Imetelstat for Children With Refractory or Recurrent Solid Tumors and Lymphoma

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01568632
First received: March 30, 2012
Last updated: November 20, 2012
Last verified: November 2012
  Purpose

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....

Condition Intervention Phase
Solid Tumors
Lymphoma
Drug: Imetelstat
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
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 National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • 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 Outcome Measures:
  • 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.

Enrollment: 0
Study Start Date: March 2012
Study Completion Date: October 2012
Intervention Details:
    Drug: Imetelstat
    N/A
  Show Detailed Description

  Eligibility

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

  1. Myelosuppressive chemotherapy: Must not have received

    myelosuppressive chemotherapy within 3 weeks of enrollment onto this study (6 weeks if prior nitrosourea).

  2. 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.
  3. 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.
  4. Immunotherapy: At least 6 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines.
  5. Monoclonal antibodies: At least 3 half-lives of the antibody after the last dose of a monoclonal antibody.
  6. 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.
  7. 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.

Organ Function Requirements

- Adequate Bone Marrow Function Defined as:

  1. For patients with solid tumors without known bone marrow involvement:

    - Peripheral absolute neutrophil count (ANC) : greater than or equal to 1000/mm(3)

    • Platelet count : greater than or equal to 100,000/mm(3) (transfusion independent, defined as not receiving platelet transfusions within a 7 day period priorto enrollment)
  2. Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts in

    -.a (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. At least 5 of every cohort of 6 patients with a solid tumor must be evaluable for hematologic toxicity. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity.

    - Adequate Renal Function Defined as:

    • Creatinine clearance or radioisotope GFR greater than or equal to 70ml/min/1.73 m(2) or
    • A serum creatinine based on age/gender as follows:

    Age Maximum Serum Creatinine (mg/dL)

    Male Female

    1 to < 2 years 0.6 0.6

    2 to < 6 years 0.8 0.8

    6 to < 10 years 1 1

    10 to < 13 years 1.2 1.2

    13 to < 16 years 1.5 1.4

    greater than or equal to 16 years1.7 1.4

    - Adequate Liver Function Defined as:

    - Bilirubin (sum of conjugated + unconjugated) less than or equal to 1.5 x upper limit of normal (ULN) for age

    - SGPT (ALT) less than or equal to 110 U/L. For the purpose of this study, the ULN for

    SGPT is 45 U/L.

    - Serum albumin greater than or equal to 2 g/dL

    Adequate Coagulation Defined as:

    - aPTT < 1.2 x ULN

    Informed Consent: All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.

    EXCLUSION CRITERIA:

    - 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.
  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: NCT01568632

Sponsors and Collaborators
Investigators
Principal Investigator: William L Dahut, M.D. National Cancer Institute (NCI)
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT01568632     History of Changes
Other Study ID Numbers: 120091, 12-C-0091
Study First Received: March 30, 2012
Last Updated: November 20, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Dose Limiting Toxicity
Maximum Tolerated Dose
Telomerase Inhibitor
Safety
Solid Tumor
Lymphoma

Additional relevant MeSH terms:
Lymphoma
Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on July 31, 2014