Imetelstat Sodium in Treating Young Patients With Refractory or Recurrent Solid Tumors or Lymphoma

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT01273090
First received: January 7, 2011
Last updated: January 29, 2014
Last verified: January 2014
  Purpose

RATIONALE: Imetelstat sodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I clinical trial is studying the side effects and best dose of imetelstat sodium in treating young patients with refractory or recurrent solid tumors or lymphoma.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Lymphoma
Lymphoproliferative Disorder
Small Intestine Cancer
Unspecified Childhood Solid Tumor, Protocol Specific
Drug: imetelstat sodium
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study of Imetelstat, a Telomerase Inhibitor, in Children With Refractory or Recurrent Solid Tumors and Lymphomas

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Maximum-tolerated dose and/or recommended phase II dose of imetelstat sodium in children with refractory or recurrent solid tumors or lymphoma [ Time Frame: 21 Days ] [ Designated as safety issue: Yes ]
  • Toxicities of imetelstat sodium [ Time Frame: Up to 30 days post-treatment ] [ Designated as safety issue: Yes ]

Enrollment: 34
Study Start Date: May 2011
Study Completion Date: October 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Drug: imetelstat sodium Other: laboratory biomarker analysis Other: pharmacological study

Detailed Description:

OBJECTIVES:

Primary

  • To estimate the maximum-tolerated dose (MTD) and/or recommended phase II dose of imetelstat sodium in children with refractory or recurrent solid tumors or lymphoma.
  • To define and describe the toxicities of imetelstat sodium.
  • To characterize the pharmacokinetics of imetelstat sodium in children with refractory or recurrent solid tumors or lymphoma.

Secondary

  • To determine, in a preliminary manner, the antitumor effects of imetelstat sodium in children with refractory or recurrent solid tumors or lymphoma. (exploratory)
  • To provide preliminary assessment of the biological activity of imetelstat sodium in children with recurrent or refractory malignancies by assessing telomerase activity, telomere length, hTERT protein, hTERT mRNA, and hTR levels in patient peripheral blood mononuclear cells (PBMNC) samples pretreatment and on treatment. (Exploratory)
  • To assess telomerase activity, hTERT expression, telomere length, hTERT protein, hTERT mRNA, and hTR levels in patients' pretreatment tumor samples. (Exploratory)

OUTLINE: This is a multicenter, dose-escalation study.

Patients receive imetelstat sodium IV over 2 hours on days 1 and 8. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo blood sample collection at baseline and periodically during study for pharmacokinetic and correlative studies. Tumor tissue samples from diagnosis and/or subsequent tumor resections or biopsies may also be collected for correlative studies.

After completion of study therapy, patients are followed up for 30 days.

  Eligibility

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of refractory or recurrent solid tumors, including lymphoma

    • No CNS tumors or known CNS metastases (Part A, dose escalation)
    • CNS tumors or known CNS metastases allowed (Part B, maximum-tolerated dose or recommended phase II dose)

      • No prior or concurrent CNS hemorrhage on a baseline MRI within the past 14 days
    • All patients must have histologic verification of malignancy at original diagnosis or relapse except for:

      • Intrinsic brain stem tumors
      • Optic pathway gliomas
      • Pineal tumors and elevations of CSF or serum tumor markers including alpha-fetoprotein or beta-HCG
  • Measurable or evaluable disease
  • Disease for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
  • Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood count criteria and they are not known to be refractory to red cell or platelet transfusions

PATIENT CHARACTERISTICS:

  • Karnofsky performance status (PS) 50-100% (patients > 16 years of age) OR Lansky PS 50-100% (patients ≤ 16 years of age)
  • ANC ≥ 1,000/mm³
  • Platelet count ≥ 100,000/mm³ (transfusion-independent, defined as not receiving platelet transfusion within the past 7 days prior to enrollment)
  • Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR a serum creatinine based on age and/or gender as follows:

    • 0.6 mg/dL (1 to < 2 years of age)
    • 0.8 mg/dL (2 to < 6 years of age)
    • 1.0 mg/dL (6 to < 10 years of age)
    • 1.2 mg/dL (10 to < 13 years of age)
    • 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)
    • 1.7 mg/dL (male) or 1.4 mg/dL (female) (≥ 16 years of age)
  • Bilirubin (sum of conjugated and unconjugated) ≤ 1.5 times upper limit of normal (ULN)
  • ALT ≤ 110 U/L (ULN for ALT is 45 U/L)
  • Serum albumin ≥ 2 g/dL
  • aPTT < 1.2 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use an effective contraception method
  • No uncontrolled infection
  • No patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study

PRIOR CONCURRENT THERAPY:

  • Recovered from acute toxic effects of all prior anti-cancer chemotherapy, immunotherapy, or radiotherapy
  • At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosourea)
  • At least 14 days since prior long-acting growth factor (e.g., Neulasta) or ≥ 7 days since prior short-acting growth factor
  • At least 7 days since prior biologic or anti-neoplastic agent
  • At least 6 weeks since any type of prior immunotherapy (e.g., tumor vaccines)
  • At least 3 half-lives since last dose of a monoclonal antibody
  • At least 2 weeks since prior local palliative radiotherapy (small port)

    • At least 24 weeks since prior total-body irradiation, craniospinal radiotherapy, or radiation to ≥ 50% of the pelvis
    • At least 6 weeks since prior substantial bone marrow radiation
  • At least 12 weeks since prior transplantation or stem cell infusion with no evidence of active graft vs host disease
  • Prior and concurrent stable or decreasing dose of corticosteroids within the past 7 days allowed
  • No prior allogeneic transplant
  • No other concurrent investigational drug
  • No other concurrent anticancer agents including chemotherapy, radiotherapy, immunotherapy, or biologic therapy
  • No concurrent cyclosporine, tacrolimus, or other agents to prevent either graft-versus-host disease post-bone marrow transplant or organ rejection post-transplant
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01273090

  Show 23 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: Patrick A. Thompson, MD Baylor College of Medicine
  More Information

Additional Information:
No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT01273090     History of Changes
Other Study ID Numbers: ADVL1112, COG-ADVL1112
Study First Received: January 7, 2011
Last Updated: January 29, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Children's Oncology Group:
unspecified childhood solid tumor, protocol specific
recurrent childhood anaplastic large cell lymphoma
recurrent childhood grade III lymphomatoid granulomatosis
recurrent childhood large cell lymphoma
recurrent childhood lymphoblastic lymphoma
recurrent childhood small noncleaved cell lymphoma
recurrent/refractory childhood Hodgkin lymphoma
recurrent childhood brain stem glioma
recurrent childhood anaplastic astrocytoma
recurrent childhood anaplastic oligoastrocytoma
recurrent childhood anaplastic oligodendroglioma
recurrent childhood cerebellar astrocytoma
recurrent childhood cerebral astrocytoma
recurrent childhood diffuse astrocytoma
recurrent childhood fibrillary astrocytoma
recurrent childhood gemistocytic astrocytoma
recurrent childhood giant cell glioblastoma
recurrent childhood glioblastoma
recurrent childhood gliomatosis cerebri
recurrent childhood gliosarcoma
recurrent childhood oligoastrocytoma
recurrent childhood oligodendroglioma
recurrent childhood pilocytic astrocytoma
recurrent childhood pilomyxoid astrocytoma
recurrent childhood pleomorphic xanthoastrocytoma
recurrent childhood protoplasmic astrocytoma
recurrent childhood subependymal giant cell astrocytoma
recurrent childhood visual pathway and hypothalamic glioma
recurrent childhood visual pathway glioma
childhood pineal parenchymal tumor

Additional relevant MeSH terms:
Lymphoma
Lymphoproliferative Disorders
Nervous System Neoplasms
Central Nervous System Neoplasms
Duodenal Neoplasms
Ileal Neoplasms
Jejunal Neoplasms
Neoplasms
Intestinal Neoplasms
Neoplasms by Histologic Type
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms by Site
Nervous System Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Duodenal Diseases
Intestinal Diseases
Ileal Diseases
Jejunal Diseases

ClinicalTrials.gov processed this record on September 14, 2014