Clinical trial NCT01273090: Imetelstat Sodium in Treating Young Patients With Refractory or Recurrent Solid Tumors or Lymphoma
Official title: A Phase 1 Study of Imetelstat, a Telomerase Inhibitor, in Children With Refractory or Recurrent Solid Tumors and Lymphomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Brain and Central Nervous System Tumors
Lymphoma
Lymphoproliferative Disorder
Small Intestine Cancer
Unspecified Childhood Solid Tumor, Protocol Specific
Keywords: 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
recurrent childhood central nervous system embryonal tumor
childhood central nervous system choriocarcinoma
childhood central nervous system germ cell tumor
childhood central nervous system germinoma
childhood central nervous system mixed germ cell tumor
childhood central nervous system teratoma
childhood central nervous system yolk sac tumor
recurrent childhood pineoblastoma
childhood diffuse large cell lymphoma
childhood nasal type extranodal NK/T-cell lymphoma
childhood nodular lymphocyte predominant Hodgkin lymphoma
angioimmunoblastic T-cell lymphoma
childhood Burkitt lymphoma
childhood grade III lymphomatoid granulomatosis
childhood immunoblastic large cell lymphoma
cutaneous B-cell non-Hodgkin lymphoma
hepatosplenic T-cell lymphoma
intraocular lymphoma
noncutaneous extranodal lymphoma
peripheral T-cell lymphoma
post-transplant lymphoproliferative disorder
recurrent cutaneous T-cell non-Hodgkin lymphoma
recurrent mycosis fungoides/Sezary syndrome
small intestine lymphoma
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2011-01-10
Enrollment: 34
Sex: ALL
Minimum age (years): 1
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Maximum-tolerated dose and/or recommended phase II dose of imetelstat sodium in children with refractory or recurrent solid tumors or lymphoma
timeFrame: 21 Days
measure: Toxicities of imetelstat sodium
timeFrame: Up to 30 days post-treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Comprehensive Cancer Center
state: Alabama
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Atlanta
country: United States
facility: AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
state: Georgia
city: Chicago
country: United States
facility: Children's Memorial Hospital - Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Riley's Children Cancer Center at Riley Hospital for Children
state: Indiana
city: Bethesda
country: United States
facility: Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
state: Maryland
city: Boston
country: United States
facility: Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: C.S. Mott Children's Hospital at University of Michigan Medical Center
state: Michigan
city: St. Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
state: Missouri
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Portland
country: United States
facility: Knight Cancer Institute at Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Dallas
country: United States
facility: Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
state: Texas
city: Houston
country: United States
facility: Baylor University Medical Center - Houston
state: Texas
city: Seattle
country: United States
facility: Children's Hospital and Regional Medical Center - Seattle
state: Washington
city: Milwaukee
country: United States
facility: Midwest Children's Cancer Center at Children's Hospital of Wisconsin
state: Wisconsin
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: Hopital Sainte Justine
state: Quebec
Study officials:
affiliation: Baylor College of Medicine
name: Patrick A. Thompson, MD
role: PRINCIPAL_INVESTIGATOR
References: