Open Label Study to Evaluate the Activity of Imetelstat in Patients With Essential Thrombocythemia or Polycythemia Vera (ET/PV)

This study has suspended participant recruitment.
(Investigational New Drug (IND) application for imetelstat has been placed on full clinical hold)
Sponsor:
Information provided by (Responsible Party):
Geron Corporation
ClinicalTrials.gov Identifier:
NCT01243073
First received: November 11, 2010
Last updated: March 24, 2014
Last verified: March 2014
  Purpose

This is a phase II open-label study of single agent imetelstat in patients with essential thrombocytopenia or with polycythemia vera who have failed or are intolerant to at least one prior therapy, or who refuse standard therapy.


Condition Intervention Phase
Essential Thrombocythemia
Polycythemia Vera
Drug: Standard of Care
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial to Evaluate the Activity of Imetelstat (GRN163L) in Patients With Essential Thrombocythemia or Polycythemia Vera Who Require Cytoreduction and Have Failed or Are Intolerant to Previous Therapy, or Who Refuse Standard Therapy

Resource links provided by NLM:


Further study details as provided by Geron Corporation:

Primary Outcome Measures:
  • Hematologic Response [ Time Frame: From time of first dose (cycle 1 day 1) through end of study (12 mos after last participant is dosed) ] [ Designated as safety issue: No ]
    Primary objectives are as follows: ET patients - best hematologic response within the first year of therapy and PV patients - maintenance of Hct < 45% in men and < 42% in women (or pre-specified Hct count that is tolerable) without phlebotomy or myelosuppressive therapy within the first year of therapy. Secondary objectives, to determine the durability of hematologic response and to determine the rate of phlebotomy required within the first year of therapy.


Secondary Outcome Measures:
  • Safety and tolerability: Number of Patients with Hematological Toxicities, Non-Heme Grade 3 and 4 AEs, and Hemorrhagic Events [ Time Frame: From time of first dose (cycle 1 day 1) through end of study (12 mos after last paricipant is dosed) ] [ Designated as safety issue: Yes ]
    The safety and tolerability of imtelstat will be assessed by the incidence, nature, relatedness and severity of adverse events, laboratory abnormalities and vital signs.


Estimated Enrollment: 40
Study Start Date: December 2010
Estimated Study Completion Date: January 2016
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: imetelstat
Induction dosing of 9.4 mg/kg weekly, followed by intermittent maintenance dosing.
Drug: Standard of Care
Standard of care

Detailed Description:

For patients with ET: To obtain a preliminary estimate of efficacy of imetelstat, as measured by best hematologic response within the first year of therapy in patients with ET who have failed or are intolerant to at least one prior therapy, or who have refused standard therapy.

For patients with PV: To obtain a preliminary estimate of efficacy of imetelstat, as measured by maintenance of Hct < 45% in men and < 42% in women (or pre-specified Hct count that is tolerable) without phlebotomy or myelosuppressive therapy within the first year of therapy in patients with PV who have failed or are intolerant to at least one prior therapy, or who have refused standard therapy.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

ET-Specific Criteria

  • Confirmed diagnosis of ET by WHO criteria
  • Patients with ET requiring cytoreduction who have failed or are intolerant to at least one prior therapy, or who refuse standard therapy
  • Laboratory criteria (within 14 days of first study drug administration):

    • Platelets > 600,000/μL
    • ANC ≥ 1500/μL
    • Hemoglobin ≥ 10 g/dL

PV-Specific Criteria

  • Confirmed diagnosis of PV by WHO criteria
  • Patients with PV requiring cytoreduction with phlebotomy and/or myelosuppressive agents

    • Patients may have failed or are intolerant to at least one prior therapy, or refuse standard therapy
    • For those patients receiving phlebotomy only, the frequency over the past year must be at least one phlebotomy every 3 months.
  • Undergone phlebotomy and attained a Hct < 47% (men) or < 45% (women) (or pre-specified Hct count that is tolerable) within 14 days prior to the start of study treatment
  • Cessation of myelosuppressive agents prior to initiation of study treatment (unless approved by Geron Medical Monitor for unusual circumstances)

    • Hydroxyurea or anagrelide: Cessation 1 day prior to initiation of study treatment. Consideration to the timing of cessation of this therapy prior to the start of study treatment should take into account the requirement for phlebotomy.
    • INF-α or pegylated- INF-α: Cessation 4 weeks prior to initiation of study treatment
  • Laboratory criteria (within 14 days of first study drug administration):

    • Platelets > the lower limit of normal (LLN)
    • ANC ≥ 1500/μL

General Criteria (All Patients)

  • Willing and able to sign an informed consent
  • Male or female, aged 18 years or older
  • ECOG performance status 0-2
  • Laboratory criteria (within 14 days of first study drug administration):

    • INR (or PT) and aPTT < 1.5 x the upper limit of normal (ULN)
    • Serum creatinine ≤ 2 mg/dL
    • Serum bilirubin < 2.0 mg/dL (patients with Gilbert's syndrome: serum bilirubin < 3 x ULN)
    • AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN
    • Alkaline phosphatase < 2.5 x ULN
  • Any clinically significant toxicity from previous cancer treatments and/or major surgery must have recovered to Grade 0-1 prior to initiation of study treatment
  • Women of childbearing potential must have a negative pregnancy test and agree to use effective birth control during and for at least 12 weeks after the last study treatment with imetelstat
  • Male patients must agree to use effective birth control for themselves or their partner during and for 12 weeks after the last study treatment with imetelstat.

Exclusion Criteria

Patients who meet any of the following criteria will be excluded from screening and study entry:

  • Women who are pregnant or breast feeding
  • Prior stem cell transplantation
  • Investigational therapy within 4 weeks prior to first study drug administration
  • Clinically significant cardiovascular disease or condition including:

    • Uncontrolled congestive heart failure (CHF)
    • Need for anti-arrhythmic therapy for a ventricular arrhythmia
    • Clinically significant severe conduction disturbance per the Investigator's discretion
    • Ongoing angina pectoris requiring therapy
    • New York Heart Association (NYHA) Class II, III, or IV cardiovascular disease (see Appendix E)
  • Known positive serology for human immunodeficiency virus (HIV)
  • Serious co-morbid medical conditions, including active or chronically recurrent bleeding, clinically relevant active infection, cirrhosis, and chronic obstructive or chronic restrictive pulmonary disease per the Investigator's discretion
  • Any other severe, acute, or chronic medical or psychiatric condition, laboratory abnormality, or difficulty complying with protocol requirements that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for this study.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01243073

Locations
United States, California
City of Hope
Duarte, California, United States, 91010
United States, Florida
MDACC - Orlando
Orlando, Florida, United States, 32806
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Maryland
Johns Hopkins University - Bunting Blaustein Cancer Research Building
Baltimore, Maryland, United States, 21205
United States, South Carolina
Saint Francis Hospital
Greenville, South Carolina, United States, 29601
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Germany
University Hospital of Essen - West German Cancer Center
Essen, Germany
Medizinische Klinik II, Abt. Hämatologie und Onkologie - Johann Wolfgang Goethe Universität
Frankfurt, Germany, D-60590
SLK-Kliniken GmbH
Heilbronn, Germany
Hematology Oncology Center - Ludwig-Maximilians, University Munich Medical School
Munich, Germany, 80331
University Hospital Regensburg - Uniklinik Regensburg
Regensburg, Germany
Switzerland
INSELSPITAL, University Hospital Bern
Bern, Switzerland, CH - 3010
Sponsors and Collaborators
Geron Corporation
  More Information

No publications provided

Responsible Party: Geron Corporation
ClinicalTrials.gov Identifier: NCT01243073     History of Changes
Other Study ID Numbers: CP14B015
Study First Received: November 11, 2010
Last Updated: March 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Geron Corporation:
imetelstat
imetelstat sodium
GRN163L
telomerase inhibitor
telomerase
essential thrombocytosis
essential thrombocythemia
ET
polycythemia vera
PV

Additional relevant MeSH terms:
Polycythemia
Polycythemia Vera
Thrombocythemia, Essential
Thrombocytosis
Hematologic Diseases
Myeloproliferative Disorders
Bone Marrow Diseases
Blood Coagulation Disorders
Blood Platelet Disorders
Hemorrhagic Disorders

ClinicalTrials.gov processed this record on August 21, 2014