Imetelstat for Children With Refractory or Recurrent Solid Tumors and Lymphoma

Lymphoma Clinical Trial

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

Status Withdrawn

Clinical Trial Summary

Background:

• Imetelstat is a cancer treatment drug that may slow or stop tumor growth. It may also prevent tumors from spreading to other parts of the body. Researchers want to see if it can be a safe and effective treatment for children who have solid tumors or lymphoma that have not responded to other treatments.

Objectives:

• To see if imetelstat is a safe and effective treatment for children who have solid tumors or lymphoma that have not responded to other treatments.

Eligibility:

• Children and adolescents between 1 and 21 years of age who have solid tumors or lymphoma that have not responded to other treatments.

Design:

• Participants will be screened with a physical exam, medical history, and imaging studies. Blood and urine samples will also be collected.

• Participants will receive imetelstat on the first and eighth day of a 21-day cycle of treatment.

• Treatment will be monitored with frequent blood tests and imaging studies. Tumor biopsies may also be performed.

• Participants will keep taking the study drugs for up to a total of 18 cycles as long as the disease does not progress and there are no severe side effects....

Clinical Trial Description

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.

Secondary Objectives:

• To preliminarily define antitumor effects of imetelstat and to assess the biological activity by assessing telomerase activity, telomere length, hTERT protein, hTERT mRNA and hTR levels in patient PBMNC samples pretreatment and while on treatment, and assess telomerase activity, hTERT expression and hTERT protein, telomere length, hTERT mRNA and hTR levels in patient's pretreatment tumor samples.

ELIGIBILITY:

• Patients > 12 months and less than or equal to 21 years of age with recurrent or refractory solid tumors, including lymphomas, without CNS tumors or known CNS metastases, and with adequate hematologic, hepatic, renal and cardiac status. Must meet safety laboratory testing levels.

DESIGN:

• In this phase I study, the maximum tolerated dose of imetelstat will be determined using a rolling 6 design where a minimum of 2 evaluable patients will be entered at each of 4 dose levels, where imetelstat is administered intravenously over two hours on Day 1 and 8 of a 21-day cycle in children with recurrent or refractory solid tumors, for up to 17 cycles, up to a total duration of therapy of 18 cycles (approximately 12 months).

• Premedication with acetaminophen and diphenhydramine will be administered prior to each dose; anaphylactic precautions should be adhered to, and steroids may be used for symptom control or as premedication after the first dose. Doses subsequent to the first dose may be delayed or withheld for toxicity.

This study will include a required pharmacokinetic component, and one optional PK draw at 48 hours after the first dose (Day 1, Cycle 1). Patients will be asked to participate in optional blood and tissue correlative biology studies. Radiology studies will undergo central radiology review.

• Once MTD has been defined, up to 12 additional patients with relapsed/refractory solid tumors, including

CNS tumors and lymphomas, may be enrolled to acquire additional PK data at the recommended phase 2 dose, attempting to enroll at least 6 patients < 12 years of age. With a maximum number of patients of

45, this study is anticipated to be completed within 22 to 25 months. Up to 5 patients will be enrolled at NCI. ;

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Solid Tumors

• NCT number: NCT01568632
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Withdrawn
• Phase: Phase 1
• Start date: March 2012
• Completion date: October 2012