A Phase 1 Study of Imetelstat, a Telomerase Inhibitor, in Children With Refractory or Recurrent Solid Tumors and Lymphomas

BACKGROUND:

• Telomerase is an enzyme that plays a critical role in maintaining telomeres, the specialized structures at the end of chromosomes involved in the replication and stability of the chromosome. Inhibition of telomeres causes the length of the telomere to shorten, and the cell becomes either senescent or undergoes apoptosis.
• In vitro and in vivo studies have demonstrated that imetelstat, a telomerase inhibitor, inhibits primary tumor growth and prevents metastases; while six Phase 1 studies in adults have demonstrated reasonable toxicity profiles with hematologic toxicity the primary cause of dose limiting toxicity.
• Objective responses have been observed with repeated dosing when imetelstat was administered in combination with bortezomib to patients with multiple myeloma, with paclitaxel and bevacizumab to patients with advanced breast cancer, and with paclitaxel plus carboplatin in patients with advanced NSCLC.

OBJECTIVES:

Primary Objectives:

• To estimate the maximum tolerated dose (MTD) and/or recommended Phase 2 dose of imetelstat administered as a 2-hour intravenous infusion, weekly X 2, every 21 days, to children with refractory or recurrent solid tumors.
• To define and describe the toxicities of imetelstat administered on this schedule.
• To characterize the pharmacokinetics of imetelstat in children with recurrent or refractory solid tumors.