Phase I/II Trial of Ceritinib with Brentuximab Vedotin in Treatment-Naive ALK-Positive Anaplastic Large Cell Lymphoma: Safety, Dosage, and Efficacy

This phase I/II trial studies the side effects and best dose of ceritinib when given together with brentuximab vedotin to see how well they work in treating treatment-naive patients with anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma. Ceritinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as brentuximab vedotin, may interfere with the ability of tumor cells to grow and spread. Giving ceritinib together with brentuximab vedotin may be a better treatment for ALK-positive anaplastic large cell lymphoma.

Detailed Description

PRIMARY OBJECTIVES: I. To define a dose of ceritinib administered concurrently with brentuximab vedotin that has an acceptable toxicity profile (based on dose-limiting toxicity [DLT] rate) and sufficient efficacy (based on response rate) among patients with treatment-naive ALK-positive anaplastic large cell lymphoma (ALCL). SECONDARY OBJECTIVES: I. To assess the antitumor activity of ceritinib and brentuximab vedotin combination in treatment-naive patients with ALK-positive ALCL. II. To assess the utility of the molecular marker of ALK-positive ALCL in patient’s plasma before, during and after therapy for disease risk assessment and post-treatment monitoring. OUTLINE: This is a phase I, dose-escalation study of ceritinib followed by a phase II study. Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1. Patients also receive ceritinib orally (PO) once daily (QD) on days 8–21 of course 1 and on days 1–21 for all subsequent courses. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months up to 3 years.