Imetelstat for Children With Refractory or Recurrent Solid Tumors and Lymphoma

NCT01568632 | Withdrawn Phase 1

• 2 other identifiers: 12009112-C-0091
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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....

Conditions

Solid Tumors; Lymphoma

Keywords

Dose Limiting Toxicity; Maximum Tolerated Dose; Telomerase Inhibitor; Safety; Solid Tumor; Lymphoma

Outcome Measures

Primary Outcomes (2)

• Estimate the maximum tolerated dose (MTD) of imetelstat given as a 2-hour IV infusion on D1 and D8 every 21 days.

• Define the toxicities and characterize pharmacokinetics

Secondary Outcomes (1)

• To define antitumor effects and to assess the biological activity by assessing telomerase activity, telomere length, hTERT protein, hTERT mRNA and hTR levels; hTERT expression and protein, telomere length, hTERT mRNAS and hTR levels in tumor.

Interventions

Imetelstat DRUG

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age: Patients must be \> than 12 months and less than or equal to 21 years of age 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 alphafetoprotein or beta-HCG.
• Disease Status: Patients must have either measurable or evaluable disease
• Therapeutic Options: Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with anacceptable quality of life.
• Performance Level: Karnofsky greater than or equal to 50% for patients \> 16 years of age and Lansky greater than or equal to 50 for patients less than 16 years of age. Note: Neurologic deficits in patients with CNS tumors must have been relatively stable for a minimum of 1 week prior to study enrollment. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Prior Therapy
• \- Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy, immunotherapy, or radiotherapy.
• Myelosuppressive chemotherapy: Must not have received
• myelosuppressive chemotherapy within 3 weeks of enrollment onto this study (6 weeks if prior nitrosourea).
• Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair.
• Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair.
• Immunotherapy: At least 6 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines.
• Monoclonal antibodies: At least 3 half-lives of the antibody after the last dose of a monoclonal antibody.
• XRT: greater than or equal to 2 weeks for local palliative XRT (small port); : greater than or equal to 24 weeks must have elapsed if prior TBI, craniospinal XRT or if : greater than or equal to 50% radiation of pelvis; greater than or equal to 6 weeks must have elapsed if other substantial BM radiation.
• Stem Cell Infusion without TBI: No evidence of active graft vs. host disease and : greater than or equal to 12 weeks must have elapsed since transplant or stem cell infusion. Patients with prior allogeneic transplants are not eligible.

You may not qualify if:

• \- Pregnancy or Breast-Feeding
• Pregnant or breast-feeding women will not be entered on this study, because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
• Concomitant Medications
• \- Corticosteroids: Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the prior 7 days are not eligible.
• \- Investigational Drugs: Patients who are currently receiving another investigational drug are not eligible.
• \- Anti-cancer Agents: Patients who are currently receiving other anticancer agents are not eligible.
• \- Anti-GVHD or agents to prevent organ rejection post-transplant:
• Patients who are receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post transplant are not eligible for this trial.
• Infection: Patients who have an uncontrolled infection are not eligible.
• Prior or current CNS bleed (Part B): Patients with CNS tumors or known CNS metastases who have imaging evidence of a prior or current CNS hemorrhage on the baseline MRI obtained within 14 days prior to study enrollment are not eligible. Note: The presence of small punctate areas consistent with hemorrhage on ECHO gradient MRI sequences will not exclude patients from participation.
• Patients with prior allogeneic transplants are not eligible.
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Related Publications (3)

• Harley CB, Futcher AB, Greider CW. Telomeres shorten during ageing of human fibroblasts. Nature. 1990 May 31;345(6274):458-60. doi: 10.1038/345458a0.

  PMID: 2342578 BACKGROUND

• Harley CB. Telomerase is not an oncogene. Oncogene. 2002 Jan 21;21(4):494-502. doi: 10.1038/sj.onc.1205076.

  PMID: 11850774 BACKGROUND

• Bosoy D, Peng Y, Mian IS, Lue NF. Conserved N-terminal motifs of telomerase reverse transcriptase required for ribonucleoprotein assembly in vivo. J Biol Chem. 2003 Feb 7;278(6):3882-90. doi: 10.1074/jbc.M210645200. Epub 2002 Nov 27.

  PMID: 12458198 BACKGROUND

MeSH Terms

Conditions

Lymphoma

Interventions

imetelstat

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• William L Dahut, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH

Study Record Dates

• First Submitted: March 30, 2012
• First Posted: April 2, 2012
• Study Start: March 1, 2012
• Study Completion: October 1, 2012
• Last Updated: November 21, 2012

Record last verified: 2012-11