Feasibility/Phase II Trial of Fludarabine, Rituximab, and Alemtuzumab for Previously Treated B-Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)
Immunotherapy, or treatments that work by boosting immune function in the body, such as
monoclonal antibodies have shown some efficacy against different types of leukemia.
Researchers have learned to manufacture antibodies outside of the human body that can bind
to specific targets in cancer cells. Monoclonal antibodies are designed to recognize
different proteins on specific cancer cells. The current study combines two monoclonal
antibodies, rituximab and fludarabine. Rituximab attaches to a protein called the CD20
antigen that is found almost exclusively on the surface of B-cells with leukemia. Once
rituximab attaches to the protein, the immune system activates to kill the malignant
B-cells. Alemtuzumab works in a similar way by attaching with the CD25 antigen and also has
activity in patients with p53 gene mutations. Previous studies indicate that both rituximab
and alemtuzumab separately have some efficacy against lymphocytic leukemia. Research has
also shown that fludarabine works against the disease. Rituximab and fludarabine in
combination appear to have a high response rate in patients. Researchers are seeking to
improve efficacy data by adding alemtuzumab to the combination of rituximab and fludarabine
in this study.
This study will evaluate the safety and efficacy of fludarabine, rituximab, and alemtuzumab
in patients with previously treated B-cell lymphocytic leukemia and small lymphocytic
leukemia. Blood and bone marrow tests will assess genetic features associated with response
to therapy, immune recovery, mechanisms of alemtuzumab's signaling, routes of drug
resistance, and traces of residual disease following complete response in patients.
Patients in this study will receive fludarabine, rituximab, and alemtuzumab. These drugs
will be administered through intravenous infusions. The treatment period will last 22 weeks.
Fludarabine will not be given during week one, 5 days during week 2, and 5 days during weeks
6, 10, 14, 18, and 22. Rituximab will not be given during week one, 3 times the second week,
and day one of weeks 6, 10, 14, 18, and 22. Alemtuzumab will be given 3 times during week
one, once during week 2, and day 2 of weeks 6, 10, 14, 18, and 22. The dosage amount of
rituximab and alemtuzumab will be increased depending upon the degree of side effects.
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.
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Assess the rate of complete (CR) and overall response (ORR) using fludarabine, rituximab, and alemtuzumab
John C. Byrd, M.D.
Ohio State University
United States: Institutional Review Board
|Ohio State University||Columbus, Ohio 43210|