Clinical Trial: Ceritinib With Brentuximab Vedotin in Treating Patients With ALK-Positive Anaplastic Large Cell Lymphoma

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: A Phase I/II Open-Label Dose-Finding Study of Ceritinib Combined With Brentuximab Vedotin for Front-Line Treatment of ALK-Positive Anaplastic Large Cell Lymphoma

Brief Summary: 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 Summary:

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 anaplastic large cell lymphoma (ALCL), ALK-positive.

SECONDARY OBJECTIVES:

I. To assess the antitumor activity of ceritinib and brentuximab vedotin combination in treatment-naive patients with ALCL, ALK-positive.

II. To assess the utility of the molecular marker of ALCL, ALK-positive 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.


Sponsor: University of Washington

Current Primary Outcome:

  • Complete remission rate defined as the proportion of patients with CR according to the revised Response Criteria for Malignant Lymphoma [ Time Frame: Up to 3 years ]
  • Maximum tolerated dose (MTD) of ceritinib and brentuximab vedotin based on incidence of DLT assessed by NCI CTCAE version 4.03 [ Time Frame: Up to 6 weeks ]
  • Objective response rate defined as the proportion of patients with complete response (CR) or partial response (PR) according to the revised Response Criteria for Malignant Lymphoma [ Time Frame: Up to 3 years ]
    Assessed using clinical assessment and CT/PET scans


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Incidence of adverse events as assessed by NCI CTCAE version 4.03 [ Time Frame: Up to 30 days ]
  • Laboratory abnormalities as assessed by NCI CTCAE version 4.03 [ Time Frame: Up to 3 years ]
  • Overall survival (OS) defined as the time from start of study treatment to date of death due to any cause [ Time Frame: Up to 3 years ]
  • Progression-free survival (PFS) defined as the time from start of treatment to first documentation of objective tumor progression or to death due to any cause, whichever comes first [ Time Frame: Up to 3 years ]
    Evaluate tumor lesion size in the determination of PFS by using Revised Response Criteria for Malignant Lymphoma (modified Cheson, 2011)


Original Secondary Outcome: Same as current

Information By: University of Washington

Dates:
Date Received: March 29, 2016
Date Started: June 2017
Date Completion:
Last Updated: March 27, 2017
Last Verified: March 2017