Clinical Trial: Ruxolitinib in the Treatment of Chronic Lymphocytic Leukemia

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase I/II Trial of Ruxolitinib (Jakafi) in Patients With Chronic Lymphocytic Leukemia Who Are Unfit for Conventional First-line Therapy Due to Age or 17p Deletions

Brief Summary: The purpose of this study is to determine if Ruxolitinib, an inhibitor of cytokine-signaling, is effective in the treatment of patients with Chronic Lymphocytic Leukemia for whom conventional chemotherapy is either too toxic or ineffective.

Detailed Summary:

Chronic lymphocytic leukemia (CLL) is the commonest leukemia in adults and, until recently, had limited treatment options. However, the combination of fludarabine, cyclophosphamide, and rituximab (FCR) produces impressive clinical responses and prolongs survival of many CLL patients with symptomatic disease. Unfortunately, FCR is a toxic regimen that cannot generally be tolerated by patients over the age of 65 years who constitute more than 70% of the CLL patient population. In addition, FCR is contraindicated in patients whose leukemia cells harbor deletions of chromosome 17, where the tumor suppressor p53 is located, because such cells are intrinsically resistant to genotoxic drugs. This group constitutes 10-15% of patients of all ages who require first-line therapy. Better therapies for these two large groups of patients are needed.

The initiating event in CLL is thought to be genetic damage to a class of B lymphocytes that prevents proper functioning of apoptotic pathways. However, disease progression is driven by signals from the proliferation centers in tumor microenvironments where circulating CLL cells originate. Signals that cause CLL cells to proliferate include antigens that activate B-cell receptors (BCRs), Toll-like receptor ligands, chemokines, and cytokines. CLL cells that respond strongly to these microenvironmental signals exhibit more aggressive clinical behavior and resistance to cytotoxic drugs. These observations have motivated the use of signal transduction inhibitors to treat CLL and initial results of targeting kinases in the BCR-signaling cascade, such as Bruton's Tyrosine Kinase (BTK), suggest this strategy is effective and likely to change the treatment paradigm for CLL.

BCR signaling is not the only driver of CLL proliferation in vivo. Cytokines and chemokines in the tumor microenvironment activ
Sponsor: Sunnybrook Health Sciences Centre

Current Primary Outcome: Clinical response rate [ Time Frame: at 7 months ]

Original Primary Outcome: Same as current

Current Secondary Outcome: number of patients with adverse events [ Time Frame: participants will be followed for an average of 8 months ]

Original Secondary Outcome: Same as current

Information By: Sunnybrook Health Sciences Centre

Dates:
Date Received: December 3, 2013
Date Started: April 2014
Date Completion:
Last Updated: September 23, 2016
Last Verified: September 2016