Primary Outcome Measures:
- Maximum tolerated dose [ Time Frame: Every 3 weeks ] [ Designated as safety issue: Yes ]
- Adverse events [ Time Frame: Every 3 weeks ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- Pharmacokinetics [ Time Frame: Week 1 and Week 8 ] [ Designated as safety issue: No ]
Intervention Details:
Drug: Cyclophosphamide
750 mg/m2 IV on Day 1 every 3 weeks x 8.
Drug: Doxorubicin
50 mg/m2 IV on Day 1 every 3 weeks x 8.
Drug: Vincristine
1.4 mg/m2 (maximum dose = 2 mg) IV on Day 1 every 3 weeks x 8.
Drug: Prednisone
100 mg orally on Days 1-5 every 3 weeks x 8.
Drug: Alemtuzumab
Cohort 1 = 3 mg SQ Day 1 every 3 weeks x 8. Cohort 2 = 10 mg SQ Day 1 every 3 weeks x 8. Cohort 3 = 20 mg SQ Day 1 every 3 weeks x 8. Cohort 4 = 30 mg SQ Day 1 every 3 weeks x 8.
Rationale: The drug combination called CHOP, or Cyclophosphamide (Cytoxan), Doxorubicin (Adriamycin), Vincristine (Oncovin), and Prednisone (Deltasone), has been used against different types of lymphoma for many years. Researchers are investigating what other therapies to combine with the CHOP regimen to improve outcomes for patients with lymphoma. The current study combines CHOP with alemtuzumab, a monoclonal antibody used against leukemia. Monoclonal antibodies are a type of immunotherapy used against some types of cancer. They are produced in a laboratory and designed to target as well as bind with cells that carry specific proteins. Alemtuzumab is designed to target leukemia cells that express a specific protein. The specific protein recognized by alemtuzumab is the CD52 antigen. This antigen, or substance that causes the immune system to create a specific response, is expressed on normal B and T cells, as well as on abnormal T cells characteristic of certain cancers. Alemtuzumab causes the CD52 antigen to bind with B-cell lymphocytes. This study will also assess the theory that alemtuzumab may increase the effectiveness of the chemotherapy agents included in the CHOP regimen.
Treatment: Patients in this study will receive alemtuzumab and CHOP. Alemtuzumab will be given through injections into the skin and CHOP will be administered through intravenous infusions. Patients will receive alemtuzumab alone during the first week of the study. An increasing amount of alemtuzumab will be given during the first week. If patients cannot tolerate the highest amount of alemtuzumab determined as appropriate within one week, they will be removed from the study. Once the highest dose of alemtuzumab has been achieved, patients will then receive both alemtuzumab and CHOP every three weeks. This schedule will be repeated up to eight times. Several tests and exams will be given throughout the study to closely monitor patients. Treatments will be discontinued due to disease growth or unacceptable side effects.
Purpose
