Study to Evaluate Activity of 2 Dose Levels of Imetelstat in Participants With Intermediate-2 or High-Risk Myelofibrosis (MF) Previously Treated With Janus Kinase (JAK) Inhibitor

• Sponsor: Geron Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02426086
• Collaborator: (none)
• Enrollment: 107
• Locations: 72
• Arms: 2
• Actual Duration (Months): 53.4
• Patients Per Site: 1.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Myelofibrosis	Drug: Imetelstat 4.7 mg/kg; Drug: Imetelstat 9.4 mg/kg	Phase 2

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 107 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Masking Description: Initially single-blind; treatments unmasked after 1st Interim Analysis and continued as open-label treatment.
• Primary Purpose: Treatment
• Official Title: A Randomized, Single-Blind, Multicenter Phase 2 Study to Evaluate the Activity of 2 Dose Levels of Imetelstat in Subjects With Intermediate-2 or High-Risk Myelofibrosis (MF) Relapsed/Refractory to Janus Kinase (JAK) Inhibitor
• Actual Study Start Date: Aug 28, 2015
• Actual Primary Completion Date: Apr 26, 2018
• Actual Study Completion Date: Feb 7, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Imetelstat 4.7 mg/kg	Drug: 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. Study drug was administered intravenously until disease progression, unacceptable toxicity, or study end.
Experimental: Imetelstat 9.4 mg/kg	Drug: 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.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Spleen Response [Week 24]

   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).

2. Percentage of Participants With Symptom Response [Week 24]

   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.

Secondary Outcome Measures

1. Percentage of Participants With Overall Response as Per Modified 2013 International Working Group - Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) Criteria [Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years)]

   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.

2. Percentage of Participants With Clinical Improvement (CI) Per Modified 2013 IWG-MRT Criteria [Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years)]

   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.

3. Percentage of Participants With Clinical Response Per Modified 2013 IWG-MRT [Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years)]

   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.

4. Percentage of Participants With Spleen Response Per Modified 2013 IWG-MRT Criteria [Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years)]

   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.

5. Percentage of Participants With Symptoms Response Per Modified 2013 IWG-MRT Criteria [Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years)]

   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.

6. Percentage of Participants With Anemia Response Per Modified 2013 IWG-MRT Criteria [Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years)]

   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.

7. Duration of Response (PR/CI/RWCI) as Per IWG-MRT Criteria [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)]

   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.

8. Overall Survival [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)]

   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.

9. 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 [Up to end of the treatment (approximately up to 2.3 years)]

   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.

10. EuroQol 5 Dimension 5 Level (EQ-5D-5L): Utility Score and Visual Analog Scale (VAS) [At the end of treatment, up to approximately 2.3 years]

    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.

11. Percentage of Participants With Clinically Meaningful Improvement in Brief Pain Inventory (BPI) [Up to end of treatment (approximately up to 2.3 years)]

    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.

12. Patient's Global Impression of Change (PGIC) [At the end of treatment, up to approximately 2.3 years]

    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).

13. Number of Participants With Treatment-emergent Adverse Events (TEAEs) [Up to end of extension phase (approximately up to 4.2 years)]

    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.

14. 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)]

15. 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)]

16. 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)]

17. 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)]

18. Elimination Half-Life (t1/2) 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 (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).

19. 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)]

20. 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)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of primary myelofibrosis (PMF) according to the revised WHO criteria; or post-essential thrombocythemia-myelofibrosis (PET-MF) or post-polycythemia vera-myelofibrosis (PPV-MF) according to the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria.

• Dynamic International Prognostic Scoring System (DIPSS) intermediate-2 or highrisk MF.

• Measurable splenomegaly prior to study entry as demonstrated by palpable spleen measuring ≥ 5 cm below the left costal margin OR spleen volume of ≥ 450 cm^3 measured by magnetic resonance imaging (MRI).

• Active symptoms of MF as demonstrated by a symptom score of at least 5 points (on a 0 to 10 scale) on at least one of the symptoms or a score of 3 or greater on at least 2 of the symptoms.

• Documented progressive disease during or after Janus kinase (JAK) inhibitor therapy.

• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2.

Exclusion Criteria:

• Peripheral blood blast count of ≥ 10% or bone marrow blast count of ≥ 10%.

• Prior treatment with imetelstat.

• Any chemotherapy or MF-directed therapy, investigational drug, hydroxyurea, immunomodulatory or immunosuppressive therapy, corticosteroids or JAK inhibitor therapy ≤14 days prior to randomization.

• Major surgery within 4 weeks prior to randomization.

• Active systemic hepatitis infection requiring treatment (carriers of hepatitis virus are permitted to enter the study), of any type or known acute or chronic liver disease including cirrhosis.

• Prior history of hematopoietic stem cell transplant.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States
2		Duarte	California	United States
3		La Jolla	California	United States
4		Los Angeles	California	United States
5		Stanford	California	United States
6		Washington	District of Columbia	United States
7		Tampa	Florida	United States
8		West Palm Beach	Florida	United States
9		Chicago	Illinois	United States
10		Louisville	Kentucky	United States
11		Baltimore	Maryland	United States
12		Ann Arbor	Michigan	United States
13		Rochester	Minnesota	United States
14		Saint Louis	Missouri	United States
15		Bronx	New York	United States
16		Buffalo	New York	United States
17		Lake Success	New York	United States
18		New York	New York	United States
19		Charlotte	North Carolina	United States
20		Durham	North Carolina	United States
21		Winston-Salem	North Carolina	United States
22		Cincinnati	Ohio	United States
23		Philadelphia	Pennsylvania	United States
24		Greenville	South Carolina	United States
25		Watertown	South Dakota	United States
26		Nashville	Tennessee	United States
27		Dallas	Texas	United States
28		Seattle	Washington	United States
29		Milwaukee	Wisconsin	United States
30		Antwerpen		Belgium
31		Brugge		Belgium
32		Brussel		Belgium
33		Leuven		Belgium
34		Edmonton	Alberta	Canada
35		Winnipeg	Manitoba	Canada
36		Montreal	Quebec	Canada
37		Angers		France
38		Lille		France
39		Marseille Cedex 9		France
40		Paris		France
41		Pierre Benite		France
42		Toulouse cedex 9		France
43		Aachen		Germany
44		Dresden		Germany
45		Duesseldorf		Germany
46		Frankfurt		Germany
47		Hamburg		Germany
48		Heidelberg		Germany
49		Koeln		Germany
50		Leipzig		Germany
51		Mannheim		Germany
52		Rostock		Germany
53		Haifa		Israel
54		Jerusalem		Israel
55		Kfar Saba		Israel
56		Nahariya		Israel
57		Ramat Gan		Israel
58		Tel Aviv		Israel
59		Bergamo		Italy
60		Bologna		Italy
61		Seoul		Korea, Republic of
62		Barcelona		Spain
63		Las Palmas De Gran Canaria		Spain
64		Madrid		Spain
65		Salamanca		Spain
66		Valencia		Spain
67		Chiayi City		Taiwan
68		Taipei		Taiwan
69		Birmingham		United Kingdom
70		Glasgow		United Kingdom
71		London		United Kingdom
72		Oxford		United Kingdom

Sponsors and Collaborators

• Geron Corporation

Investigators

• Study Director: Study Clinical Team, Geron Corporation

Study Documents (Full-Text)

• Study Protocol - Mar 28, 2019
• Statistical Analysis Plan - May 14, 2018

More Information

Publications

None provided.

• Responsible Party: Geron Corporation
• ClinicalTrials.gov Identifier: NCT02426086
• Other Study ID Numbers: CR107170; 63935937MYF2001; 2015-000946-41
• First Posted: Apr 24, 2015
• Last Update Posted: Sep 14, 2021
• Last Verified: Aug 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Keywords provided by Geron Corporation: Myelofibrosis; Imetelstat; GRN163L; Relapsed/refractory to JAKi; IMbark
• Additional relevant MeSH terms: Primary Myelofibrosis; Niacinamide; Imetelstat; Motesanib diphosphate

Study Results

Participant Flow

Recruitment Details

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.

Pre-assignment Detail

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).

Arm/Group Title	Imetelstat 4.7 mg/kg	Imetelstat 9.4 mg/kg
Arm/Group Description	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).	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).
Period Title: Overall Study
STARTED	48	59
Treated	48	59
COMPLETED	0	0
NOT COMPLETED	48	59

Baseline Characteristics

Arm/Group Title	Imetelstat 4.7 mg/kg	Imetelstat 9.4 mg/kg	Total
Arm/Group Description	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).	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).	Total of all reporting groups
Overall Participants	48	59	107
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.0 (8.95)	66.5 (9.39)	67.2 (9.18)
Sex: Female, Male (Count of Participants)
Female	16 33.3%	24 40.7%	40 37.4%
Male	32 66.7%	35 59.3%	67 62.6%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	2 4.2%	8 13.6%	10 9.3%
Not Hispanic or Latino	41 85.4%	44 74.6%	85 79.4%
Unknown	2 4.2%	3 5.1%	5 4.7%
Not Reported	3 6.3%	4 6.8%	7 6.5%
Race/Ethnicity, Customized (Count of Participants)
White	40 83.3%	48 81.4%	88 82.2%
Black/African American	2 4.2%	2 3.4%	4 3.7%
Asian	2 4.2%	3 5.1%	5 4.7%
Multiple	1 2.1%	0 0%	1 0.9%
Not Reported	3 6.3%	6 10.2%	9 8.4%
Region (Count of Participants)
United States/Canada	25 52.1%	18 30.5%	43 40.2%
European Union	19 39.6%	34 57.6%	53 49.5%
Rest of World	4 8.3%	7 11.9%	11 10.3%
Spleen Size by Palpation (centimeter (cm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeter (cm)]	17.6 (7.62)	17.3 (7.51)	17.4 (7.53)
Platelet Count (Count of Participants)
<75 (10^9/L)	1 2.1%	2 3.4%	3 2.8%
75 - <150 (10^9/L)	23 47.9%	31 52.5%	54 50.5%
≥150 (10^9/L)	24 50%	26 44.1%	50 46.7%
Eastern Cooperative Oncology Group (ECOG) Score (Count of Participants)
0: Asymptomatic	11 22.9%	14 23.7%	25 23.4%
1: Symptomatic fully ambulatory	26 54.2%	34 57.6%	60 56.1%
2: Self care	11 22.9%	11 18.6%	22 20.6%
Time from Last JAKi Treatment (months) [Median (Full Range) ]
Median (Full Range) [months]	1.4	1.7	1.7
Duration of Prior JAKi Treatment (months) [Median (Full Range) ]
Median (Full Range) [months]	22.3	24.5	23.0
Dynamic International Prognostic Scoring System (DIPSS) (Count of Participants)
Intermediate 2	28 58.3%	34 57.6%	62 57.9%
High Risk	19 39.6%	25 42.4%	44 41.1%
Missing	1 2.1%	0 0%	1 0.9%
Type of Myelofibrosis (MF) (Count of Participants)
Primary MF (PMF)	27 56.3%	36 61%	63 58.9%
Post Essential Thrombocythemia (PET)	9 18.8%	10 16.9%	19 17.8%
Post Polycythemia Vera (PPV)	12 25%	13 22%	25 23.4%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Spleen Response
Description	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).
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Treated analysis set included all participants who received at least 1 dose of study drug.

Arm/Group Title	Imetelstat 4.7 mg/kg	Imetelstat 9.4 mg/kg
Arm/Group Description	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).	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).
Measure Participants	48	59
Number (95% Confidence Interval) [percentage of participants]	0 0%	10.2 17.3%

2. Primary Outcome

Title	Percentage of Participants With Symptom Response
Description	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.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Treated analysis set included all participants who received at least 1 dose of study drug.

Arm/Group Title	Imetelstat 4.7 mg/kg	Imetelstat 9.4 mg/kg
Arm/Group Description	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).	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).
Measure Participants	48	59
Number (95% Confidence Interval) [percentage of participants]	6.3 13.1%	32.2 54.6%

3. Secondary Outcome

Title	Percentage of Participants With Overall Response as Per Modified 2013 International Working Group - Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) Criteria
Description	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.
Time Frame	Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years)

Outcome Measure Data

Analysis Population Description

Treated analysis set included all participants who received at least 1 dose of study drug.

Arm/Group Title	Imetelstat 4.7 mg/kg	Imetelstat 9.4 mg/kg
Arm/Group Description	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).	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).
Measure Participants	48	59
Number (95% Confidence Interval) [percentage of participants]	0 0%	1.7 2.9%

4. Secondary Outcome

Title	Percentage of Participants With Clinical Improvement (CI) Per Modified 2013 IWG-MRT Criteria
Description	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.
Time Frame	Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years)

Outcome Measure Data

Analysis Population Description

Treated analysis set included all participants who received at least 1 dose of study drug.

Arm/Group Title	Imetelstat 4.7 mg/kg	Imetelstat 9.4 mg/kg
Arm/Group Description	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).	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).
Measure Participants	48	59
Number [percentage of participants]	16.7 34.8%	25.4 43.1%

5. Secondary Outcome

Title	Percentage of Participants With Clinical Response Per Modified 2013 IWG-MRT
Description	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.
Time Frame	Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years)

Outcome Measure Data

Analysis Population Description

Treated analysis set included all participants who received at least 1 dose of study drug.

Arm/Group Title	Imetelstat 4.7 mg/kg	Imetelstat 9.4 mg/kg
Arm/Group Description	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).	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).
Measure Participants	48	59
Number (95% Confidence Interval) [percentage of participants]	16.7 34.8%	27.1 45.9%

6. Secondary Outcome

Title	Percentage of Participants With Spleen Response Per Modified 2013 IWG-MRT Criteria
Description	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.
Time Frame	Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years)

Outcome Measure Data

Analysis Population Description

Treated analysis set included all participants who received at least 1 dose of study drug. All treated participants were evaluated for each response.

Arm/Group Title	Imetelstat 4.7 mg/kg	Imetelstat 9.4 mg/kg
Arm/Group Description	Participants received imetelstat 4.7 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. Participants had an option to continue the treatment at the current dose or escalated dose of 9.4 mg/kg based on 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).	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).
Measure Participants	48	59
Spleen response with CI	0 0%	3.4 5.8%
Spleen response without CI	2.1 4.4%	0 0%

7. Secondary Outcome

Title	Percentage of Participants With Symptoms Response Per Modified 2013 IWG-MRT Criteria
Description	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.
Time Frame	Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years)

Outcome Measure Data

Analysis Population Description

Treated analysis set included all participants who received at least 1 dose of study drug. All treated participants were evaluated for each response.

Arm/Group Title	Imetelstat 4.7 mg/kg	Imetelstat 9.4 mg/kg
Arm/Group Description	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).	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).
Measure Participants	48	59
Symptom response with CI	14.6 30.4%	22.0 37.3%
Symptom response without CI	4.2 8.8%	8.5 14.4%

8. Secondary Outcome

Title	Percentage of Participants With Anemia Response Per Modified 2013 IWG-MRT Criteria
Description	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.
Time Frame	Every 12 weeks up to Week 48 then every 24 weeks (approximately up to 2.3 years)

Outcome Measure Data

Analysis Population Description

Treated analysis set included all participants who received at least 1 dose of study drug. All treated participants were evaluated for each response.

Arm/Group Title	Imetelstat 4.7 mg/kg	Imetelstat 9.4 mg/kg
Arm/Group Description	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).	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).
Measure Participants	48	59
Anemia response with CI	4.2 8.8%	6.8 11.5%
Anemia response without CI	0 0%	1.7 2.9%

9. Secondary Outcome

Title	Duration of Response (PR/CI/RWCI) as Per IWG-MRT Criteria
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Imetelstat 4.7 mg/kg	Imetelstat 9.4 mg/kg
Arm/Group Description	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).	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).
Measure Participants	11	21
Median (95% Confidence Interval) [weeks]	36.3	38.3

10. Secondary Outcome

Title	Overall Survival
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

Treated analysis set included all participants who received at least 1 dose of study drug.

Arm/Group Title	Imetelstat 4.7 mg/kg	Imetelstat 9.4 mg/kg
Arm/Group Description	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).	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).
Measure Participants	48	59
Median (95% Confidence Interval) [months]	19.91	28.09

11. Secondary Outcome

Title	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
Description	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.
Time Frame	Up to end of the treatment (approximately up to 2.3 years)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Imetelstat 4.7 mg/kg	Imetelstat 9.4 mg/kg
Arm/Group Description	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).	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).
Measure Participants	18	33
Number [percentage of participants]	22.2 46.3%	36.4 61.7%

12. Secondary Outcome

Title	EuroQol 5 Dimension 5 Level (EQ-5D-5L): Utility Score and Visual Analog Scale (VAS)
Description	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.
Time Frame	At the end of treatment, up to approximately 2.3 years

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Imetelstat 4.7 mg/kg	Imetelstat 9.4 mg/kg
Arm/Group Description	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).	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).
Measure Participants	18	33
EQ-5D-5L: Utility Score	0.498 (0.2999)	0.626 (0.2117)
EQ-5D-5L: VAS	51.28 (21.143)	47.73 (16.398)

13. Secondary Outcome

Title	Percentage of Participants With Clinically Meaningful Improvement in Brief Pain Inventory (BPI)
Description	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.
Time Frame	Up to end of treatment (approximately up to 2.3 years)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Imetelstat 4.7 mg/kg	Imetelstat 9.4 mg/kg
Arm/Group Description	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).	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).
Measure Participants	18	33
Pain at its Worst: Improvement	50.0 104.2%	75.8 128.5%
Pain at its Least: Improvement	44.4 92.5%	51.5 87.3%
Pain on the Average: Improvement	55.6 115.8%	66.7 113.1%
Pain Right Now: Improvement	61.1 127.3%	66.7 113.1%
Relief Pain Treatments Provided: Improvement	50.0 104.2%	53.1 90%
Pain Interfered General Activity: Improvement	72.2 150.4%	68.8 116.6%
Pain Interfered with Mood: Improvement	50.0 104.2%	59.4 100.7%
Pain Interfered Walking Ability: Improvement	38.9 81%	78.1 132.4%
Pain Interfered with Normal Work: Improvement	61.1 127.3%	62.5 105.9%
Pain Interfered with Relations: Improvement	44.4 92.5%	53.1 90%
Pain Interfered with Sleep: Improvement	61.1 127.3%	78.1 132.4%
Pain Interfered Enjoyment of Life: Improvement	61.1 127.3%	62.5 105.9%

14. Secondary Outcome

Title	Patient's Global Impression of Change (PGIC)
Description	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).
Time Frame	At the end of treatment, up to approximately 2.3 years

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Imetelstat 4.7 mg/kg	Imetelstat 9.4 mg/kg
Arm/Group Description	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).	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).
Measure Participants	17	33
Mean (Standard Deviation) [score on a scale]	4.82 (1.237)	3.97 (1.571)

15. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Description	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.
Time Frame	Up to end of extension phase (approximately up to 4.2 years)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study treatment.

Arm/Group Title	Imetelstat 4.7 mg/kg	Imetelstat 9.4 mg/kg
Arm/Group Description	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).	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).
Measure Participants	48	59
Count of Participants [Participants]	47 97.9%	59 100%

16. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Imetelstat
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PK: Imetelstat 4.7 mg/kg	PK: Imetelstat 9.4 mg/kg
Arm/Group Description	Participants received imetelstat 4.7 mg/kg of body weight as intravenous infusion on Day 1 of cycle 1 and those who had serial PK samples collected.	Participants received imetelstat 9.4 mg/kg of body weight as intravenous infusion on Day 1 of cycle 1 and those who had serial PK samples collected.
Measure Participants	11	17
Mean (Standard Deviation) [μg/mL]	57.0 (72.3)	81.9 (40.0)

17. Secondary Outcome

Title	Time to Reach Maximum Observed Plasma Concentration (Tmax) of Imetelstat
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PK: Imetelstat 4.7 mg/kg	PK: Imetelstat 9.4 mg/kg
Arm/Group Description	Participants received imetelstat 4.7 mg/kg of body weight as intravenous infusion on Day 1 of cycle 1 and those who had serial PK samples collected.	Participants received imetelstat 9.4 mg/kg of body weight as intravenous infusion on Day 1 of cycle 1 and those who had serial PK samples collected.
Measure Participants	11	17
Median (Full Range) [hr]	2.00	2.00

18. Secondary Outcome

Title	Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC 0-24) of Imetelstat
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PK: Imetelstat 4.7 mg/kg	PK: Imetelstat 9.4 mg/kg
Arm/Group Description	Participants received imetelstat 4.7 mg/kg of body weight as intravenous infusion on Day 1 of cycle 1 and those who had serial PK samples collected.	Participants received imetelstat 9.4 mg/kg of body weight as intravenous infusion on Day 1 of cycle 1 and those who had serial PK samples collected.
Measure Participants	11	17
Mean (Standard Deviation) [μg*hr/mL]	171 (135)	501 (283)

19. Secondary Outcome

Title	Area Under the Plasma Concentration-Time Profile From Time Zero to Infinity (AUC0-inf) of Imetelstat
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PK: Imetelstat 4.7 mg/kg	PK: Imetelstat 9.4 mg/kg
Arm/Group Description	Participants received imetelstat 4.7 mg/kg of body weight as intravenous infusion on Day 1 of cycle 1 and those who had serial PK samples collected.	Participants received imetelstat 9.4 mg/kg of body weight as intravenous infusion on Day 1 of cycle 1 and those who had serial PK samples collected.
Measure Participants	11	17
Mean (Standard Deviation) [μg*h/mL]	193 (156)	524 (297)

20. Secondary Outcome

Title	Elimination Half-Life (t1/2) of Imetelstat
Description	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).
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PK: Imetelstat 4.7 mg/kg	PK: Imetelstat 9.4 mg/kg
Arm/Group Description	Participants received imetelstat 4.7 mg/kg of body weight as intravenous infusion on Day 1 of cycle 1 and those who had serial PK samples collected.	Participants received imetelstat 9.4 mg/kg of body weight as intravenous infusion on Day 1 of cycle 1 and those who had serial PK samples collected.
Measure Participants	11	17
Mean (Standard Deviation) [hr]	4.6 (1.6)	5.5 (1.5)

21. Secondary Outcome

Title	Total Systemic Clearance (CL) of Imetelstat
Time Frame	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)

Outcome Measure Data

Analysis Population Description

PK subset included all participants who had serial PK sampling during cycle 1 treatment to determine the CL of Imetelstat by noncompartmental PK analysis.

Arm/Group Title	PK: Imetelstat 4.7 mg/kg	PK: Imetelstat 9.4 mg/kg
Arm/Group Description	Participants received imetelstat 4.7 mg/kg of body weight as intravenous infusion on Day 1 of cycle 1 and those who had serial PK samples collected.	Participants received imetelstat 9.4 mg/kg of body weight as intravenous infusion on Day 1 of cycle 1 and those who had serial PK samples collected.
Measure Participants	11	17
Mean (Standard Deviation) [L/hr/kg]	0.0329 (0.0138)	0.0252 (0.0157)

22. Secondary Outcome

Title	Volume of Distribution (Vd) of Imetelstat
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PK: Imetelstat 4.7 mg/kg	PK: Imetelstat 9.4 mg/kg
Arm/Group Description	Participants received imetelstat 4.7 mg/kg of body weight as intravenous infusion on Day 1 of cycle 1 and those who had serial PK samples collected.	Participants received imetelstat 9.4 mg/kg of body weight as intravenous infusion on Day 1 of cycle 1 and those who had serial PK samples collected.
Measure Participants	11	17
Mean (Standard Deviation) [L/kg]	0.198 (0.0770)	0.190 (0.104)

Adverse Events

Time Frame	Up to end of extension phase (approximately up to 4.2 years)
Adverse Event Reporting Description	Safety analysis set included all participants who received at least 1 dose of study treatment.
Arm/Group Title	Imetelstat 4.7 mg/kg		Imetelstat 9.4 mg/kg		Imetelstat Dose Escalated From 4.7 mg/kg to 9.4 mg/kg
Arm/Group Description	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.		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 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.
All Cause Mortality
	Imetelstat 4.7 mg/kg		Imetelstat 9.4 mg/kg		Imetelstat Dose Escalated From 4.7 mg/kg to 9.4 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/48 (70.8%)		36/59 (61%)		1/12 (8.3%)
Serious Adverse Events
	Imetelstat 4.7 mg/kg		Imetelstat 9.4 mg/kg		Imetelstat Dose Escalated From 4.7 mg/kg to 9.4 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/48 (50%)		21/59 (35.6%)		4/12 (33.3%)
Blood and lymphatic system disorders
Anaemia	0/48 (0%)		2/59 (3.4%)		0/12 (0%)
Bone marrow failure	0/48 (0%)		1/59 (1.7%)		0/12 (0%)
Febrile neutropenia	1/48 (2.1%)		1/59 (1.7%)		0/12 (0%)
Haemolysis	0/48 (0%)		1/59 (1.7%)		0/12 (0%)
Leukocytosis	1/48 (2.1%)		0/59 (0%)		0/12 (0%)
Pancytopenia	0/48 (0%)		1/59 (1.7%)		0/12 (0%)
Splenic artery thrombosis	1/48 (2.1%)		0/59 (0%)		0/12 (0%)
Splenic infarction	2/48 (4.2%)		0/59 (0%)		0/12 (0%)
Splenic vein thrombosis	1/48 (2.1%)		0/59 (0%)		0/12 (0%)
Splenomegaly	1/48 (2.1%)		1/59 (1.7%)		0/12 (0%)
Thrombocytopenia	1/48 (2.1%)		1/59 (1.7%)		0/12 (0%)
Cardiac disorders
Cardiac failure	1/48 (2.1%)		1/59 (1.7%)		0/12 (0%)
Cardiac failure congestive	1/48 (2.1%)		0/59 (0%)		0/12 (0%)
Cardiac tamponade	0/48 (0%)		1/59 (1.7%)		0/12 (0%)
Gastrointestinal disorders
Abdominal pain	2/48 (4.2%)		0/59 (0%)		0/12 (0%)
Ascites	0/48 (0%)		1/59 (1.7%)		0/12 (0%)
Diarrhoea	1/48 (2.1%)		0/59 (0%)		0/12 (0%)
Melaena	0/48 (0%)		2/59 (3.4%)		0/12 (0%)
Rectal haemorrhage	0/48 (0%)		1/59 (1.7%)		0/12 (0%)
Vomiting	1/48 (2.1%)		1/59 (1.7%)		0/12 (0%)
General disorders
Chills	1/48 (2.1%)		1/59 (1.7%)		0/12 (0%)
Fatigue	0/48 (0%)		2/59 (3.4%)		0/12 (0%)
Non-cardiac chest pain	1/48 (2.1%)		0/59 (0%)		0/12 (0%)
Oedema peripheral	0/48 (0%)		1/59 (1.7%)		0/12 (0%)
Hepatobiliary disorders
Hepatic failure	0/48 (0%)		1/59 (1.7%)		0/12 (0%)
Hepatic function abnormal	1/48 (2.1%)		0/59 (0%)		0/12 (0%)
Infections and infestations
Bacterial infection	0/48 (0%)		1/59 (1.7%)		0/12 (0%)
Bronchitis	1/48 (2.1%)		0/59 (0%)		0/12 (0%)
Cellulitis	1/48 (2.1%)		0/59 (0%)		1/12 (8.3%)
Escherichia bacteraemia	1/48 (2.1%)		0/59 (0%)		0/12 (0%)
Listeriosis	0/48 (0%)		1/59 (1.7%)		0/12 (0%)
Lung infection	1/48 (2.1%)		0/59 (0%)		0/12 (0%)
Ophthalmic herpes zoster	0/48 (0%)		1/59 (1.7%)		0/12 (0%)
Pneumonia	2/48 (4.2%)		1/59 (1.7%)		0/12 (0%)
Pneumonia klebsiella	0/48 (0%)		1/59 (1.7%)		0/12 (0%)
Respiratory tract infection	0/48 (0%)		1/59 (1.7%)		0/12 (0%)
Sepsis	1/48 (2.1%)		0/59 (0%)		0/12 (0%)
Upper respiratory tract infection	0/48 (0%)		1/59 (1.7%)		0/12 (0%)
Urinary tract infection	1/48 (2.1%)		0/59 (0%)		1/12 (8.3%)
Injury, poisoning and procedural complications
Head injury	1/48 (2.1%)		0/59 (0%)		0/12 (0%)
Investigations
Aspartate aminotransferase increased	0/48 (0%)		1/59 (1.7%)		0/12 (0%)
Metabolism and nutrition disorders
Failure to thrive	0/48 (0%)		1/59 (1.7%)		0/12 (0%)
Fluid overload	0/48 (0%)		1/59 (1.7%)		0/12 (0%)
Gout	1/48 (2.1%)		0/59 (0%)		0/12 (0%)
Hyperkalaemia	0/48 (0%)		1/59 (1.7%)		0/12 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/48 (0%)		1/59 (1.7%)		0/12 (0%)
Musculoskeletal pain	0/48 (0%)		1/59 (1.7%)		0/12 (0%)
Rotator cuff syndrome	0/48 (0%)		0/59 (0%)		1/12 (8.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelofibrosis	0/48 (0%)		0/59 (0%)		1/12 (8.3%)
Nervous system disorders
Cerebral haemorrhage	0/48 (0%)		0/59 (0%)		1/12 (8.3%)
Encephalopathy	0/48 (0%)		0/59 (0%)		1/12 (8.3%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/48 (0%)		1/59 (1.7%)		0/12 (0%)
Dyspnoea	4/48 (8.3%)		1/59 (1.7%)		1/12 (8.3%)
Pleural effusion	0/48 (0%)		1/59 (1.7%)		0/12 (0%)
Pulmonary congestion	1/48 (2.1%)		0/59 (0%)		0/12 (0%)
Pulmonary hypertension	0/48 (0%)		1/59 (1.7%)		0/12 (0%)
Pulmonary oedema	1/48 (2.1%)		0/59 (0%)		0/12 (0%)
Vascular disorders
Aneurysm ruptured	0/48 (0%)		1/59 (1.7%)		0/12 (0%)
Haematoma	1/48 (2.1%)		0/59 (0%)		0/12 (0%)
Haemorrhage	0/48 (0%)		1/59 (1.7%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Imetelstat 4.7 mg/kg		Imetelstat 9.4 mg/kg		Imetelstat Dose Escalated From 4.7 mg/kg to 9.4 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	47/48 (97.9%)		59/59 (100%)		12/12 (100%)
Blood and lymphatic system disorders
Anaemia	15/48 (31.3%)		26/59 (44.1%)		5/12 (41.7%)
Leukocytosis	3/48 (6.3%)		2/59 (3.4%)		0/12 (0%)
Leukopenia	3/48 (6.3%)		8/59 (13.6%)		2/12 (16.7%)
Neutropenia	5/48 (10.4%)		21/59 (35.6%)		3/12 (25%)
Splenomegaly	0/48 (0%)		3/59 (5.1%)		0/12 (0%)
Thrombocytopenia	11/48 (22.9%)		29/59 (49.2%)		4/12 (33.3%)
Coagulopathy	0/48 (0%)		1/59 (1.7%)		1/12 (8.3%)
Cardiac disorders
Palpitations	2/48 (4.2%)		6/59 (10.2%)		0/12 (0%)
Aortic valve stenosis	0/48 (0%)		1/59 (1.7%)		1/12 (8.3%)
Cardiac failure	0/48 (0%)		0/59 (0%)		1/12 (8.3%)
Ear and labyrinth disorders
Deafness	0/48 (0%)		0/59 (0%)		1/12 (8.3%)
Endocrine disorders
Hypothyroidism	0/48 (0%)		0/59 (0%)		1/12 (8.3%)
Eye disorders
Photophobia	0/48 (0%)		0/59 (0%)		1/12 (8.3%)
Gastrointestinal disorders
Abdominal discomfort	2/48 (4.2%)		5/59 (8.5%)		0/12 (0%)
Abdominal distension	2/48 (4.2%)		4/59 (6.8%)		0/12 (0%)
Abdominal pain	9/48 (18.8%)		14/59 (23.7%)		0/12 (0%)
Abdominal pain upper	2/48 (4.2%)		4/59 (6.8%)		0/12 (0%)
Constipation	9/48 (18.8%)		9/59 (15.3%)		1/12 (8.3%)
Diarrhoea	18/48 (37.5%)		18/59 (30.5%)		3/12 (25%)
Dry mouth	4/48 (8.3%)		1/59 (1.7%)		0/12 (0%)
Dyspepsia	1/48 (2.1%)		3/59 (5.1%)		2/12 (16.7%)
Nausea	15/48 (31.3%)		20/59 (33.9%)		1/12 (8.3%)
Stomatitis	3/48 (6.3%)		2/59 (3.4%)		1/12 (8.3%)
Toothache	0/48 (0%)		3/59 (5.1%)		0/12 (0%)
Vomiting	9/48 (18.8%)		8/59 (13.6%)		1/12 (8.3%)
Aphthous ulcer	0/48 (0%)		1/59 (1.7%)		1/12 (8.3%)
General disorders
Asthenia	9/48 (18.8%)		14/59 (23.7%)		1/12 (8.3%)
Chills	3/48 (6.3%)		8/59 (13.6%)		0/12 (0%)
Fatigue	10/48 (20.8%)		15/59 (25.4%)		1/12 (8.3%)
Malaise	2/48 (4.2%)		3/59 (5.1%)		0/12 (0%)
Oedema peripheral	13/48 (27.1%)		10/59 (16.9%)		3/12 (25%)
Pain	1/48 (2.1%)		3/59 (5.1%)		0/12 (0%)
Pyrexia	8/48 (16.7%)		13/59 (22%)		2/12 (16.7%)
Discomfort	0/48 (0%)		0/59 (0%)		1/12 (8.3%)
Inflammation	0/48 (0%)		0/59 (0%)		1/12 (8.3%)
Peripheral swelling	0/48 (0%)		1/59 (1.7%)		1/12 (8.3%)
Infections and infestations
Nasopharyngitis	0/48 (0%)		6/59 (10.2%)		0/12 (0%)
Rhinovirus infection	0/48 (0%)		3/59 (5.1%)		0/12 (0%)
Upper respiratory tract infection	3/48 (6.3%)		9/59 (15.3%)		1/12 (8.3%)
Urinary tract infection	2/48 (4.2%)		5/59 (8.5%)		1/12 (8.3%)
Bronchitis	1/48 (2.1%)		2/59 (3.4%)		1/12 (8.3%)
Periodontitis	0/48 (0%)		0/59 (0%)		1/12 (8.3%)
Respiratory tract infection	0/48 (0%)		1/59 (1.7%)		2/12 (16.7%)
Sepsis	0/48 (0%)		0/59 (0%)		1/12 (8.3%)
Injury, poisoning and procedural complications
Fall	3/48 (6.3%)		2/59 (3.4%)		0/12 (0%)
Investigations
Blood alkaline phosphatase increased	2/48 (4.2%)		5/59 (8.5%)		0/12 (0%)
Serum ferritin increased	0/48 (0%)		4/59 (6.8%)		0/12 (0%)
Weight decreased	9/48 (18.8%)		8/59 (13.6%)		1/12 (8.3%)
Aspartate aminotransferase increased	1/48 (2.1%)		1/59 (1.7%)		1/12 (8.3%)
Metabolism and nutrition disorders
Decreased appetite	7/48 (14.6%)		10/59 (16.9%)		1/12 (8.3%)
Gout	2/48 (4.2%)		5/59 (8.5%)		0/12 (0%)
Hyperkalaemia	2/48 (4.2%)		4/59 (6.8%)		0/12 (0%)
Hyperuricaemia	3/48 (6.3%)		4/59 (6.8%)		0/12 (0%)
Hypocalcaemia	0/48 (0%)		4/59 (6.8%)		0/12 (0%)
Hypokalaemia	3/48 (6.3%)		0/59 (0%)		0/12 (0%)
Hyponatraemia	3/48 (6.3%)		2/59 (3.4%)		0/12 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	5/48 (10.4%)		7/59 (11.9%)		2/12 (16.7%)
Back pain	5/48 (10.4%)		6/59 (10.2%)		1/12 (8.3%)
Bone pain	4/48 (8.3%)		5/59 (8.5%)		2/12 (16.7%)
Muscle spasms	6/48 (12.5%)		6/59 (10.2%)		0/12 (0%)
Musculoskeletal pain	4/48 (8.3%)		7/59 (11.9%)		1/12 (8.3%)
Myalgia	3/48 (6.3%)		1/59 (1.7%)		0/12 (0%)
Pain in extremity	5/48 (10.4%)		5/59 (8.5%)		1/12 (8.3%)
Chondropathy	0/48 (0%)		0/59 (0%)		1/12 (8.3%)
Flank pain	2/48 (4.2%)		2/59 (3.4%)		1/12 (8.3%)
Limb discomfort	0/48 (0%)		0/59 (0%)		1/12 (8.3%)
Musculoskeletal stiffness	0/48 (0%)		0/59 (0%)		1/12 (8.3%)
Osteonecrosis of jaw	0/48 (0%)		0/59 (0%)		1/12 (8.3%)
Rotator cuff syndrome	0/48 (0%)		0/59 (0%)		1/12 (8.3%)
Nervous system disorders
Dizziness	2/48 (4.2%)		10/59 (16.9%)		1/12 (8.3%)
Headache	6/48 (12.5%)		10/59 (16.9%)		1/12 (8.3%)
Amnesia	0/48 (0%)		0/59 (0%)		1/12 (8.3%)
Cognitive disorder	0/48 (0%)		0/59 (0%)		1/12 (8.3%)
Dysgeusia	1/48 (2.1%)		1/59 (1.7%)		1/12 (8.3%)
Hypoaesthesia	2/48 (4.2%)		0/59 (0%)		2/12 (16.7%)
Psychiatric disorders
Insomnia	6/48 (12.5%)		7/59 (11.9%)		1/12 (8.3%)
Renal and urinary disorders
Renal impairment	1/48 (2.1%)		0/59 (0%)		2/12 (16.7%)
Reproductive system and breast disorders
Genital ulceration	0/48 (0%)		0/59 (0%)		1/12 (8.3%)
Respiratory, thoracic and mediastinal disorders
Cough	11/48 (22.9%)		9/59 (15.3%)		1/12 (8.3%)
Dyspnoea	7/48 (14.6%)		15/59 (25.4%)		1/12 (8.3%)
Epistaxis	3/48 (6.3%)		1/59 (1.7%)		2/12 (16.7%)
Oropharyngeal pain	5/48 (10.4%)		4/59 (6.8%)		0/12 (0%)
Hypoxia	0/48 (0%)		0/59 (0%)		1/12 (8.3%)
Pleural effusion	2/48 (4.2%)		0/59 (0%)		1/12 (8.3%)
Pulmonary fibrosis	0/48 (0%)		0/59 (0%)		1/12 (8.3%)
Respiratory failure	0/48 (0%)		0/59 (0%)		1/12 (8.3%)
Throat irritation	0/48 (0%)		0/59 (0%)		1/12 (8.3%)
Skin and subcutaneous tissue disorders
Ecchymosis	1/48 (2.1%)		4/59 (6.8%)		0/12 (0%)
Erythema	1/48 (2.1%)		5/59 (8.5%)		0/12 (0%)
Hyperhidrosis	2/48 (4.2%)		4/59 (6.8%)		0/12 (0%)
Night sweats	4/48 (8.3%)		4/59 (6.8%)		1/12 (8.3%)
Pruritus	6/48 (12.5%)		8/59 (13.6%)		0/12 (0%)
Pruritus generalised	6/48 (12.5%)		2/59 (3.4%)		1/12 (8.3%)
Rash	3/48 (6.3%)		5/59 (8.5%)		1/12 (8.3%)
Petechiae	1/48 (2.1%)		1/59 (1.7%)		2/12 (16.7%)
Vascular disorders
Hypertension	3/48 (6.3%)		4/59 (6.8%)		0/12 (0%)
Hot flush	0/48 (0%)		0/59 (0%)		1/12 (8.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.