ADVL1112, A Phase 1 Study of Imetelstat, a Telomerase Inhibitor, in Children with Refractory or Recurrent Solid Tumors and Lymphomas

Summary

in this pediatric Phase i trial, imetelstat will be given intravenously over two hours on Days 1 and 8 every 21 days. The starting dose of imetelstat will be 225 mg/m2 (equivalent to 7.5 mg/kg), which is approximately 80% of the adult recommended dose. escalations in subsequent cohorts will occur in increments of approximately 30% using the rolling six design. There will be no intrapatient dose escalation. Pharmacokinetic samples will be obtained in all patients. Blood and tumor samples will be obtained for correlative biology to assess telomerase activity in consenting patients. Patients may receive a total of 18 cycles of therapy in the absence of progressive disease or unacceptable toxicity.

Participant Eligibility

Age: Patients must be > than 12 months and <= 21 years of age (<= 18 years of age at this institution) at the time of study enrollment.

Diagnosis: Patients with refractory or recurrent solid tumors, including
lymphomas, without CNS tumors or known CNS metastases are eligible for the
initial dose escalation phase (Part A). Once the MTD or recommended phase 2 dose has been defined, patients with CNS tumors or known CNS metastases may enroll in the expanded cohort (Part B). All patients must have had histologic verification of malignancy at original diagnosis or relapse except patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of CSF or serum tumor markers including alpha-fetoprotein or beta-HCG.

Disease Status: Patients must have either measurable or evaluable disease

Therapeutic Options: Patient[Single Quote]s current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life.

Performance Level: Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients <= 16 years of age.

Prior Therapy: Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy, immunotherapy, or radiotherapy.

Organ Function Requirements: Adequate bone marrow, renal, liver and cardiac function.

All patients and/or their parent or legal guardian must sign a written informed consent.

All institutional, FDA, and NCI requirements for human studies must be met.