Essential thrombocythemia MedDRA version: 16.0 Level: PT Classification code 10015493 Term: Essential thrombocythaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Geron Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Willing and able to sign an informed consent. -Male or female, aged 18 years or older. -Patients with ET requiring cytoreduction who have failed or are intolerant to at least one prior therapy, or who refuse standard therapy. -Confirmed diagnosis of ET by WHO criteria. -ECOG performance status 0–2. -Laboratory criteria (within 14 days of first study drug administration) in compliance with protocol limits. -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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: -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 antiarrhythmic 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. -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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To obtain a preliminary estimate of efficacy of imetelstat, as measured by best hematologic response, in patients with ET who have failed or are intolerant to at least one prior therapy, or who have refused standard therapy.;Secondary Objective: The secondary objectives of this study are as follows: •To characterize the safety and tolerability of imetelstat in patients with ET; •To determine the durability of hematologic response; •To evaluate molecular response in patients with JAK2 V617F and/or MPL W515 mutations within 2 years of therapy; • To evaluate BM histologic response within the first 2 years of imetelstat therapy; • To evaluate clinicohematologic response within the first year of imetelstat therapy using the modified European LeukemiaNet response criteria;Primary end point(s): Efficacy will be determined by best overall hematologic response rate (CR + partial response [PR]) beginning within the first year of imetelstat therapy maintained for at least 4 consecutive weeks, defined as follows: -CR: Platelet count = 400 x 103/µL in the absence of new thromboembolic events; -PR: = 600 x 103/µL OR a 50% reduction in platelet counts (but > 400 x 103/µL) in the absence of new thromboembolic events. ;Timepoint(s) of evaluation of this end point: - Hematologic response prior to every imetelstat dose and molecular response every 12 (± 4) weeks - Clinicohematologic response (including evaluation of splenomegaly) at screening and every 12 (± 4) weeks - A repeat BM biopsy and aspirate will be performed after completing Cycle 6 (6 months) of study treatment when the patient is in a hematologic CR, and at the end of 12 cycles (12 months) or 1 year to assess histologic response. For patients who continue to receive treatment beyond 1 year, BM biopsies should be obtained every 6 months as long as the patient is in a hematologic CR - Additional BM biopsies and aspirates will be performed every 12 (± 4) weeks (after completion of Cycles 3 [Week 12], 9 [Week | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Duration of hematologic response - Rate of molecular response (CR and PR) within 2 years of therapy in patients with a molecular mutation (JAK2 or MPL) at baseline - Rate of BM histologic response within 2 years of therapy - Rate of clinicohematologic response within the first year of therapy as defined by the modified European LeukemiaNet consensus criteria (Section 8.8.4.4 and Table 8), as measured by the investigator;Timepoint(s) of evaluation of this end point: - Hematologic response prior to every imetelstat dose and molecular response every 12 (± 4) weeks - Clinicohematologic response (including evaluation of splenomegaly) at screening and every 12 (± 4) weeks - A repeat BM biopsy and aspirate will be performed after completing Cycle 6 (6 months) of study treatment when the patient is in a hematologic CR, and at the end of 12 cycles (12 months) or 1 year to assess histologic response. For patients who continue to receive treatment beyond 1 year, BM biopsies should be obtained every 6 months as long as the patient is in a hematologic CR - Additional BM biopsies and aspirates will be performed every 12 (± 4) weeks (after completion of Cycles 3 [Week 12], 9 [Week 36], and 12 [Week 48]) in patients at select study centers | — |
Countries
Germany, Switzerland, United States
Outcome results
None listed