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| ID | Type | Description | Link |
|---|---|---|---|
| 63935937MYF2001 | Other Identifier | Geron Corporation | |
| 2015-000946-41 | EudraCT Number |
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The purpose of this study is to evaluate the efficacy and safety of 2 dose regimens of imetelstat in participants with intermediate-2 or high-risk myelofibrosis (MF) whose disease is relapsed after or is refractory to Janus Kinase (JAK) inhibitor treatment. Key secondary endpoint includes overall survival.
This is a randomized (study medication assigned to participants by chance), multicenter (more than one hospital, medical school team or medical clinic work on a medical research study) study of 2 dosing regimens (treatment arms) of single-agent imetelstat in participants with intermediate-2 or high risk myelofibrosis (MF) whose disease is relapsed after or refractory to Janus Kinase (JAK) inhibitor treatment. The main study consists of 3 parts: Screening Phase (21 days before randomization); Treatment Phase (from randomization until study drug discontinuation); and Follow up Phase (until death, lost to follow-up, withdrawal of consent or study end, whichever occurs first). Participants received imetelstat 9.4 milligram (mg)/kilogram (kg) intravenously (IV) for every 3 weeks until disease progression, unacceptable toxicity, or study end OR imetelstat 4.7 mg/kg IV for every 3 weeks until disease progression, unacceptable toxicity, or study end. Initially, all participants were blinded to the treatment. After the first interim analysis, treatment for all participants was unblinded and participants assigned to the imetelstat 4.7 mg/kg arm could continue with their same imetelstat dose or have it increased to 9.4 mg/kg at the investigator's discretion. The percentage of spleen response and symptom response were evaluated as co-primary endpoints. Following completion of the primary analysis, participants benefiting from study treatment could continue to receive imetelstat in Extension phase for up to 2 years or until loss of benefit or unacceptable toxicity. Participants who had already stopped study treatment could enter the Extension phase to continue follow up for safety via serious adverse event collection and for survival status.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Imetelstat 4.7 mg/kg | Experimental |
| |
| Imetelstat 9.4 mg/kg | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Imetelstat 4.7 mg/kg | Drug | Participants received imetelstat 4.7 mg/kg of body weight as intravenous infusion on Day 1 of each 21-day cycle. Study drug was administered intravenously until disease progression, unacceptable toxicity, or study end. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Spleen Response | Spleen response rate is defined as the percentage of participants who achieved ≥ 35% reduction in spleen volume at Week 24 from baseline performed by the IRC using magnetic resonance imaging (MRI). | Week 24 |
| Percentage of Participants With Symptom Response | Symptom response rate is defined as percentage of participants who achieved ≥ 50% reduction in total symptom score (TSS) at Week 24 from baseline as measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF) version 2.0 diary. The MFSAF assessed following symptoms due to Myelofibrosis (MF): night sweats, itchiness, abdominal discomfort, pain under ribs on left side, feeling of fullness, bone or muscle pain and degree of inactivity. Each item is scored on a scale of 0 (absent) to 10 (worst imaginable) with higher scores indicating more severe symptoms and greater inactivity. The total score ranges from 0-70, where 0 indicates absent/as good as it can be and 70 indicates worst imaginable/as bad as it can be. | Week 24 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Overall Response as Per Modified 2013 International Working Group - Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) Criteria | Overall Response Rate: % of participants with complete remission (CR) or partial remission (PR) per modified IWG-MRT.CR: bone marrow: normocellular <5% blasts, ≤Grade 1 fibrosis; immature myeloid cells in peripheral blood (PB):<2%;hemoglobin (Hb):10 g/dL-upper limit of normal (ULN); neutrophils:1*10^9/L-ULN; platelets: 100*10^9/L-ULN; spleen:not palpable and ≤350ml volume; extramedullary hematopoiesis (EMH): no non-hepato-splenic EMH; symptoms: >70% improvement in symptom score per modified MFSAF v2.0 TSS. PR: bone marrow: normocellular: <5% blasts ≤ Grade 1 fibrosis or not meeting bone marrow remission criteria; Immature myeloid cells in PB: <2%; Hb: 8.5 -<10 g/dL-ULN or 10 g/dL-ULN; neutrophils: 1*10^9/L-ULN; platelets: 50 -<100*10^9/L-ULN; spleen: ≥35% splenic volumetric reduction by MRI or not palpable; EMH: no non-hepato-splenic EMH;symptoms: >50% improvement in symptom score per modified MFSAF v2.0 TSS. All response categories, benefit must last >12 weeks to qualify as response. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Study Clinical Team | Geron Corporation | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Birmingham | Alabama | United States | ||||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34138638 | Derived | Mascarenhas J, Komrokji RS, Palandri F, Martino B, Niederwieser D, Reiter A, Scott BL, Baer MR, Hoffman R, Odenike O, Vannucchi AM, Bussolari J, Zhu E, Rose E, Sherman L, Dougherty S, Sun L, Huang F, Wan Y, Feller FM, Rizo A, Kiladjian JJ. Randomized, Single-Blind, Multicenter Phase II Study of Two Doses of Imetelstat in Relapsed or Refractory Myelofibrosis. J Clin Oncol. 2021 Sep 10;39(26):2881-2892. doi: 10.1200/JCO.20.02864. Epub 2021 Jun 17. |
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A total of 107 participants with Intermediate-2 or High-Risk Myelofibrosis (MF) Relapsed/Refractory to Janus Kinase (JAK) Inhibitor were randomly assigned to 1 of 2 treatment arms into 1:1 ratio to imetelstat 4.7 or imetelstat 9.4 mg/kg of body weight. Eligible participants were stratified based on a) spleen size ≥ 15 cm below the left costal margin by palpation (yes vs. no) and b) platelet count at study entry (platelets ≥75 x 10^9/L [Per Liter] and <150 x 10^9L vs. ≥150 x 10^9L).
Participants were enrolled at 55 investigative sites in Belgium, Canada, France, Germany, Israel, Italy, Korea, Spain, Taiwan, United Kingdom, and the United States from August 28, 2015, to 25 October 2016. Data analyses include all data through the data cut-off date February 07, 2020.
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| ID | Title | Description |
|---|---|---|
| FG000 | Imetelstat 4.7 mg/kg | Participants received imetelstat 4.7 mg/kg of body weight as intravenous infusion on Day 1 of each 21-day cycle until disease progression, unacceptable toxicity, or study end. After the first interim analysis, treatment for all participants was unblinded and participants assigned to the imetelstat 4.7 mg/kg arm could continue with their same imetelstat dose or have it increased to 9.4 mg/kg at the investigator's discretion. After the end of main study, participants who were receiving benefit from study treatment opted to continue to receive imetelstat during the Extension Phase until there is loss of benefit or unacceptable toxicity. (Maximum duration on study was approximately 2.3 years and Maximum duration on extension phase was approximately 1.8 years). |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 28, 2019 | Mar 26, 2021 |
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Initially single-blind; treatments unmasked after 1st Interim Analysis and continued as open-label treatment.
| Imetelstat 9.4 mg/kg | Drug | Participants received imetelstat 9.4 mg/kg of body weight as intravenous infusion on Day 1 of each 21-day cycle until disease progression, unacceptable toxicity, or study end. |
|
| Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years) |
| Percentage of Participants With Clinical Improvement (CI) Per Modified 2013 IWG-MRT Criteria | CI per the modified 2013 IWG-MRT criteria defined as the achievement of anemia, spleen or symptoms response without progressive disease or increase in severity of anemia, thrombocytopenia, or neutropenia (Increase in severity of anemia constitutes the occurrence of new transfusion dependency or a ≥ 2.0 g/dL decrease in hemoglobin level from pretreatment baseline that lasts for at least 12 weeks. Increase in severity of thrombocytopenia or neutropenia is defined as a 2-grade decline, from pretreatment baseline, in platelet count or ANC, according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. In addition, assignment to CI requires a minimum platelet count of ≥ 25,000*10^9/L and ANC of ≥ 0.5*10^9/L.) For all response categories, benefit must last for >12 weeks to qualify as a response. | Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years) |
| Percentage of Participants With Clinical Response Per Modified 2013 IWG-MRT | Clinical response rate (CRR) was defined as percentage of participants who achieved CR, PR, or CI per modified 2013 IWG-MRT criteria. CR: bone marrow: normocellular <5% blasts, ≤Grade 1 fibrosis; immature myeloid cells in PB: <2%; Hb: 10 g/dL-ULN; neutrophils: 1*10^9/L-ULN; platelets: 100*10^9/L-ULN; spleen: not palpable and ≤350ml volume; EMH: no non-hepato-splenic EMH; symptoms: >70% improvement in symptom score per modified MFSAF v2.0 TSS. PR: bone marrow: normocellular: <5% blasts ≤ Grade 1 fibrosis or not meeting bone marrow remission criteria; Immature myeloid cells in PB: <2%; Hb: 8.5 -<10 g/dL-ULN or 10 g/dL-ULN; neutrophils: 1*10^9/L-ULN; platelets: 50 -<100*10^9/L-ULN; spleen: ≥35% splenic volumetric reduction by MRI or not palpable; EMH: no non-hepato-splenic EMH; symptoms: >50% improvement in symptom score per modified MFSAF v2.0 TSS. CI: achievement of anemia, spleen or symptoms response without PD or increase in severity of anemia, thrombocytopenia, or neutropenia. | Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years) |
| Percentage of Participants With Spleen Response Per Modified 2013 IWG-MRT Criteria | Spleen response per modified 2013 IWG-MRT criteria. Spleen response: a baseline splenomegaly that is palpable at 5-10 cm, below the left costal margin (LCM), becomes not palpable or a baseline splenomegaly that is palpable at >10 cm, below the LCM, decreases by ≥50%; A spleen response requires confirmation by MRI showing >35% spleen volume reduction (SVR). For response categories, benefit must last for >12 weeks to qualify as a response. Participants who achieved CI per modified IWG-MRT criteria considered as response with clinical improvement. Participants who met criteria for spleen response but had worsening cytopenias (and therefore did not meet criteria for clinical improvement) were considered to have a response without clinical improvement. The clinical improvement in IWG-MRT is defined as the achievement of anemia, spleen or symptoms response without progressive disease or increase in severity of anemia, thrombocytopenia, or neutropenia. | Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years) |
| Percentage of Participants With Symptoms Response Per Modified 2013 IWG-MRT Criteria | Symptoms response per modified 2013 IWG-MRT criteria. Symptoms Response: a ≥50% reduction in the modified MFSAF v2.0 TSS. For response category, benefit must last for >12 weeks to qualify as a response. Participants who achieved CI per modified IWG-MRT criteria considered as response with clinical improvement. Participants who met criteria for symptom response but had worsening cytopenias (and therefore did not meet criteria for clinical improvement) were considered to have a response without clinical improvement. The clinical improvement in IWG-MRT is defined as the achievement of anemia, spleen or symptoms response without progressive disease or increase in severity of anemia, thrombocytopenia, or neutropenia. | Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years) |
| Percentage of Participants With Anemia Response Per Modified 2013 IWG-MRT Criteria | Anemia response per modified 2013 IWG-MRT criteria. Anemia response is defined as participants with baseline Hb <10 g/dL but not meeting strict criteria for transfusion dependency: a ≥ 2 g/dL increase in Hb; Transfusion dependent participants at baseline: becoming transfusion independent. Transfusion independence is defined as absence of any pRBC transfusions for at least 12 "rolling" weeks. For response categories, benefit must last for >12 weeks to qualify as a response. Participants who achieved CI per modified IWG-MRT criteria considered as response with clinical improvement. Participants who met criteria for anemia response but had worsening cytopenias (and therefore did not meet criteria for clinical improvement) were considered to have a response without clinical improvement. The clinical improvement in IWG-MRT is defined as the achievement of anemia, spleen or symptoms response without progressive disease or increase in severity of anemia, thrombocytopenia, or neutropenia. | Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years) |
| Duration of Response (PR/CI/RWCI) as Per IWG-MRT Criteria | Duration of response (PR/CI/RWCI) is the duration from the date of initial documentation of a response to date of first documented evidence of PD or death, whichever occurs first. PR: BM: normocellular: <5% blasts ≤Grade 1 fibrosis/not meeting BM remission criteria; IMC in PB: <2%; Hb: 8.5 -<10 g/dL-ULN or 10 g/dL- ULN; neutrophils: 1*10^9/L-ULN; platelets: 50 -<100*10^9/L-ULN; spleen: ≥35% splenic volumetric reduction by MRI/not palpable; EMH: no non-hepato-splenic EMH; symptoms: >50% improvement in symptom score. CI: achievement of anemia, spleen or symptoms response without PD or increase in severity of anemia, thrombocytopenia, neutropenia. RWCI: Participants who met criteria for response but had worsening cytopenias. PD: Splenomegaly requires MRI showing ≥25% increase in spleen volume. | From date of initial documentation of a response to the date of first documented evidence of PD or death, whichever occurs first (approximately up to 2.3 years) |
| Overall Survival | Overall Survival is measured from the date of Cycle 1, Day 1 to the date of the participants death. If the participant's was alive or the vital status was unknown, OS was censored at the date that the participant is last known to be alive. | Day 1 of Cycle 1 (each cycle was of 21 days), up to the date of the participant's death (approximately up to 4.1 years) |
| Percentage of Participants With Clinically Meaningful Improvement in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-30 (QLQ-C30): Global Health Status | EORTC QLQ-C30 is a questionnaire to assess quality of life of cancer patients. The EORTC QLQ-C30 included 30 items resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) which are based on 4-point scale (1= Not at all to 4= Very much); and 1 global health status scale based on 7-point scale (1= Very poor to 7= Excellent). All scales and items are averaged, transformed to 0-100 scale; higher score=better level of functioning. Clinically meaningful improvement defined as change greater than half of the standard deviation at baseline in QLQ-C30 Global Health Status. | Up to end of the treatment (approximately up to 2.3 years) |
| EuroQol 5 Dimension 5 Level (EQ-5D-5L): Utility Score and Visual Analog Scale (VAS) | EQ-5D-5L is a standardized health-related quality of life questionnaire developed by EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal. EQ-5D-5L consists of two components: a health state profile and VAS. EQ-5D health state profile comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. The 5D-5L systems are converted into a single index utility score between 0 to 1, where higher score indicates a better health state. EQ-5D-5L- VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. | At the end of treatment, up to approximately 2.3 years |
| Percentage of Participants With Clinically Meaningful Improvement in Brief Pain Inventory (BPI) | The BPI rates the intensity of pain on 4 items (right now, worst, least, and average), and the interference in 7 areas (general activity, mood, walking ability, normal work, relations, sleep, enjoyment of life). Minimum value = 0; maximum value = 10. Higher scores indicate greater symptom severity/worse outcomes. Clinically meaningful improvement in BPI defined as change greater than half of the standard deviation at baseline. | Up to end of treatment (approximately up to 2.3 years) |
| Patient's Global Impression of Change (PGIC) | The PGIC was used to capture the participant's perspective of improvement or decline in MF symptoms over time. The PGIC had a 7-point response scale ranging from 1 to 7 where, (1=very much improved, 2= somewhat improved, 3= a little improved, 4=no change, 5= a little worse, 6= somewhat worse, 7=very much worse). | At the end of treatment, up to approximately 2.3 years |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | An AE is any untoward medical occurrence in a participant or clinical investigation participants administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. TEAEs were AEs with onset during or after the first dose of study drug, and within 30 days following the last dose of study drug. | Up to end of extension phase (approximately up to 4.2 years) |
| Maximum Observed Plasma Concentration (Cmax) of Imetelstat | 0 (before start of infusion), 1, 2, 3-5, 6-10, 12-16 and 18-24 hours post dose on Day 1 of Cycle 1 (each cycle was of 21 days) |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Imetelstat | 0 (before start of infusion), 1, 2, 3-5, 6-10, 12-16 and 18-24 hours post dose on Day 1 of Cycle 1 (each cycle was of 21 days) |
| Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC 0-24) of Imetelstat | 0 (before start of infusion), 1, 2, 3-5, 6-10, 12-16 and 18-24 hours post dose on Day 1 of Cycle 1 (each cycle was of 21 days) |
| Area Under the Plasma Concentration-Time Profile From Time Zero to Infinity (AUC0-inf) of Imetelstat | 0 (before start of infusion), 1, 2, 3-5, 6-10, 12-16 and 18-24 hours post dose on Day 1 of Cycle 1 (each cycle was of 21 days) |
| Elimination Half-Life (t1/2) of Imetelstat | Elimination half-life (t 1/2) is associated with the terminal slope (lambda [z]) of the semi logarithmic drug concentration-time curve, calculated as 0.693/lambda(z). | 0 (before start of infusion), 1, 2, 3-5, 6-10, 12-16 and 18-24 hours post dose on Day 1 of Cycle 1 (each cycle was of 21 days) |
| Total Systemic Clearance (CL) of Imetelstat | 0 (before start of infusion), 1, 2, 3-5, 6-10, 12-16 and 18-24 hours post dose on Day 1 of Cycle 1 (each cycle was of 21 days) |
| Volume of Distribution (Vd) of Imetelstat | 0 (before start of infusion), 1, 2, 3-5, 6-10, 12-16 and 18-24 hours post dose on Day 1 of Cycle 1 (each cycle was of 21 days) |
| Duarte |
| California |
| United States |
| La Jolla | California | United States |
| Los Angeles | California | United States |
| Stanford | California | United States |
| Washington D.C. | District of Columbia | United States |
| Tampa | Florida | United States |
| West Palm Beach | Florida | United States |
| Chicago | Illinois | United States |
| Louisville | Kentucky | United States |
| Baltimore | Maryland | United States |
| Ann Arbor | Michigan | United States |
| Rochester | Minnesota | United States |
| St Louis | Missouri | United States |
| Buffalo | New York | United States |
| Lake Success | New York | United States |
| New York | New York | United States |
| The Bronx | New York | United States |
| Charlotte | North Carolina | United States |
| Durham | North Carolina | United States |
| Winston-Salem | North Carolina | United States |
| Cincinnati | Ohio | United States |
| Philadelphia | Pennsylvania | United States |
| Greenville | South Carolina | United States |
| Watertown | South Dakota | United States |
| Nashville | Tennessee | United States |
| Dallas | Texas | United States |
| Seattle | Washington | United States |
| Milwaukee | Wisconsin | United States |
| Antwerp | Belgium |
| Bruges | Belgium |
| Brussels | Belgium |
| Leuven | Belgium |
| Edmonton | Alberta | Canada |
| Winnipeg | Manitoba | Canada |
| Montreal | Quebec | Canada |
| Angers | France |
| Lille | France |
| Marseille | France |
| Paris | France |
| Pierre-Bénite | France |
| Toulouse | France |
| Aachen | Germany |
| Cologne | Germany |
| Dresden | Germany |
| Düsseldorf | Germany |
| Frankfurt | Germany |
| Hamburg | Germany |
| Heidelberg | Germany |
| Leipzig | Germany |
| Mannheim | Germany |
| Rostock | Germany |
| Haifa | Israel |
| Jerusalem | Israel |
| Kfar Saba | Israel |
| Nahariya | Israel |
| Ramat Gan | Israel |
| Tel Aviv | Israel |
| Bergamo | Italy |
| Bologna | Italy |
| Seoul | South Korea |
| Barcelona | Spain |
| Las Palmas de Gran Canaria | Spain |
| Madrid | Spain |
| Salamanca | Spain |
| Valencia | Spain |
| Chiayi City | Taiwan |
| Taipei | Taiwan |
| Birmingham | United Kingdom |
| Glasgow | United Kingdom |
| London | United Kingdom |
| Oxford | United Kingdom |
| FG001 | Imetelstat 9.4 mg/kg | Participants received imetelstat 9.4 mg/kg of body weight as intravenous infusion on Day 1 of each 21-day cycle until disease progression, unacceptable toxicity, or study end. After the end of the main study, participants who were receiving benefit from study treatment opted to continue to receive imetelstat during the Extension Phase until there is loss of benefit or unacceptable toxicity. (Maximum duration on study was approximately 2.3 years and Maximum duration on extension phase was approximately 1.8 years). |
| Treated |
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| COMPLETED | Disposition data is reported until the end of study. |
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| NOT COMPLETED |
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Intent-to-Treat (ITT) analysis set included all participants randomized into the study and classified according to their assigned treatment group.
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| ID | Title | Description |
|---|---|---|
| BG000 | Imetelstat 4.7 mg/kg | Participants received imetelstat 4.7 mg/kg of body weight as intravenous infusion on Day 1 of each 21-day cycle until disease progression, unacceptable toxicity, or study end. After the first interim analysis, treatment for all participants was unblinded and participants assigned to the imetelstat 4.7 mg/kg arm could continue with their same imetelstat dose or have it increased to 9.4 mg/kg at the investigator's discretion. After the end of main study, participants who were receiving benefit from study treatment opted to continue to receive imetelstat during the Extension Phase until there is loss of benefit or unacceptable toxicity. (Maximum duration on study was approximately 2.3 years and Maximum duration on extension phase was approximately 1.8 years). |
| BG001 | Imetelstat 9.4 mg/kg | Participants received imetelstat 9.4 mg/kg of body weight as intravenous infusion on Day 1 of each 21-day cycle until disease progression, unacceptable toxicity, or study end. After the end of the main study, participants who were receiving benefit from study treatment opted to continue to receive imetelstat during the Extension Phase until there is loss of benefit or unacceptable toxicity. (Maximum duration on study was approximately 2.3 years and Maximum duration on extension phase was approximately 1.8 years). |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Region | Count of Participants | Participants |
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| Spleen Size by Palpation | Number analyzed signifies the number of participants with data available for spleen size palpitation. | Mean | Standard Deviation | centimeter (cm) |
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| Platelet Count | Count of Participants | Participants |
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| Eastern Cooperative Oncology Group (ECOG) Score | ECOG Performance Score has 5 grades.0= Fully active, able to carry on all predisease performance without restriction;1= Restricted in physically strenuous activity but ambulatory and able to carry out work on a light or sedentary nature, eg, light housework, office work;2= Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours;3= Capable of only limited self-care; confined to bed or chair more than 50% of waking hours;4= Completely disabled. Cannot carry on any self-care.Totally confined to bed or chair;5= Dead. | Count of Participants | Participants |
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| Time from Last JAKi Treatment | Median | Full Range | months |
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| Duration of Prior JAKi Treatment | Median | Full Range | months |
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| Dynamic International Prognostic Scoring System (DIPSS) | DIPSS stratifies primary myelofibrosis (PMF) into four risk categories (low, intermediate 1, intermediate 2, and high risk), based on 5 clinical factors; Age>65, Hemoglobin <10gm/dL, Leukocytes >10 (9)/L, circulating blasts ≥1%, and constitutional symptoms. | Count of Participants | Participants |
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| Type of Myelofibrosis (MF) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
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| Primary | Percentage of Participants With Spleen Response | Spleen response rate is defined as the percentage of participants who achieved ≥ 35% reduction in spleen volume at Week 24 from baseline performed by the IRC using magnetic resonance imaging (MRI). | Treated analysis set included all participants who received at least 1 dose of study drug. | Posted | Number | 95% Confidence Interval | percentage of participants | Week 24 |
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| Primary | Percentage of Participants With Symptom Response | Symptom response rate is defined as percentage of participants who achieved ≥ 50% reduction in total symptom score (TSS) at Week 24 from baseline as measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF) version 2.0 diary. The MFSAF assessed following symptoms due to Myelofibrosis (MF): night sweats, itchiness, abdominal discomfort, pain under ribs on left side, feeling of fullness, bone or muscle pain and degree of inactivity. Each item is scored on a scale of 0 (absent) to 10 (worst imaginable) with higher scores indicating more severe symptoms and greater inactivity. The total score ranges from 0-70, where 0 indicates absent/as good as it can be and 70 indicates worst imaginable/as bad as it can be. | Treated analysis set included all participants who received at least 1 dose of study drug. | Posted | Number | 95% Confidence Interval | percentage of participants | Week 24 |
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| Secondary | Percentage of Participants With Overall Response as Per Modified 2013 International Working Group - Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) Criteria | Overall Response Rate: % of participants with complete remission (CR) or partial remission (PR) per modified IWG-MRT.CR: bone marrow: normocellular <5% blasts, ≤Grade 1 fibrosis; immature myeloid cells in peripheral blood (PB):<2%;hemoglobin (Hb):10 g/dL-upper limit of normal (ULN); neutrophils:1*10^9/L-ULN; platelets: 100*10^9/L-ULN; spleen:not palpable and ≤350ml volume; extramedullary hematopoiesis (EMH): no non-hepato-splenic EMH; symptoms: >70% improvement in symptom score per modified MFSAF v2.0 TSS. PR: bone marrow: normocellular: <5% blasts ≤ Grade 1 fibrosis or not meeting bone marrow remission criteria; Immature myeloid cells in PB: <2%; Hb: 8.5 -<10 g/dL-ULN or 10 g/dL-ULN; neutrophils: 1*10^9/L-ULN; platelets: 50 -<100*10^9/L-ULN; spleen: ≥35% splenic volumetric reduction by MRI or not palpable; EMH: no non-hepato-splenic EMH;symptoms: >50% improvement in symptom score per modified MFSAF v2.0 TSS. All response categories, benefit must last >12 weeks to qualify as response. | Treated analysis set included all participants who received at least 1 dose of study drug. | Posted | Number | 95% Confidence Interval | percentage of participants | Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years) |
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| Secondary | Percentage of Participants With Clinical Improvement (CI) Per Modified 2013 IWG-MRT Criteria | CI per the modified 2013 IWG-MRT criteria defined as the achievement of anemia, spleen or symptoms response without progressive disease or increase in severity of anemia, thrombocytopenia, or neutropenia (Increase in severity of anemia constitutes the occurrence of new transfusion dependency or a ≥ 2.0 g/dL decrease in hemoglobin level from pretreatment baseline that lasts for at least 12 weeks. Increase in severity of thrombocytopenia or neutropenia is defined as a 2-grade decline, from pretreatment baseline, in platelet count or ANC, according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. In addition, assignment to CI requires a minimum platelet count of ≥ 25,000*10^9/L and ANC of ≥ 0.5*10^9/L.) For all response categories, benefit must last for >12 weeks to qualify as a response. | Treated analysis set included all participants who received at least 1 dose of study drug. | Posted | Number | percentage of participants | Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years) |
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| Secondary | Percentage of Participants With Clinical Response Per Modified 2013 IWG-MRT | Clinical response rate (CRR) was defined as percentage of participants who achieved CR, PR, or CI per modified 2013 IWG-MRT criteria. CR: bone marrow: normocellular <5% blasts, ≤Grade 1 fibrosis; immature myeloid cells in PB: <2%; Hb: 10 g/dL-ULN; neutrophils: 1*10^9/L-ULN; platelets: 100*10^9/L-ULN; spleen: not palpable and ≤350ml volume; EMH: no non-hepato-splenic EMH; symptoms: >70% improvement in symptom score per modified MFSAF v2.0 TSS. PR: bone marrow: normocellular: <5% blasts ≤ Grade 1 fibrosis or not meeting bone marrow remission criteria; Immature myeloid cells in PB: <2%; Hb: 8.5 -<10 g/dL-ULN or 10 g/dL-ULN; neutrophils: 1*10^9/L-ULN; platelets: 50 -<100*10^9/L-ULN; spleen: ≥35% splenic volumetric reduction by MRI or not palpable; EMH: no non-hepato-splenic EMH; symptoms: >50% improvement in symptom score per modified MFSAF v2.0 TSS. CI: achievement of anemia, spleen or symptoms response without PD or increase in severity of anemia, thrombocytopenia, or neutropenia. | Treated analysis set included all participants who received at least 1 dose of study drug. | Posted | Number | 95% Confidence Interval | percentage of participants | Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years) |
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| Secondary | Percentage of Participants With Spleen Response Per Modified 2013 IWG-MRT Criteria | Spleen response per modified 2013 IWG-MRT criteria. Spleen response: a baseline splenomegaly that is palpable at 5-10 cm, below the left costal margin (LCM), becomes not palpable or a baseline splenomegaly that is palpable at >10 cm, below the LCM, decreases by ≥50%; A spleen response requires confirmation by MRI showing >35% spleen volume reduction (SVR). For response categories, benefit must last for >12 weeks to qualify as a response. Participants who achieved CI per modified IWG-MRT criteria considered as response with clinical improvement. Participants who met criteria for spleen response but had worsening cytopenias (and therefore did not meet criteria for clinical improvement) were considered to have a response without clinical improvement. The clinical improvement in IWG-MRT is defined as the achievement of anemia, spleen or symptoms response without progressive disease or increase in severity of anemia, thrombocytopenia, or neutropenia. | Treated analysis set included all participants who received at least 1 dose of study drug. All treated participants were evaluated for each response. | Posted | Number | percentage of participants | Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years) |
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| Secondary | Percentage of Participants With Symptoms Response Per Modified 2013 IWG-MRT Criteria | Symptoms response per modified 2013 IWG-MRT criteria. Symptoms Response: a ≥50% reduction in the modified MFSAF v2.0 TSS. For response category, benefit must last for >12 weeks to qualify as a response. Participants who achieved CI per modified IWG-MRT criteria considered as response with clinical improvement. Participants who met criteria for symptom response but had worsening cytopenias (and therefore did not meet criteria for clinical improvement) were considered to have a response without clinical improvement. The clinical improvement in IWG-MRT is defined as the achievement of anemia, spleen or symptoms response without progressive disease or increase in severity of anemia, thrombocytopenia, or neutropenia. | Treated analysis set included all participants who received at least 1 dose of study drug. All treated participants were evaluated for each response. | Posted | Number | percentage of participants | Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years) |
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| Secondary | Percentage of Participants With Anemia Response Per Modified 2013 IWG-MRT Criteria | Anemia response per modified 2013 IWG-MRT criteria. Anemia response is defined as participants with baseline Hb <10 g/dL but not meeting strict criteria for transfusion dependency: a ≥ 2 g/dL increase in Hb; Transfusion dependent participants at baseline: becoming transfusion independent. Transfusion independence is defined as absence of any pRBC transfusions for at least 12 "rolling" weeks. For response categories, benefit must last for >12 weeks to qualify as a response. Participants who achieved CI per modified IWG-MRT criteria considered as response with clinical improvement. Participants who met criteria for anemia response but had worsening cytopenias (and therefore did not meet criteria for clinical improvement) were considered to have a response without clinical improvement. The clinical improvement in IWG-MRT is defined as the achievement of anemia, spleen or symptoms response without progressive disease or increase in severity of anemia, thrombocytopenia, or neutropenia. | Treated analysis set included all participants who received at least 1 dose of study drug. All treated participants were evaluated for each response. | Posted | Number | percentage of participants | Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years) |
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| Secondary | Duration of Response (PR/CI/RWCI) as Per IWG-MRT Criteria | Duration of response (PR/CI/RWCI) is the duration from the date of initial documentation of a response to date of first documented evidence of PD or death, whichever occurs first. PR: BM: normocellular: <5% blasts ≤Grade 1 fibrosis/not meeting BM remission criteria; IMC in PB: <2%; Hb: 8.5 -<10 g/dL-ULN or 10 g/dL- ULN; neutrophils: 1*10^9/L-ULN; platelets: 50 -<100*10^9/L-ULN; spleen: ≥35% splenic volumetric reduction by MRI/not palpable; EMH: no non-hepato-splenic EMH; symptoms: >50% improvement in symptom score. CI: achievement of anemia, spleen or symptoms response without PD or increase in severity of anemia, thrombocytopenia, neutropenia. RWCI: Participants who met criteria for response but had worsening cytopenias. PD: Splenomegaly requires MRI showing ≥25% increase in spleen volume. | Treated analysis set included all participants who received at least 1 dose of study drug. Here, "overall number of participants analyzed" signifies participants who were responders (PR/CI/RWCI) at any time. | Posted | Median | 95% Confidence Interval | weeks | From date of initial documentation of a response to the date of first documented evidence of PD or death, whichever occurs first (approximately up to 2.3 years) |
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| Secondary | Overall Survival | Overall Survival is measured from the date of Cycle 1, Day 1 to the date of the participants death. If the participant's was alive or the vital status was unknown, OS was censored at the date that the participant is last known to be alive. | Treated analysis set included all participants who received at least 1 dose of study drug. | Posted | Median | 95% Confidence Interval | months | Day 1 of Cycle 1 (each cycle was of 21 days), up to the date of the participant's death (approximately up to 4.1 years) |
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| Secondary | Percentage of Participants With Clinically Meaningful Improvement in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-30 (QLQ-C30): Global Health Status | EORTC QLQ-C30 is a questionnaire to assess quality of life of cancer patients. The EORTC QLQ-C30 included 30 items resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) which are based on 4-point scale (1= Not at all to 4= Very much); and 1 global health status scale based on 7-point scale (1= Very poor to 7= Excellent). All scales and items are averaged, transformed to 0-100 scale; higher score=better level of functioning. Clinically meaningful improvement defined as change greater than half of the standard deviation at baseline in QLQ-C30 Global Health Status. | Treated analysis set included all participants who received at least 1 dose of study drug. Here, "overall number of participants analyzed" signifies the number of participants who had data at both baseline and end of treatment. | Posted | Number | percentage of participants | Up to end of the treatment (approximately up to 2.3 years) |
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| Secondary | EuroQol 5 Dimension 5 Level (EQ-5D-5L): Utility Score and Visual Analog Scale (VAS) | EQ-5D-5L is a standardized health-related quality of life questionnaire developed by EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal. EQ-5D-5L consists of two components: a health state profile and VAS. EQ-5D health state profile comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. The 5D-5L systems are converted into a single index utility score between 0 to 1, where higher score indicates a better health state. EQ-5D-5L- VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. | Treated analysis set included all participants who received at least 1 dose of study drug. Here "N"= participants who had data at both baseline and end of treatment. | Posted | Mean | Standard Deviation | score on a scale | At the end of treatment, up to approximately 2.3 years |
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| Secondary | Percentage of Participants With Clinically Meaningful Improvement in Brief Pain Inventory (BPI) | The BPI rates the intensity of pain on 4 items (right now, worst, least, and average), and the interference in 7 areas (general activity, mood, walking ability, normal work, relations, sleep, enjoyment of life). Minimum value = 0; maximum value = 10. Higher scores indicate greater symptom severity/worse outcomes. Clinically meaningful improvement in BPI defined as change greater than half of the standard deviation at baseline. | Treated analysis set included all participants who received at least 1 dose of study drug. Here, "overall number of participants analyzed" signifies participants who had data at both baseline and end of treatment and "Number analyzed" signifies the number of participants with data available for each specified category. | Posted | Number | percentage of participants | Up to end of treatment (approximately up to 2.3 years) |
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| Secondary | Patient's Global Impression of Change (PGIC) | The PGIC was used to capture the participant's perspective of improvement or decline in MF symptoms over time. The PGIC had a 7-point response scale ranging from 1 to 7 where, (1=very much improved, 2= somewhat improved, 3= a little improved, 4=no change, 5= a little worse, 6= somewhat worse, 7=very much worse). | Treated analysis set included all participants who received at least 1 dose of study drug. Here, "overall number of participants analyzed" signifies number of subjects who had data at both baseline and end of treatment. | Posted | Mean | Standard Deviation | score on a scale | At the end of treatment, up to approximately 2.3 years |
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| Secondary | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | An AE is any untoward medical occurrence in a participant or clinical investigation participants administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. TEAEs were AEs with onset during or after the first dose of study drug, and within 30 days following the last dose of study drug. | Safety analysis set included all participants who received at least 1 dose of study treatment. | Posted | Count of Participants | Participants | Up to end of extension phase (approximately up to 4.2 years) |
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| Secondary | Maximum Observed Plasma Concentration (Cmax) of Imetelstat | Pharmacokinetic (PK) subset included all participants who had serial PK sampling during cycle 1 treatment to determine the maximum plasma concentration of Imetelstat by noncompartmental PK analysis. | Posted | Mean | Standard Deviation | μg/mL | 0 (before start of infusion), 1, 2, 3-5, 6-10, 12-16 and 18-24 hours post dose on Day 1 of Cycle 1 (each cycle was of 21 days) |
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| Secondary | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Imetelstat | PK subset included all participants who had serial PK sampling during cycle 1 treatment to determine the time to reach maximum plasma concentration of imetelstat by noncompartmental PK analysis. | Posted | Median | Full Range | hr | 0 (before start of infusion), 1, 2, 3-5, 6-10, 12-16 and 18-24 hours post dose on Day 1 of Cycle 1 (each cycle was of 21 days) |
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| Secondary | Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC 0-24) of Imetelstat | PK subset included all participants who had serial PK sampling during cycle 1 treatment to determine the AUC 0-24 of Imetelstat by noncompartmental PK analysis. | Posted | Mean | Standard Deviation | μg*hr/mL | 0 (before start of infusion), 1, 2, 3-5, 6-10, 12-16 and 18-24 hours post dose on Day 1 of Cycle 1 (each cycle was of 21 days) |
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| Secondary | Area Under the Plasma Concentration-Time Profile From Time Zero to Infinity (AUC0-inf) of Imetelstat | PK subset included all participants who had serial PK sampling during cycle 1 treatment to determine AUC 0-inf of Imetelstat by noncompartmental PK analysis. | Posted | Mean | Standard Deviation | μg*h/mL | 0 (before start of infusion), 1, 2, 3-5, 6-10, 12-16 and 18-24 hours post dose on Day 1 of Cycle 1 (each cycle was of 21 days) |
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| Secondary | Elimination Half-Life (t1/2) of Imetelstat | Elimination half-life (t 1/2) is associated with the terminal slope (lambda [z]) of the semi logarithmic drug concentration-time curve, calculated as 0.693/lambda(z). | PK subset included all participants who had serial PK sampling during cycle 1 treatment to determine the t1/2 of Imetelstat by noncompartmental PK analysis. | Posted | Mean | Standard Deviation | hr | 0 (before start of infusion), 1, 2, 3-5, 6-10, 12-16 and 18-24 hours post dose on Day 1 of Cycle 1 (each cycle was of 21 days) |
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| Secondary | Total Systemic Clearance (CL) of Imetelstat | PK subset included all participants who had serial PK sampling during cycle 1 treatment to determine the CL of Imetelstat by noncompartmental PK analysis. | Posted | Mean | Standard Deviation | L/hr/kg | 0 (before start of infusion), 1, 2, 3-5, 6-10, 12-16 and 18-24 hours post dose on Day 1 of Cycle 1 (each cycle was of 21 days) |
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| Secondary | Volume of Distribution (Vd) of Imetelstat | PK population analysis set included all participants who received at least 1 dose of study drug and had at least 1 sample collected during treatment to determine the drug concentration. | Posted | Mean | Standard Deviation | L/kg | 0 (before start of infusion), 1, 2, 3-5, 6-10, 12-16 and 18-24 hours post dose on Day 1 of Cycle 1 (each cycle was of 21 days) |
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Up to end of extension phase (approximately up to 4.2 years)
Safety analysis set included all participants who received at least 1 dose of study treatment.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Imetelstat 4.7 mg/kg | Participants received imetelstat 4.7 mg/kg of body weight as intravenous infusion on Day 1 of each 21-day cycle until disease progression, unacceptable toxicity, or study end. After the first interim analysis, treatment for all participants was unblinded and participants assigned to the imetelstat 4.7 mg/kg arm could continue with their same imetelstat dose. After the end of main study, participants who were receiving benefit from study treatment opted to continue to receive imetelstat during the Extension Phase until there is loss of benefit or unacceptable toxicity. (Maximum duration on study was approximately 2.3 years and Maximum duration on extension phase was approximately 1.8 years). AEs for the 12 subjects whose dose was later escalated are included here for the period before dose escalation. | 34 | 48 | 24 | 48 | 47 | 48 |
| EG001 | Imetelstat 9.4 mg/kg | Participants received imetelstat 9.4 mg/kg of body weight as intravenous infusion on Day 1 of each 21-day cycle until disease progression, unacceptable toxicity, or study end. After the end of the main study, participants who were receiving benefit from study treatment opted to continue to receive imetelstat during the Extension Phase until there is loss of benefit or unacceptable toxicity. (Maximum duration on study was approximately 2.3 years and Maximum duration on extension phase was approximately 1.8 years). | 36 | 59 | 21 | 59 | 59 | 59 |
| EG002 | Imetelstat Dose Escalated From 4.7 mg/kg to 9.4 mg/kg | Participants initially treated with 4.7 mg/kg imetelstat in Imetelstat 4.7 mg/kg arm group were subsequently dose escalated to 9.4 mg/kg at the investigator's discretion. Dose escalation for these participants may occur at any cycle (each of 21-day cycle) of the treatment phase. After the end of main study, participants who were receiving benefit from study treatment opted to continue to receive imetelstat during the Extension Phase until there is loss of benefit or unacceptable toxicity. (Maximum duration on study was approximately 2.3 years and Maximum duration on extension phase was approximately 1.8 years). AEs reported in this column occurred after dose escalation. | 1 | 12 | 4 | 12 | 12 | 12 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Bone marrow failure | Blood and lymphatic system disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Haemolysis | Blood and lymphatic system disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Leukocytosis | Blood and lymphatic system disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Pancytopenia | Blood and lymphatic system disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Splenic artery thrombosis | Blood and lymphatic system disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Splenic infarction | Blood and lymphatic system disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Splenic vein thrombosis | Blood and lymphatic system disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Splenomegaly | Blood and lymphatic system disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Cardiac failure | Cardiac disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Cardiac failure congestive | Cardiac disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Cardiac tamponade | Cardiac disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Ascites | Gastrointestinal disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Melaena | Gastrointestinal disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Rectal haemorrhage | Gastrointestinal disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Chills | General disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Non-cardiac chest pain | General disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Hepatic failure | Hepatobiliary disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Hepatic function abnormal | Hepatobiliary disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Bacterial infection | Infections and infestations | MedDRA Version 21.1 | Systematic Assessment |
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| Bronchitis | Infections and infestations | MedDRA Version 21.1 | Systematic Assessment |
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| Cellulitis | Infections and infestations | MedDRA Version 21.1 | Systematic Assessment |
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| Escherichia bacteraemia | Infections and infestations | MedDRA Version 21.1 | Systematic Assessment |
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| Listeriosis | Infections and infestations | MedDRA Version 21.1 | Systematic Assessment |
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| Lung infection | Infections and infestations | MedDRA Version 21.1 | Systematic Assessment |
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| Ophthalmic herpes zoster | Infections and infestations | MedDRA Version 21.1 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA Version 21.1 | Systematic Assessment |
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| Pneumonia klebsiella | Infections and infestations | MedDRA Version 21.1 | Systematic Assessment |
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| Respiratory tract infection | Infections and infestations | MedDRA Version 21.1 | Systematic Assessment |
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| Sepsis | Infections and infestations | MedDRA Version 21.1 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA Version 21.1 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA Version 21.1 | Systematic Assessment |
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| Head injury | Injury, poisoning and procedural complications | MedDRA Version 21.1 | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA Version 21.1 | Systematic Assessment |
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| Failure to thrive | Metabolism and nutrition disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Fluid overload | Metabolism and nutrition disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Gout | Metabolism and nutrition disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Pulmonary congestion | Respiratory, thoracic and mediastinal disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Aneurysm ruptured | Vascular disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Haematoma | Vascular disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Haemorrhage | Vascular disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Rotator cuff syndrome | Musculoskeletal and connective tissue disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Myelofibrosis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 21.1 | Systematic Assessment |
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| Cerebral haemorrhage | Nervous system disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Encephalopathy | Nervous system disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Leukocytosis | Blood and lymphatic system disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Leukopenia | Blood and lymphatic system disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Splenomegaly | Blood and lymphatic system disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Palpitations | Cardiac disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Abdominal discomfort | Gastrointestinal disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Abdominal distension | Gastrointestinal disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Stomatitis | Gastrointestinal disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Toothache | Gastrointestinal disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Asthenia | General disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Chills | General disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Malaise | General disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Pain | General disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA Version 21.1 | Systematic Assessment |
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| Rhinovirus infection | Infections and infestations | MedDRA Version 21.1 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA Version 21.1 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA Version 21.1 | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA Version 21.1 | Systematic Assessment |
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| Blood alkaline phosphatase increased | Investigations | MedDRA Version 21.1 | Systematic Assessment |
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| Serum ferritin increased | Investigations | MedDRA Version 21.1 | Systematic Assessment |
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| Weight decreased | Investigations | MedDRA Version 21.1 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Gout | Metabolism and nutrition disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA Version 21.1 | Systematic Assessment |
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| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Pruritus generalised | Skin and subcutaneous tissue disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Coagulopathy | Blood and lymphatic system disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Aortic valve stenosis | Cardiac disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Deafness | Ear and labyrinth disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Hypothyroidism | Endocrine disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Photophobia | Eye disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Aphthous ulcer | Gastrointestinal disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Discomfort | General disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Inflammation | General disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Peripheral swelling | General disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA Version 21.1 | Systematic Assessment |
| |
| Periodontitis | Infections and infestations | MedDRA Version 21.1 | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA Version 21.1 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA Version 21.1 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA Version 21.1 | Systematic Assessment |
| |
| Chondropathy | Musculoskeletal and connective tissue disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Limb discomfort | Musculoskeletal and connective tissue disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Osteonecrosis of jaw | Musculoskeletal and connective tissue disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Rotator cuff syndrome | Musculoskeletal and connective tissue disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Amnesia | Nervous system disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Cognitive disorder | Nervous system disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Renal impairment | Renal and urinary disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Genital ulceration | Reproductive system and breast disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Pulmonary fibrosis | Respiratory, thoracic and mediastinal disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA Version 21.1 | Systematic Assessment |
| |
| Hot flush | Vascular disorders | MedDRA Version 21.1 | Systematic Assessment |
|
Consistent with Good Publication Practices and ICMJE guidelines, the sponsor shall have right to publish such primary (multicenter) data and information without approval from investigator. Investigator has right to publish study site-specific data after primary data published. If an investigator wishes to publish information from study, a copy of manuscript must be provided to sponsor for review at least 60 days before submission for publication or presentation.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Geron Corp. | 650-473-7700 | myf2001-info@geron.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 14, 2018 | Mar 26, 2021 | SAP_001.pdf |
| ID | Term |
|---|---|
| D055728 | Primary Myelofibrosis |
| D012008 | Recurrence |
| ID | Term |
|---|---|
| D009196 | Myeloproliferative Disorders |
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| C519562 | imetelstat |
Not provided
Not provided
Not provided
|
|
| Not Hispanic or Latino |
|
|
| Unknown |
|
|
| Not Reported |
|
|
|
| Black/African American |
|
|
| Asian |
|
|
| Multiple |
|
|
| Not Reported |
|
|
|
|
|
|
|
|
|
|
| OG001 | Imetelstat 9.4 mg/kg | Participants received imetelstat 9.4 mg/kg of body weight as intravenous infusion on Day 1 of each 21-day cycle until disease progression, unacceptable toxicity, or study end. After the end of the main study, participants who were receiving benefit from study treatment opted to continue to receive imetelstat during the Extension Phase until there is loss of benefit or unacceptable toxicity. (Maximum duration on study was approximately 2.3 years and Maximum duration on extension phase was approximately 1.8 years). |
|
|
| OG001 | Imetelstat 9.4 mg/kg | Participants received imetelstat 9.4 mg/kg of body weight as intravenous infusion on Day 1 of each 21-day cycle until disease progression, unacceptable toxicity, or study end. After the end of the main study, participants who were receiving benefit from study treatment opted to continue to receive imetelstat during the Extension Phase until there is loss of benefit or unacceptable toxicity. (Maximum duration on study was approximately 2.3 years and Maximum duration on extension phase was approximately 1.8 years). |
|
|
| OG001 | Imetelstat 9.4 mg/kg | Participants received imetelstat 9.4 mg/kg of body weight as intravenous infusion on Day 1 of each 21-day cycle until disease progression, unacceptable toxicity, or study end. After the end of the main study, participants who were receiving benefit from study treatment opted to continue to receive imetelstat during the Extension Phase until there is loss of benefit or unacceptable toxicity. (Maximum duration on study was approximately 2.3 years and Maximum duration on extension phase was approximately 1.8 years). |
|
|
| OG001 | Imetelstat 9.4 mg/kg | Participants received imetelstat 9.4 mg/kg of body weight as intravenous infusion on Day 1 of each 21-day cycle until disease progression, unacceptable toxicity, or study end. After the end of the main study, participants who were receiving benefit from study treatment opted to continue to receive imetelstat during the Extension Phase until there is loss of benefit or unacceptable toxicity. (Maximum duration on study was approximately 2.3 years and Maximum duration on extension phase was approximately 1.8 years). |
|
|
| OG001 | Imetelstat 9.4 mg/kg | Participants received imetelstat 9.4 mg/kg of body weight as intravenous infusion on Day 1 of each cycle (each cycle was of 21 days) until disease progression, unacceptable toxicity, or study end. After the end of the main study, Participants who were receiving benefit from study treatment opted to continue to receive imetelstat during the Extension Phase until there is loss of benefit or unacceptable toxicity. (Maximum duration on study was approximately 2.3 years and Maximum duration on extension phase was approximately 1.8 years). |
|
|
| OG001 | Imetelstat 9.4 mg/kg | Participants received imetelstat 9.4 mg/kg of body weight as intravenous infusion on Day 1 of each 21-day cycle until disease progression, unacceptable toxicity, or study end. After the end of the main study, participants who were receiving benefit from study treatment opted to continue to receive imetelstat during the Extension Phase until there is loss of benefit or unacceptable toxicity. (Maximum duration on study was approximately 2.3 years and Maximum duration on extension phase was approximately 1.8 years). |
|
|
| OG001 | Imetelstat 9.4 mg/kg | Participants received imetelstat 9.4 mg/kg of body weight as intravenous infusion on Day 1 of each 21-day cycle until disease progression, unacceptable toxicity, or study end. After the end of the main study, participants who were receiving benefit from study treatment opted to continue to receive imetelstat during the Extension Phase until there is loss of benefit or unacceptable toxicity. (Maximum duration on study was approximately 2.3 years and Maximum duration on extension phase was approximately 1.8 years). |
|
|
| OG001 | Imetelstat 9.4 mg/kg | Participants received imetelstat 9.4 mg/kg of body weight as intravenous infusion on Day 1 of each 21-day cycle until disease progression, unacceptable toxicity, or study end. After the end of the main study, participants who were receiving benefit from study treatment opted to continue to receive imetelstat during the Extension Phase until there is loss of benefit or unacceptable toxicity. (Maximum duration on study was approximately 2.3 years and Maximum duration on extension phase was approximately 1.8 years). |
|
|
|
|
| OG001 | Imetelstat 9.4 mg/kg | Participants received imetelstat 9.4 mg/kg of body weight as intravenous infusion on Day 1 of each 21-day cycle until disease progression, unacceptable toxicity, or study end. After the end of the main study, participants who were receiving benefit from study treatment opted to continue to receive imetelstat during the Extension Phase until there is loss of benefit or unacceptable toxicity. (Maximum duration on study was approximately 2.3 years and Maximum duration on extension phase was approximately 1.8 years). |
|
|
| OG001 | Imetelstat 9.4 mg/kg | Participants received imetelstat 9.4 mg/kg of body weight as intravenous infusion on Day 1 of each 21-day cycle until disease progression, unacceptable toxicity, or study end. After the end of the main study, participants who were receiving benefit from study treatment opted to continue to receive imetelstat during the Extension Phase until there is loss of benefit or unacceptable toxicity. (Maximum duration on study was approximately 2.3 years and Maximum duration on extension phase was approximately 1.8 years). |
|
|
| OG001 | Imetelstat 9.4 mg/kg | Participants received imetelstat 9.4 mg/kg of body weight as intravenous infusion on Day 1 of each 21-day cycle until disease progression, unacceptable toxicity, or study end. After the end of the main study, participants who were receiving benefit from study treatment opted to continue to receive imetelstat during the Extension Phase until there is loss of benefit or unacceptable toxicity. (Maximum duration on study was approximately 2.3 years and Maximum duration on extension phase was approximately 1.8 years). |
|
|
Participants received imetelstat 9.4 mg/kg of body weight as intravenous infusion on Day 1 of each 21-day cycle until disease progression, unacceptable toxicity, or study end. After the end of the main study, participants who were receiving benefit from study treatment opted to continue to receive imetelstat during the Extension Phase until there is loss of benefit or unacceptable toxicity. (Maximum duration on study was approximately 2.3 years and Maximum duration on extension phase was approximately 1.8 years). |
|
|
Participants received imetelstat 9.4 mg/kg of body weight as intravenous infusion on Day 1 of each 21-day cycle until disease progression, unacceptable toxicity, or study end. After the end of the main study, participants who were receiving benefit from study treatment opted to continue to receive imetelstat during the Extension Phase until there is loss of benefit or unacceptable toxicity. (Maximum duration on study was approximately 2.3 years and Maximum duration on extension phase was approximately 1.8 years).
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