as needed to prevent bacterial, viral, or fungal infections.
After patients complete the 16-week course of treatment, they return to the clinic for follow-up examinations 30 days after the last drug dose and then every 3 months for 1 year.
|Study Design:||Primary Purpose: Treatment|
|Official Title:||Phase I Trial of Medi-507 in CD2-Positive Lymphoproliferative Disease|
|Study Start Date:||October 2003|
|Study Completion Date:||July 2008|
|Primary Completion Date:||July 2008 (Final data collection date for primary outcome measure)|
- Monclonal antibodies have significant therapeutic benefit in patients with cancer.
- MEDI-507 is an IgG1 humanized monoclonal antibody directed at CD2 which is highly expressed on malignant T and NK cells.
- NOD/SCID mice bearing CD2 positive MET-1 adult T-cell leukemia/lymphoma survive tumor challenge and have a survival equivalent to that of non-tumor bearing animals when treated with weekly doses of MEDI-507.
- Determine the maximum tolerated dose (MTD), safety and tolerability of MEDI-507 in patients with CD2-positive lymphoproliferative disorders.
- Evaluate the serum pharmacokinetics of MEDI-507 and determine the dose of MEDI-507 required to saturate CD2-binding sites in lymph nodes and peripheral blood.
- Assess the clinical tumor response in a preliminary fashion in a variety of CD2-positive lymphoproliferative disorders.
-Patients with CD2 positive lymphoproliferative disease including untreated patients with adult T-cell leukemia/lymphoma; patients with large granular lymphocyte leukemia, peripheral T-cell lymphoma and cutaneous T-cell lymphoma who have progressive disease after standard therapy.
- Cohorts of patients will be treated with escalating doses of MEDI-507 ranging from 0.4 to 15 mg/kg.
- Tumor response will be evaluated on a monthly basis during treatment.
- Tumor aspirates will be obtained before and after treatment to determine the effect of MEDI-507 on CD2 expression.
- The time course of T and NK cell depletion and recovery will be monitored.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Thomas A Waldmann, M.D.||National Cancer Institute (NCI)|