Open Label Study to Evaluate the Activity of Imetelstat in Patients With Essential Thrombocythemia or Polycythemia Vera

NCT01243073 | Completed Phase 2

• 1 other identifier: CP14B015
• Study Type: interventional
• Target: 20
• Locations: 3 countries
• Sites: 12

Brief Summary

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.

Conditions

Essential Thrombocythemia; Polycythemia Vera

Keywords

imetelstat; imetelstat sodium; GRN163L; telomerase inhibitor; telomerase; essential thrombocytosis; essential thrombocythemia; ET; polycythemia vera; PV

Outcome Measures

Primary Outcomes (1)

• Hematologic Response

  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.

  From time of first dose (cycle 1 day 1) through end of study (12 mos after last participant is dosed)

Secondary Outcomes (1)

• Safety and tolerability: Number of Patients with Hematological Toxicities, Non-Heme Grade 3 and 4 AEs, and Hemorrhagic Events

  From time of first dose (cycle 1 day 1) through end of study (12 mos after last paricipant is dosed)

Study Arms (1)

imetelstat

EXPERIMENTAL

Induction dosing of 9.4 mg/kg weekly, followed by intermittent maintenance dosing.

Drug: Imetelstat

Interventions

Imetelstat DRUG

imetelstat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Geron Corporation: lead

Study Sites (12)

City of Hope

Duarte, California, 91010, United States

Location

MDACC - Orlando

Orlando, Florida, 32806, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Johns Hopkins University - Bunting Blaustein Cancer Research Building

Baltimore, Maryland, 21205, United States

Location

Saint Francis Hospital

Greenville, South Carolina, 29601, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University Hospital of Essen - West German Cancer Center

Essen, Germany

Location

Medizinische Klinik II, Abt. Hämatologie und Onkologie - Johann Wolfgang Goethe Universität

Frankfurt, D-60590, Germany

Location

SLK-Kliniken GmbH

Heilbronn, Germany

Location

Hematology Oncology Center - Ludwig-Maximilians, University Munich Medical School

Munich, 80331, Germany

Location

University Hospital Regensburg - Uniklinik Regensburg

Regensburg, Germany

Location

INSELSPITAL, University Hospital Bern

Bern, CH - 3010, Switzerland

Location

Related Publications (2)

• Oppliger Leibundgut E, Haubitz M, Burington B, Ottmann OG, Spitzer G, Odenike O, McDevitt MA, Roth A, Snyder DS, Baerlocher GM. Dynamics of mutations in patients with essential thrombocythemia treated with imetelstat. Haematologica. 2021 Sep 1;106(9):2397-2404. doi: 10.3324/haematol.2020.252817.

  PMID: 32732354 DERIVED

• Baerlocher GM, Oppliger Leibundgut E, Ottmann OG, Spitzer G, Odenike O, McDevitt MA, Roth A, Daskalakis M, Burington B, Stuart M, Snyder DS. Telomerase Inhibitor Imetelstat in Patients with Essential Thrombocythemia. N Engl J Med. 2015 Sep 3;373(10):920-8. doi: 10.1056/NEJMoa1503479.

  PMID: 26332546 DERIVED

MeSH Terms

Conditions

Thrombocythemia, Essential; Polycythemia Vera

Interventions

imetelstat

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombocytosis; Blood Platelet Disorders; Myeloproliferative Disorders; Bone Marrow Diseases; Hemorrhagic Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2010
• First Posted: November 18, 2010
• Study Start: December 1, 2010
• Primary Completion: October 1, 2013
• Study Completion: April 1, 2015
• Last Updated: January 26, 2016

Record last verified: 2015-12

Locations

CH (1); US (6); DE (5)