Alemtuzumab and CHOP Chemotherapy for Aggressive Histological Peripheral T-Cell Lymphomas

Aggressive peripheral T-cell lymphomas account for 10 - 15% of all Non-Hodgkin's Lymphoma (NHL) and present with more adverse prognostic features than aggressive histology B-cell NHL . Correspondingly, they have an overall poorer prognosis than B-cell lymphomas, achieving lower complete response rates, freedom from progression and overall survival with conventional anthracycline-based CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy. Fewer than 30% of patients are cured with therapy. New treatments that replicate the improved survivals with chemo-immunotherapy for B-cell lymphomas are needed. Alemtuzumab is a humanized murine antibody that binds to a ubiquitous lymphoid marker CD52 and is efficacious (as monotherapy) in related lymphoproliferative diseases. Combining alemtuzumab with CHOP chemotherapy may improve the response rates and outcomes of patients with this sub-type of NHL. The combination must be first tested in a dose escalation fashion to establish the dosage of the doublet because of the potential for overlapping or exaggerated toxicities. This prospective, multi-center, open label Phase I-II study will enroll 22-84 patients with newly diagnosed previously untreated aggressive histology peripheral T-cell lymphomas. In the Phase I component, patients will be sequentially enrolled in cohorts of three patients and treated with increasing doses of alemtuzumab administered in combination with standard CHOP chemotherapy. When the maximal tolerated dose is determined, this dose and schedule will then be tested in up to 46 patients using a Simon two stage Phase II design.