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

Sponsor

Geron Corporation (Industry)

Overall Status

Completed

CT.gov ID

NCT01243073

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

1.7

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Essential Thrombocythemia Polycythemia Vera	Drug: Imetelstat	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (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

Study Start Date :

Dec 1, 2010

Actual Primary Completion Date :

Oct 1, 2013

Actual Study Completion Date :

Apr 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: imetelstat Induction dosing of 9.4 mg/kg weekly, followed by intermittent maintenance dosing.	Drug: Imetelstat

Arm

Intervention/Treatment

Experimental: imetelstat

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

Drug: Imetelstat

Outcome Measures

Primary Outcome Measures

Hematologic Response [From time of first dose (cycle 1 day 1) through end of study (12 mos after last participant is dosed)]
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 [From time of first dose (cycle 1 day 1) through end of study (12 mos after last paricipant is dosed)]
The safety and tolerability of imtelstat will be assessed by the incidence, nature, relatedness and severity of adverse events, laboratory abnormalities and vital signs.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010
2	MDACC - Orlando	Orlando	Florida	United States	32806
3	University of Chicago	Chicago	Illinois	United States	60637
4	Johns Hopkins University - Bunting Blaustein Cancer Research Building	Baltimore	Maryland	United States	21205
5	Saint Francis Hospital	Greenville	South Carolina	United States	29601
6	MD Anderson Cancer Center	Houston	Texas	United States	77030
7	University Hospital of Essen - West German Cancer Center	Essen		Germany
8	Medizinische Klinik II, Abt. Hämatologie und Onkologie - Johann Wolfgang Goethe Universität	Frankfurt		Germany	D-60590
9	SLK-Kliniken GmbH	Heilbronn		Germany
10	Hematology Oncology Center - Ludwig-Maximilians, University Munich Medical School	Munich		Germany	80331
11	University Hospital Regensburg - Uniklinik Regensburg	Regensburg		Germany
12	INSELSPITAL, University Hospital Bern	Bern		Switzerland	CH - 3010