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| ID | Type | Description | Link |
|---|---|---|---|
| CP14B019 | Other Identifier | Janssen Research & Development, LLC |
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This pilot clinical trial studies how well imetelstat sodium works in treating participants with primary or secondary myelofibrosis and other myeloid malignancies. Imetelstat sodium may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES:
I. To evaluate overall response rate.
SECONDARY OBJECTIVES:
I. To evaluate the safety and tolerability of imetelstat (imetelstat sodium) in myelofibrosis (MF).
II. To evaluate the efficacy of imetelstat in the reduction of spleen size, as measured by physical examination (palpable distance from the left costal margin).
III. To evaluate the efficacy of imetelstat in improving anemia or inducing red blood cell transfusion-independence in previously transfusion-dependent participants (per International Working Group for Myelofibrosis Research and Treatment [IWG-MRT] criteria).
IV. To evaluate onset and durability of response as defined in primary and secondary endpoints
EXPLORATORY OBJECTIVES:
I. To evaluate the effect of imetelstat on bone marrow histology, karyotype and JAK2V617F allele burden II. To evaluate the effect of imetelstat on leukocytosis, circulating blast count, circulating immature myeloid cell count and thrombocytosis.
OUTLINE: Participants receive imetelstat sodium intravenously (IV) over 2 hours on day 1. Participants may continue to receive imetelstat study treatment for as long as they derive clinical benefit or until study end. The study end when all participants discontinued study drug, the last participant enrolled has been treated for approximately 5.7 years, or imetelstat is commercially available in the United States, whichever occurs first.
Maximum duration of study was approximately 5.7 years. Arm C was never initiated, and participants allocated to Arm C (Imetelstat 9.4 mg/kg [with MF]) were reassigned to Arms A and B.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A: Imetelstat 9.4 mg/kg (Myelofibrosis [MF]) | Experimental | Participants with MF regardless of spliceosome mutation status or presence of ring sideroblasts received imetelstat 9.4 milligram per kilogram (mg/kg), intravenously (IV) as 2-hour infusion on Day 1 of each 21-day cycle in Core Phase up to 9 cycles. Participants could receive imetelstat beyond Cycle 9 in the Extension Phase if they did not meet any of the withdrawal criteria, did not have disease progression and were receiving clinical benefit from treatment as determined by the investigator. Following treatment discontinuation, participants entered the Event Monitoring Phase for collection of survival status, disease status, and subsequent treatment information (Up to approximately 5.7 years). |
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| Arm B: Imetelstat 9.4 mg/kg as Induction + Maintenance (MF) | Experimental | Participants with MF regardless of spliceosome mutation status or presence of ring sideroblasts received imetelstat 9.4 mg/kg, IV as 2-hour infusion on Days 1, 8, and 15 of 21-day cycle in Cycle 1 followed by 9.4 mg/kg on Day 1 of each 21-day cycle up to 9 cycles in the Core Phase. Participants could receive imetelstat beyond Cycle 9 in the Extension Phase if they did not meet any of the withdrawal criteria, did not have disease progression and were receiving clinical benefit from treatment as determined by the investigator. Following treatment discontinuation, participants entered the Event Monitoring Phase for collection of survival status, disease status, and subsequent treatment information (Up to approximately 5.7 years). |
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| Arm D: Imetelstat 9.4 mg/kg (Blast-phase MF/Acute Myeloid Leukemia) | Experimental | Participants with blast-phase myelofibrosis/acute myeloid leukemia (MF/AML) received imetelstat 9.4 mg/kg, IV as 2-hour infusion weekly on Days 1, 8, 15, 22 of a 28-day cycle up to 9 cycles in the Core Phase. Participants could receive imetelstat beyond Cycle 9 in the Extension Phase if they did not meet any of the withdrawal criteria, did not have disease progression and were receiving clinical benefit from treatment as determined by the investigator. Following treatment discontinuation, participants entered the Event Monitoring Phase for collection of survival status, disease status, and subsequent treatment information (Up to approximately 5.7 years). |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Imetelstat | Drug | Imetelstat sodium administered as IV over 2 hours with treatment as long as participants derive clinical benefit or until end of study. |
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| Measure | Description | Time Frame |
|---|---|---|
| MF Participants: Percentage of Participants With Overall Response (OR) - (Clinical Improvement[CI] or Partial Remission[PR] or Complete Remission[CR]) Per International Working Group - Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) Criteria | OR:CI/PR/CR per IWG-MRT. CR:Bone marrow (BM):<5% blasts;≤Grade 1 MF, AND Peripheral blood:Hemoglobin (Hb) ≥100 g/liter (g/L) and \ | Up to first 9 cycles of treatment (each cycle was of 21 days for Arms A and B and 28 days for Arms E and F) |
| Blastic MF/AML Participants: Percentage of Participants With Overall Response | For this pilot study, overall response was defined as achievement of a leukemic response (i.e. a clinically meaningful reduction in Blast cells). This was quantified as <5% peripheral blood and bone marrow blasts % that lasts for at least two months. Data is reported separately for this arm where response was assessed by this specific criterion. | Up to first 9 cycles of treatment (each cycle was of 28 days for Arm D) |
| MDS Participants: Percentage of Participants With Overall Response (Hematologic Improvement [HI] or PR or CR) Per IWG Criteria | OR: HI/PR/CR per IWG. CR: BM:≤5% myeloblasts (all cell lines normal maturation), Peripheral blood:Hgb ≥11g/dL, PLTs ≥100x10^9/L, Neutrophils ≥1.0x10^9/L, Blasts 0%. PR: All CR criteria if abnormal before treatment except- BM blasts decreased ≥50% over pretreatment but still >5%, Cellularity, morphology not relevant. HI responses:1) Erythroid: Hgb increase ≥1.5 g/dL, Relevant reduction of red blood cell(RBC) units transfusions by absolute ≥4 RBC transfusions/8 week (wk) compared with pretreatment transfusion number in previous 8 wk. Only RBC transfusions given for Hgb of ≤9.0 g/dL.2)PLTs:Absolute increase ≥30x10^9/L starting >20x10^9/L PLTs; Increase from <20x10^9/L to >20x10^9/L and by ≥100%; 3)Neutrophil: ≥100% increase, absolute increase >0.5x10^9/L; 4)Progression/relapse after HI:≥1 of following:≥50% decrement from maximum response levels in granulocytes/PLTs, Reduction in Hgb ≥1.5 g/dL,Transfusion dependence. Data is reported separately for arm whose response was assessed per IWG. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Grade >= 3 TEAEs and Treatment Related Adverse Events | TEAEs defined as those events that 1) occur on or after the first dose of study drug, through the treatment phase, and for 30 days following the last dose of study drug or until subsequent anti-cancer therapy if earlier; 2) any event that is considered study drug-related regardless of the start date of the event; or 3) any event that is present at baseline but worsens in severity or is subsequently considered drug-related by the investigator. Grade >=3 TEAE defined as events that are severe, life-threatening or disabling, or fatal and considered related to imetelstat as per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. An AE was considered related to the study drug if the event was assessed by the investigator as probably or possibly related. |
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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 |
|---|---|---|---|---|---|---|
| Rochester | Minnesota | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26332545 | Derived | Tefferi A, Lasho TL, Begna KH, Patnaik MM, Zblewski DL, Finke CM, Laborde RR, Wassie E, Schimek L, Hanson CA, Gangat N, Wang X, Pardanani A. A Pilot Study of the Telomerase Inhibitor Imetelstat for Myelofibrosis. N Engl J Med. 2015 Sep 3;373(10):908-19. doi: 10.1056/NEJMoa1310523. |
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A total of 80 participants with Intermediate-2 or high-risk primary myelofibrosis (PMF)/post-polycythemia vera/essential thrombocythemia (post-PV/ET) MF (Arms A, B, C, E and F) or blast-phase MF (Arm D only) or spliceosome-mutated (or with ring sideroblasts) myelodysplastic syndromes [MDS]/ myeloproliferative neoplasm [MPN] (Arm G only) were enrolled to receive imetelstat. Arm C (Imetelstat 9.4 mg/kg [with MF]) was never initiated, participants allocated to Arm C were reassigned to Arm A or B.
Participants were enrolled at 1 site in the United States from 29 October 2012 to 22 January 2014 (end of recruitment). Data analyses includes data through 24 May 2018. Study has 4 phases: Screening Phase, Core Phase:up to nine 21-day (Arms A,B) or 28-day (Arms D,E,F,G) cycle, Extension Phase: after Cycle 9 to continue treatment with imetelstat; Event Monitoring Phase:Follow-up for those who discontinued treatment to collect survival status, disease status, and subsequent treatment information.
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm A: Imetelstat 9.4 mg/kg (MF) | Participants with MF regardless of spliceosome mutation status or presence of ring sideroblasts received imetelstat 9.4 milligram per kilogram (mg/kg), intravenously (IV) as 2-hour infusion on Day 1 of each 21-day cycle in Core Phase up to 9 cycles. Participants could receive imetelstat beyond Cycle 9 in the Extension Phase if they did not meet any of the withdrawal criteria, did not have disease progression and were receiving clinical benefit from treatment as determined by the investigator. Following treatment discontinuation, participants entered the Event Monitoring Phase for collection of survival status, disease status, and subsequent treatment information (Up to approximately 5.7 years). |
| FG001 | Arm B: Imetelstat 9.4 mg/kg as Induction + Maintenance (MF) | Participants with MF regardless of spliceosome mutation status or presence of ring sideroblasts received imetelstat 9.4 mg/kg, IV as 2-hour infusion on Days 1, 8, and 15 of 21-day cycle in Cycle 1 followed by 9.4 mg/kg on Day 1 of each 21-day cycle up to 9 cycles in the Core Phase. Participants could receive imetelstat beyond Cycle 9 in the Extension Phase if they did not meet any of the withdrawal criteria, did not have disease progression and were receiving clinical benefit from treatment as determined by the investigator. Following treatment discontinuation, participants entered the Event Monitoring Phase for collection of survival status, disease status, and subsequent treatment information (Up to approximately 5.7 years). |
| FG002 | Arm D: Imetelstat 9.4 mg/kg (Blast-phase MF/Acute Myeloid Leukemia) | Participants with blast-phase myelofibrosis/acute myeloid leukemia (MF/AML) received imetelstat 9.4 mg/kg, IV as 2-hour infusion weekly on Days 1, 8, 15, 22 of a 28-day cycle up to 9 cycles in the Core Phase. Participants could receive imetelstat beyond Cycle 9 in the Extension Phase if they did not meet any of the withdrawal criteria, did not have disease progression and were receiving clinical benefit from treatment as determined by the investigator. Following treatment discontinuation, participants entered the Event Monitoring Phase for collection of survival status, disease status, and subsequent treatment information (Up to approximately 5.7 years). |
| FG003 | Arm E: Imetelstat 7.5 - 9.4 mg/kg (MF [With Spliceosome Mutation or Ring Sideroblasts]) | Participants with MF and spliceosome mutations or ring sideroblasts present received 2 cycles (Cycles 1-2) of imetelstat 7.5 mg/kg, IV as 2-hour infusion on Day 1 of a 28-day cycle followed by maintenance therapy with the same regimen or the possibility of dose escalation to imetelstat 9.4 mg/kg weekly if response to the initial dose was insufficient up to 9 cycles in the Core Phase. Participants could receive imetelstat beyond Cycle 9 in the Extension Phase if they did not meet any of the withdrawal criteria, did not have disease progression and were receiving clinical benefit from treatment as determined by the investigator. Following treatment discontinuation, participants entered the Event Monitoring Phase for collection of survival status, disease status, and subsequent treatment information (Up to approximately 5.7 years). |
| FG004 | Arm F: Imetelstat 7.5 - 9.4 mg/kg (MF [Without Spliceosome Mutation and Ring Sideroblasts]) | Participants with MF without spliceosome mutations or ring sideroblasts present received 2 cycles (Cycles 1-2) of imetelstat 9.4 mg/kg, IV as 2-hour infusion on Day 1 of a 28-day cycle followed by maintenance therapy with the same regimen or imetelstat 7.5 mg/kg twice weekly on Days 1, 3 for 2 cycles of 28-day cycle (Cycles 3-4) followed by imetelstat 7.5 mg/kg 3-times-weekly on Days 1, 3, 5 of Cycles 5 and beyond of 28-day cycle up to 9 cycles in the Core Phase. Participants could receive imetelstat beyond Cycle 9 in the Extension Phase if they did not meet any of the withdrawal criteria, did not have disease progression and were receiving clinical benefit from treatment as determined by the investigator. Following treatment discontinuation, participants entered the Event Monitoring Phase for collection of survival status, disease status, and subsequent treatment information (Up to approximately 5.7 years). |
| FG005 | Arm G: Imetelstat 7.5 - 9.4 mg/kg (MDS/MPN or MDS With Spliceosome Mutations or Ring Sideroblasts) | Participants with either myelodysplastic syndromes/ myeloproliferative neoplasm (MDS/MPN) or MDS and spliceosome mutations or ring sideroblasts present received 2 cycles of 28-day cycle (Cycles 1-2) of imetelstat 7.5 mg/kg, IV as 2-hour infusion on Day 1 of a 28-day cycle followed by maintenance therapy with the same regimen or the possibility of dose escalation to imetelstat 9.4 mg/kg weekly if response to the initial dose was insufficient up to 9 cycles in the Core Phase. Participants could receive imetelstat beyond Cycle 9 in the Extension Phase if they did not meet any of the withdrawal criteria, did not have disease progression and were receiving clinical benefit from treatment as determined by the investigator. Following treatment discontinuation, participants entered the Event Monitoring Phase for collection of survival status, disease status, and subsequent treatment information (Up to approximately 5.7 years). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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All Treated Analysis Set included all participants who received at least one dose of imetelstat.
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm A: Imetelstat 9.4 mg/kg (MF) | Participants with MF regardless of spliceosome mutation status or presence of ring sideroblasts received imetelstat 9.4 mg/kg, IV as 2-hour infusion on Day 1 of each 21-day cycle in Core Phase up to 9 cycles. Participants could receive imetelstat beyond Cycle 9 in the Extension Phase if they did not meet any of the withdrawal criteria, did not have disease progression and were receiving clinical benefit from treatment as determined by the investigator. Following treatment discontinuation, participants entered the Event Monitoring Phase for collection of survival status, disease status, and subsequent treatment information (Up to approximately 5.7 years). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | MF Participants: Percentage of Participants With Overall Response (OR) - (Clinical Improvement[CI] or Partial Remission[PR] or Complete Remission[CR]) Per International Working Group - Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) Criteria | OR:CI/PR/CR per IWG-MRT. CR:Bone marrow (BM):<5% blasts;≤Grade 1 MF, AND Peripheral blood:Hemoglobin (Hb) ≥100 g/liter (g/L) and \ | Eligible Analysis Set included subset of all participants who received at least one dose of study drug that excludes ineligible participants who did not satisfy each and every eligibility criteria for study entry. Data is reported for arm groups (Arms A, B, E and F) whose overall response was assessed by IWG-MRT criteria. | Posted | Number | 95% Confidence Interval | percentage of participants |
From first dose of study drug to the last dose of study drug or until subsequent anti-cancer therapy if earlier (Up to approximately 5.7 years)
All treated analysis set included all participants who received at least 1 dose of Imetelstat. All non-serious adverse events (at 5% threshold) and serious adverse event including requirements for expedited reporting of serious adverse events occurring within 30 days of the last dose of study drug are reported.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm A: Imetelstat 9.4 mg/kg (MF) | Participants with MF regardless of spliceosome mutation status or presence of ring sideroblasts received imetelstat 9.4 mg/kg, IV as 2-hour infusion on Day 1 of each 21-day cycle in Core Phase up to 9 cycles. Participants could receive imetelstat beyond Cycle 9 in the Extension Phase if they did not meet any of the withdrawal criteria, did not have disease progression and were receiving clinical benefit from treatment as determined by the investigator. Following treatment discontinuation, participants entered the Event Monitoring Phase for collection of survival status, disease status, and subsequent treatment information (Up to approximately 5.7 years). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Platelet count decreased | Investigations | MedDRA (12.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (12.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Geron Corp. | 650-473-7700 | myf2001-info@geron.com |
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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 | Oct 5, 2015 | May 14, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 16, 2018 | May 14, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D055728 | Primary Myelofibrosis |
| D009190 | Myelodysplastic Syndromes |
| D009196 | Myeloproliferative Disorders |
| ID | Term |
|---|---|
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| C519562 | imetelstat |
| C505952 | GRN163L peptide |
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|
| Arm E: Imetelstat 7.5 - 9.4 mg/kg (MF [with Spliceosome Mutation or Ring Sideroblasts]) | Experimental | Participants with MF and spliceosome mutations or ring sideroblasts present received 2 cycles (Cycles 1-2) of imetelstat 7.5 mg/kg, IV as 2-hour infusion on Day 1 of a 28-day cycle followed by maintenance therapy with the same regimen or the possibility of dose escalation to imetelstat 9.4 mg/kg weekly if response to the initial dose was insufficient up to 9 cycles in the Core Phase. Participants could receive imetelstat beyond Cycle 9 in the Extension Phase if they did not meet any of the withdrawal criteria, did not have disease progression and were receiving clinical benefit from treatment as determined by the investigator. Following treatment discontinuation, participants entered the Event Monitoring Phase for collection of survival status, disease status, and subsequent treatment information (Up to approximately 5.7 years). |
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| Arm F: Imetelstat 7.5 - 9.4 mg/kg (MF [without spliceosome mutation and ring sideroblasts]) | Experimental | Participants with MF without spliceosome mutations or ring sideroblasts present received 2 cycles (Cycles 1-2) of imetelstat 9.4 mg/kg, IV as 2-hour infusion on Day 1 of a 28-day cycle followed by maintenance therapy with the same regimen or imetelstat 7.5 mg/kg twice weekly on Days 1, 3 for 2 cycles of 28-day cycle (Cycles 3-4) followed by imetelstat 7.5 mg/kg 3-times-weekly on Days 1, 3, 5 of Cycles 5 and beyond of 28-day cycle up to 9 cycles in the Core Phase. Participants could receive imetelstat beyond Cycle 9 in the Extension Phase if they did not meet any of the withdrawal criteria, did not have disease progression and were receiving clinical benefit from treatment as determined by the investigator. Following treatment discontinuation, participants entered the Event Monitoring Phase for collection of survival status, disease status, and subsequent treatment information (Up to approximately 5.7 years). |
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| Arm G: Imetelstat 7.5 - 9.4 mg/kg (MDS/MPN or MDS with Spliceosome Mutations or Ring Sideroblasts) | Experimental | Participants with either myelodysplastic syndromes/ myeloproliferative neoplasm (MDS/MPN) or MDS and spliceosome mutations or ring sideroblasts present received 2 cycles of 28-day cycle (Cycles 1-2) of imetelstat 7.5 mg/kg, IV as 2-hour infusion on Day 1 of a 28-day cycle followed by maintenance therapy with the same regimen or the possibility of dose escalation to imetelstat 9.4 mg/kg weekly if response to the initial dose was insufficient up to 9 cycles in the Core Phase. Participants could receive imetelstat beyond Cycle 9 in the Extension Phase if they did not meet any of the withdrawal criteria, did not have disease progression and were receiving clinical benefit from treatment as determined by the investigator. Following treatment discontinuation, participants entered the Event Monitoring Phase for collection of survival status, disease status, and subsequent treatment information (Up to approximately 5.7 years). |
|
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| Up to first 9 cycles of treatment (each cycle was of 28 days for Arm G) |
| From first dose of study drug up to 30 days from the last dose of study drug or until subsequent anti-cancer therapy if earlier (Up to approximately 5.7 years) |
| Number of Participants With Spleen Response Per IWG-MRT Criteria | Spleen response per IWG-MRT criteria defined as baseline splenomegaly that is palpable at 5-10 cm, below the LCM, becomes not palpable, OR A baseline splenomegaly that is palpable at >10 cm, below the LCM, decreases by ≥50%. Baseline splenomegaly that is palpable at <5 cm, below the LCM, is not eligible for spleen response. Confirmation by Magnetic resonance imaging (MRI) or computerized tomography (CT) showing ≥35% spleen volume reduction is recommended (but not required). Spleen response was assessed only in participants with MF. | Up to approximately 5.7 years |
| MF and Blastic MF/AML Participants: Number of Participants With Transfusion Independence (CI by Anemia Response) Per IWG-MRT | Transfusion dependency was defined by a history of at least 2 units of red blood cell transfusions in the last month for a hemoglobin level of less than 85 g/L that was not associated with clinically overt bleeding. A participant who was transfusion dependent at baseline was considered transfusion independent if the participant met either of the following conditions: Received no more than 1 unit of red blood cell transfusions in a rolling time interval of 30 days or more, and had a hemoglobin level increase over baseline more than 2 g/dL if participant baseline hemoglobin level was less than 85 g/L and received no transfusion. Anemia response per IWG-MRT Criteria- Transfusion-independent participants: a ≥20 g/L increase in hemoglobin level. Transfusion-dependent participants: becoming transfusion-independent. Data is reported separately for arms assessed as per the IWG-MRT criteria. | Up to approximately 5.7 years |
| MDS Participants: Number of Participants With Transfusion Independence (HI by Erythroid Response) Per IWG Criteria | Transfusion dependency was defined by a history of at least 2 units of red blood cell transfusions in the last month for a hemoglobin level of less than 85 g/L that was not associated with clinically overt bleeding. A participant who was transfusion dependent at baseline was considered transfusion independent if the participant met either of the following conditions: Received no more than 1 unit of red blood cell transfusions in a rolling time interval of 30 days or more, and had a hemoglobin level increase over baseline more than 2 g/dL if participant baseline hemoglobin level was less than 85 g/L and received no transfusion. HI responses included: 1) Erythroid: Hgb increase ≥1.5 g/dL, Relevant reduction of RBC units transfusions by absolute number of >=4 RBC transfusions/8 week compared with pretreatment transfusion number in previous 8 week. Only RBC transfusions given for Hgb of ≤9.0 g/dL. Data is reported separately for arm assessed as per IWG criteria. | Up to approximately 5.7 years |
| MF Participants: Time to Response | Time to response was defined as the duration from study Day 1 to the earliest date that a response is first documented. The response CI/CR/PR was assessed by IWG-MRT criteria. | From study Day 1 to the earliest date that a response was first documented (Up to approximately 5.7 years) |
| Blastic MF/AML Participants: Time to Response | Time to response was defined as the duration from study Day 1 to the earliest date that a response is first documented. Response was defined as achievement of a leukemic response (i.e. a clinically meaningful reduction in Blast cells). This was quantified as <5% peripheral blood and bone marrow blasts % that lasts for at least two months. Data for time to response is reported as per criteria of response assessment. | From study Day 1 to the earliest date that a response was first documented (Up to approximately 5.7 years) |
| MDS Participants: Time to Response | Time to response was defined as the duration from study Day 1 to the earliest date that a response is first documented. Response was defined as HI, PR or CR per IWG criteria. Data for time to response is reported as per criteria of response assessment. | From study Day 1 to the earliest date that a response was first documented (Up to approximately 5.7 years) |
| MF Participants: Duration of Response (DOR) Per IWG-MRT Criteria | DOR measured from time of initial response (CR/PR/CI) until documented PD or death whichever occurs first. If no PD/death occurs DOR is censored at last disease evaluation date for responders. CR:BM: <5%blasts; ≤Grade 1 MF, AND Peripheral blood:Hb≥100 g/L and <UNL;Neutrophil count≥1x10^9/L and <UNL;PLT count≥100x10^9/L and <UNL;<2% IMCs, AND Clinical:Resolution of disease symptoms;Spleen and liver not palpable;No evidence of EMH.PR:All CR criteria plus peripheral blood:Hb≥85 but <100g/L and <UNL;NC≥1x10^9/L and <UNL;PLTcount ≥50 but<100x10^9/L and<UNL;<2%IMCs. CI:achievement of anemia(≥20 g/L increase Hb level),spleen(baseline splenomegaly-palpable at 5-10cm,below LCM,becomes not palpable) or symptoms response(50% reduction in total symptom score) without PD(appearance of new splenomegaly- palpable[>= 5 cm below LCM) or increase in severity of anemia, thrombocytopenia or neutropenia. Data is reported separately for arms whose DOR was assessed per IWG-MRT. Kaplan-Meier method was used.](streamdown:incomplete-link) | From time of initial response until documented disease progression or death whichever occurs first (Up to approximately 5.7 years) |
| Blastic MF/AML Participants: Duration of Response | DOR was measured from the time of initial response until documented disease progression or death whichever occurs first. If no PD/death occurs the DOR is censored at last disease evaluation date for responders. Response is defined as achievement of <5% peripheral blood and bone marrow blast % that lasts for at least two months. PD is the appearance of new splenomegaly that is palpable at least 5 cm below the LCM. Data is reported separately for arm whose DOR was assessed by a specific criterion. Kaplan-Meier method was used. | From time of initial response until documented disease progression or death whichever occurs first (Up to approximately 5.7 years) |
| MDS Participants: Duration of Response Per IWG Criteria | DOR: time of initial response (CR/PR/HI) until documented PD/death whichever occurs first. If no PD/death occurs DOR is censored at last disease evaluation date for responders. Data reported separately for arm assessed per IWG. Kaplan-Meier method was used. | From the time of initial response (CR/PR/HI) until documented disease progression or death whichever occurs first (Up to approximately 5.7 years) |
| Overall Survival (OS) | OS was defined as the as the interval from Study Day 1 to the date of death from any cause. Survival time of living participants was censored on the last date a participant is known to be alive or lost to follow-up. Overall Survival was estimated by Kaplan-Meier method. | From Study Day 1 to the date of death from any cause (Up to approximately 5.7 years) |
| Lost to Follow-up |
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| Withdrawal of Consent |
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| Death |
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| BG001 | Arm B: Imetelstat 9.4 mg/kg as Induction + Maintenance (MF) | Participants with MF regardless of spliceosome mutation status or presence of ring sideroblasts received imetelstat 9.4 mg/kg, IV as 2-hour infusion on Days 1, 8, and 15 of 21-day cycle in Cycle 1 followed by 9.4 mg/kg on Day 1 of each 21-day cycle up to 9 cycles in the Core Phase. Participants could receive imetelstat beyond Cycle 9 in the Extension Phase if they did not meet any of the withdrawal criteria, did not have disease progression and were receiving clinical benefit from treatment as determined by the investigator. Following treatment discontinuation, participants entered the Event Monitoring Phase for collection of survival status, disease status, and subsequent treatment information (Up to approximately 5.7 years). |
| BG002 | Arm D: Imetelstat 9.4 mg/kg (Blast-phase MF/Acute Myeloid Leukemia) | Participants with blast-phase MF/AML received imetelstat 9.4 mg/kg, IV as 2-hour infusion weekly on Days 1, 8, 15, 22 of a 28-day cycle up to 9 cycles in the Core Phase. Participants could receive imetelstat beyond Cycle 9 in the Extension Phase if they did not meet any of the withdrawal criteria, did not have disease progression and were receiving clinical benefit from treatment as determined by the investigator. Following treatment discontinuation, participants entered the Event Monitoring Phase for collection of survival status, disease status, and subsequent treatment information (Up to approximately 5.7 years). |
| BG003 | Arm E: Imetelstat 7.5 - 9.4 mg/kg (MF [With Spliceosome Mutation or Ring Sideroblasts]) | Participants with MF and spliceosome mutations or ring sideroblasts present received 2 cycles (Cycles 1-2) of imetelstat 7.5 mg/kg, IV as 2-hour infusion on Day 1 of a 28-day cycle followed by maintenance therapy with the same regimen or the possibility of dose escalation to imetelstat 9.4 mg/kg weekly if response to the initial dose was insufficient up to 9 cycles in the Core Phase. Participants could receive imetelstat beyond Cycle 9 in the Extension Phase if they did not meet any of the withdrawal criteria, did not have disease progression and were receiving clinical benefit from treatment as determined by the investigator. Following treatment discontinuation, participants entered the Event Monitoring Phase for collection of survival status, disease status, and subsequent treatment information (Up to approximately 5.7 years). |
| BG004 | Arm F: Imetelstat 7.5 - 9.4 mg/kg (MF [Without Spliceosome Mutation and Ring Sideroblasts]) | Participants with MF without spliceosome mutations or ring sideroblasts present received 2 cycles (Cycles 1-2) of imetelstat 9.4 mg/kg, IV as 2-hour infusion on Day 1 of a 28-day cycle followed by maintenance therapy with the same regimen or imetelstat 7.5 mg/kg twice weekly on Days 1, 3 for 2 cycles of 28-day cycle (Cycles 3-4) followed by imetelstat 7.5 mg/kg 3-times-weekly on Days 1, 3, 5 of Cycles 5 and beyond of 28-day cycle up to 9 cycles in the Core Phase. Participants could receive imetelstat beyond Cycle 9 in the Extension Phase if they did not meet any of the withdrawal criteria, did not have disease progression and were receiving clinical benefit from treatment as determined by the investigator. Following treatment discontinuation, participants entered the Event Monitoring Phase for collection of survival status, disease status, and subsequent treatment information (Up to approximately 5.7 years). |
| BG005 | Arm G: Imetelstat 7.5 - 9.4 mg/kg (MDS/MPN or MDS With Spliceosome Mutations or Ring Sideroblasts) | Participants with either MDS/MPN or MDS and spliceosome mutations or ring sideroblasts present received 2 cycles of 28-day cycle (Cycles 1-2) of imetelstat 7.5 mg/kg, IV as 2-hour infusion on Day 1 of a 28-day cycle followed by maintenance therapy with the same regimen or the possibility of dose escalation to imetelstat 9.4 mg/kg weekly if response to the initial dose was insufficient up to 9 cycles in the Core Phase. Participants could receive imetelstat beyond Cycle 9 in the Extension Phase if they did not meet any of the withdrawal criteria, did not have disease progression and were receiving clinical benefit from treatment as determined by the investigator. Following treatment discontinuation, participants entered the Event Monitoring Phase for collection of survival status, disease status, and subsequent treatment information (Up to approximately 5.7 years). |
| BG006 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Eastern Cooperative Oncology Group (ECOG) Performance Status Score | ECOG Performance Status has 5 Scores.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/sedentary nature,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/chair more than 50% of waking hours;4= Completely disabled. Cannot carry on any self-care.Totally confined to bed/chair;5= Dead. Number of participants for each score are reported. | Count of Participants | Participants |
|
| Myelofibrosis subtype | Myelofibrosis subtypes included MDS/MPN or MDS, blast-phase myelofibrosis, primary myelofibrosis, post-ET myelofibrosis, and Post-PV myelofibrosis. Number of participants for each subtype are reported. | Count of Participants | Participants |
|
| Dynamic International Prognostic Scoring System (DIPSS)-Plus Risk Status | 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 <10 grams per deciliter (gm/dL), Leukocytes >10 (9)/L, circulating blasts ≥1%, and constitutional symptoms. Participants for each status are reported. Only categories with data are reported. | Number analyzed is the number of participants with data available for DIPSS-Plus risk status. | Count of Participants | Participants |
|
| Spliceosomal Mutation Status | Spliceosome mutations represent a group of acquired genetic alterations that affect both myeloid and lymphoid malignancies. | Number analyzed is the number of participants with data available for spliceosomal mutation status. | Count of Participants | Participants |
|
| Spliceosomal Mutation Type | Spliceosome mutations represent a group of acquired genetic alterations that affect both myeloid and lymphoid malignancies. Spliceosomal mutation type included SF3B1, SRSF2 and U2AF1. Number of participants for each type are reported. | Number analyzed is the number of participants with data available for spliceosomal mutation type. | Count of Participants | Participants |
|
| Ringed Sideroblasts Present | Ring sideroblasts are erythroblasts with iron-loaded mitochondria visualized by Prussian blue staining (Perls' reaction) as a perinuclear ring of blue granules. Refractory anemia with ring sideroblasts (RARS) is a type of MDS that is characterized by anemia and the presence of at least 15 percent ring sideroblasts in the marrow. | Number analyzed is the number of participants with data available for ringed sideroblasts present. | Count of Participants | Participants |
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| JAK2V617F Mutation | JAK2 V617F mutation is an acquired, somatic mutation present in the majority of participants with myeloproliferative cancer (myeloproliferative neoplasms) i.e. nearly 100% of participants with polycythemia vera and in about 50% of participants with essential thrombocytosis and primary myelofibrosis. | Number analyzed is the number of participants with data available for JAK2V617F Mutation. | Count of Participants | Participants |
|
| Transfusion Dependent | Transfusion dependency was defined by a history of at least 2 units of red blood cell transfusions in the last month for a hemoglobin level of less than 85 grams per deciliter (g/dL) that was not associated with clinically overt bleeding. | Count of Participants | Participants |
|
| Up to first 9 cycles of treatment (each cycle was of 21 days for Arms A and B and 28 days for Arms E and F) |
|
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| Primary | Blastic MF/AML Participants: Percentage of Participants With Overall Response | For this pilot study, overall response was defined as achievement of a leukemic response (i.e. a clinically meaningful reduction in Blast cells). This was quantified as <5% peripheral blood and bone marrow blasts % that lasts for at least two months. Data is reported separately for this arm where response was assessed by this specific criterion. | All Treated Analysis Set included all participants who received at least one dose of study drug. Data is reported for Arm D: Imetelstat 9.4 mg/kg (Blastic MF/AML) participants whose overall response was assessed by a specific criterion. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to first 9 cycles of treatment (each cycle was of 28 days for Arm D) |
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| Primary | MDS Participants: Percentage of Participants With Overall Response (Hematologic Improvement [HI] or PR or CR) Per IWG Criteria | OR: HI/PR/CR per IWG. CR: BM:≤5% myeloblasts (all cell lines normal maturation), Peripheral blood:Hgb ≥11g/dL, PLTs ≥100x10^9/L, Neutrophils ≥1.0x10^9/L, Blasts 0%. PR: All CR criteria if abnormal before treatment except- BM blasts decreased ≥50% over pretreatment but still >5%, Cellularity, morphology not relevant. HI responses:1) Erythroid: Hgb increase ≥1.5 g/dL, Relevant reduction of red blood cell(RBC) units transfusions by absolute ≥4 RBC transfusions/8 week (wk) compared with pretreatment transfusion number in previous 8 wk. Only RBC transfusions given for Hgb of ≤9.0 g/dL.2)PLTs:Absolute increase ≥30x10^9/L starting >20x10^9/L PLTs; Increase from <20x10^9/L to >20x10^9/L and by ≥100%; 3)Neutrophil: ≥100% increase, absolute increase >0.5x10^9/L; 4)Progression/relapse after HI:≥1 of following:≥50% decrement from maximum response levels in granulocytes/PLTs, Reduction in Hgb ≥1.5 g/dL,Transfusion dependence. Data is reported separately for arm whose response was assessed per IWG. | All Treated Analysis Set included all participants who received at least one dose of the study drug. Data is reported for Arm G: Imetelstat 9.4 mg/kg (MDS/MPN or MDS and spliceosome mutations or ring sideroblasts) participants whose overall response was assessed by IWG criteria. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to first 9 cycles of treatment (each cycle was of 28 days for Arm G) |
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| Secondary | Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Grade >= 3 TEAEs and Treatment Related Adverse Events | TEAEs defined as those events that 1) occur on or after the first dose of study drug, through the treatment phase, and for 30 days following the last dose of study drug or until subsequent anti-cancer therapy if earlier; 2) any event that is considered study drug-related regardless of the start date of the event; or 3) any event that is present at baseline but worsens in severity or is subsequently considered drug-related by the investigator. Grade >=3 TEAE defined as events that are severe, life-threatening or disabling, or fatal and considered related to imetelstat as per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. An AE was considered related to the study drug if the event was assessed by the investigator as probably or possibly related. | All Treated Analysis Set included all participants who received at least one dose of imetelstat. | Posted | Number | percentage of participants | From first dose of study drug up to 30 days from the last dose of study drug or until subsequent anti-cancer therapy if earlier (Up to approximately 5.7 years) |
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| Secondary | Number of Participants With Spleen Response Per IWG-MRT Criteria | Spleen response per IWG-MRT criteria defined as baseline splenomegaly that is palpable at 5-10 cm, below the LCM, becomes not palpable, OR A baseline splenomegaly that is palpable at >10 cm, below the LCM, decreases by ≥50%. Baseline splenomegaly that is palpable at <5 cm, below the LCM, is not eligible for spleen response. Confirmation by Magnetic resonance imaging (MRI) or computerized tomography (CT) showing ≥35% spleen volume reduction is recommended (but not required). Spleen response was assessed only in participants with MF. | Arms A, B, E and F: Eligible Analysis Set included subset of all participants who received at least one dose of study drug that excludes ineligible participants who did not satisfy each and every eligibility criteria for study entry. Arm D: All Treated Analysis Set included all participants who received at least one dose of imetelstat. | Posted | Count of Participants | Participants | Up to approximately 5.7 years |
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|
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| Secondary | MF and Blastic MF/AML Participants: Number of Participants With Transfusion Independence (CI by Anemia Response) Per IWG-MRT | Transfusion dependency was defined by a history of at least 2 units of red blood cell transfusions in the last month for a hemoglobin level of less than 85 g/L that was not associated with clinically overt bleeding. A participant who was transfusion dependent at baseline was considered transfusion independent if the participant met either of the following conditions: Received no more than 1 unit of red blood cell transfusions in a rolling time interval of 30 days or more, and had a hemoglobin level increase over baseline more than 2 g/dL if participant baseline hemoglobin level was less than 85 g/L and received no transfusion. Anemia response per IWG-MRT Criteria- Transfusion-independent participants: a ≥20 g/L increase in hemoglobin level. Transfusion-dependent participants: becoming transfusion-independent. Data is reported separately for arms assessed as per the IWG-MRT criteria. | Arms A, B, E, F: Eligible Analysis Set included subset of all participants who received at least one dose of study drug that excludes ineligible participants who did not satisfy each and every eligibility criteria for study entry. Arm D: All Treated Analysis Set included all participants who received at least one dose of imetelstat, assessed per IWG-MRT. | Posted | Count of Participants | Participants | Up to approximately 5.7 years |
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| Secondary | MDS Participants: Number of Participants With Transfusion Independence (HI by Erythroid Response) Per IWG Criteria | Transfusion dependency was defined by a history of at least 2 units of red blood cell transfusions in the last month for a hemoglobin level of less than 85 g/L that was not associated with clinically overt bleeding. A participant who was transfusion dependent at baseline was considered transfusion independent if the participant met either of the following conditions: Received no more than 1 unit of red blood cell transfusions in a rolling time interval of 30 days or more, and had a hemoglobin level increase over baseline more than 2 g/dL if participant baseline hemoglobin level was less than 85 g/L and received no transfusion. HI responses included: 1) Erythroid: Hgb increase ≥1.5 g/dL, Relevant reduction of RBC units transfusions by absolute number of >=4 RBC transfusions/8 week compared with pretreatment transfusion number in previous 8 week. Only RBC transfusions given for Hgb of ≤9.0 g/dL. Data is reported separately for arm assessed as per IWG criteria. | All Treated Analysis Set included all participants who received at least one dose of study drug. Data is reported for Arm G: Imetelstat 9.4 mg/kg (MDS/MPN or MDS and spliceosome mutations or ring sideroblasts) participants whose transfusion independence (HI by erythroid response) was assessed by IWG criteria. | Posted | Count of Participants | Participants | Up to approximately 5.7 years |
|
|
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| Secondary | MF Participants: Time to Response | Time to response was defined as the duration from study Day 1 to the earliest date that a response is first documented. The response CI/CR/PR was assessed by IWG-MRT criteria. | Eligible Analysis Set included subset of all participants who received at least one dose of study drug that excludes ineligible participants who did not satisfy each and every eligibility criteria for study entry. Data is reported for arm groups (Arms A, B, E and F) whose overall response was assessed by IWG-MRT criteria. Only responders were analyzed for this outcome measure. | Posted | Median | Full Range | months | From study Day 1 to the earliest date that a response was first documented (Up to approximately 5.7 years) |
|
|
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| Secondary | Blastic MF/AML Participants: Time to Response | Time to response was defined as the duration from study Day 1 to the earliest date that a response is first documented. Response was defined as achievement of a leukemic response (i.e. a clinically meaningful reduction in Blast cells). This was quantified as <5% peripheral blood and bone marrow blasts % that lasts for at least two months. Data for time to response is reported as per criteria of response assessment. | All Treated Analysis Set included all participants who received at least one dose of the study drug. Only responders were analyzed for this outcome measure. Data is reported for Arm D: Imetelstat 9.4 mg/kg (Blastic MF/AML) participants whose overall response was assessed by a specific criterion. | Posted | From study Day 1 to the earliest date that a response was first documented (Up to approximately 5.7 years) |
|
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| Secondary | MDS Participants: Time to Response | Time to response was defined as the duration from study Day 1 to the earliest date that a response is first documented. Response was defined as HI, PR or CR per IWG criteria. Data for time to response is reported as per criteria of response assessment. | All Treated Analysis Set included all participants who received at least one dose of the study drug. Only responders were analyzed for this outcome measure. Data is reported for Arm G: Imetelstat 9.4 mg/kg (MDS/MPN or MDS and spliceosome mutations or ring sideroblasts) participants whose overall response was assessed by IWG criteria. | Posted | Median | Full Range | months | From study Day 1 to the earliest date that a response was first documented (Up to approximately 5.7 years) |
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| Secondary | MF Participants: Duration of Response (DOR) Per IWG-MRT Criteria | DOR measured from time of initial response (CR/PR/CI) until documented PD or death whichever occurs first. If no PD/death occurs DOR is censored at last disease evaluation date for responders. CR:BM: <5%blasts; ≤Grade 1 MF, AND Peripheral blood:Hb≥100 g/L and <UNL;Neutrophil count≥1x10^9/L and <UNL;PLT count≥100x10^9/L and <UNL;<2% IMCs, AND Clinical:Resolution of disease symptoms;Spleen and liver not palpable;No evidence of EMH.PR:All CR criteria plus peripheral blood:Hb≥85 but <100g/L and <UNL;NC≥1x10^9/L and <UNL;PLTcount ≥50 but<100x10^9/L and<UNL;<2%IMCs. CI:achievement of anemia(≥20 g/L increase Hb level),spleen(baseline splenomegaly-palpable at 5-10cm,below LCM,becomes not palpable) or symptoms response(50% reduction in total symptom score) without PD(appearance of new splenomegaly- palpable[>= 5 cm below LCM) or increase in severity of anemia, thrombocytopenia or neutropenia. Data is reported separately for arms whose DOR was assessed per IWG-MRT. Kaplan-Meier method was used.](streamdown:incomplete-link) | Eligible Analysis Set included subset of all participants who received at least one dose of study drug that excludes ineligible participants who did not satisfy each and every eligibility criteria for study entry. Data is reported for arm groups whose DOR was assessed by IWG-MRT criteria. Only responders were analyzed for this outcome measure. | Posted | Median | 95% Confidence Interval | months | From time of initial response until documented disease progression or death whichever occurs first (Up to approximately 5.7 years) |
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| Secondary | Blastic MF/AML Participants: Duration of Response | DOR was measured from the time of initial response until documented disease progression or death whichever occurs first. If no PD/death occurs the DOR is censored at last disease evaluation date for responders. Response is defined as achievement of <5% peripheral blood and bone marrow blast % that lasts for at least two months. PD is the appearance of new splenomegaly that is palpable at least 5 cm below the LCM. Data is reported separately for arm whose DOR was assessed by a specific criterion. Kaplan-Meier method was used. | All Treated Analysis Set included all participants who received at least one dose of the study drug. Data is reported for Arm D: Imetelstat 9.4 mg/kg (Blastic MF/AML) participants whose DOR was assessed by a specific criterion. Only responders were analyzed for this outcome measure. | Posted | From time of initial response until documented disease progression or death whichever occurs first (Up to approximately 5.7 years) |
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| Secondary | MDS Participants: Duration of Response Per IWG Criteria | DOR: time of initial response (CR/PR/HI) until documented PD/death whichever occurs first. If no PD/death occurs DOR is censored at last disease evaluation date for responders. Data reported separately for arm assessed per IWG. Kaplan-Meier method was used. | All Treated Analysis Set included all participants who received at least one dose of the study drug. Data is reported for Arm G: Imetelstat 9.4 mg/kg (MDS/MPN or MDS and spliceosome mutations or ring sideroblasts) participants whose DOR was assessed by IWG criteria. Only responders were analyzed for this outcome measure. | Posted | Median | 95% Confidence Interval | months | From the time of initial response (CR/PR/HI) until documented disease progression or death whichever occurs first (Up to approximately 5.7 years) |
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| Secondary | Overall Survival (OS) | OS was defined as the as the interval from Study Day 1 to the date of death from any cause. Survival time of living participants was censored on the last date a participant is known to be alive or lost to follow-up. Overall Survival was estimated by Kaplan-Meier method. | All Treated Analysis Set included all participants who received at least one dose of imetelstat. | Posted | Median | 95% Confidence Interval | months | From Study Day 1 to the date of death from any cause (Up to approximately 5.7 years) |
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| 13 |
| 19 |
| 17 |
| 19 |
| 19 |
| 19 |
| EG001 | Arm B: Imetelstat 9.4 mg/kg as Induction + Maintenance (MF) | Participants with MF regardless of spliceosome mutation status or presence of ring sideroblasts received imetelstat 9.4 mg/kg, IV as 2-hour infusion on Days 1, 8, and 15 of 21-day cycle in Cycle 1 followed by 9.4 mg/kg on Day 1 of each 21-day cycle up to 9 cycles in the Core Phase. Participants could receive imetelstat beyond Cycle 9 in the Extension Phase if they did not meet any of the withdrawal criteria, did not have disease progression and were receiving clinical benefit from treatment as determined by the investigator. Following treatment discontinuation, participants entered the Event Monitoring Phase for collection of survival status, disease status, and subsequent treatment information (Up to approximately 5.7 years). | 15 | 16 | 12 | 16 | 16 | 16 |
| EG002 | Arm D: Imetelstat 9.4 mg/kg (Blast-phase MF/Acute Myeloid Leukemia | Participants with blast-phase MF/AML received imetelstat 9.4 mg/kg, IV as 2-hour infusion weekly on Days 1, 8, 15, 22 of a 28-day cycle up to 9 cycles in the Core Phase. Participants could receive imetelstat beyond Cycle 9 in the Extension Phase if they did not meet any of the withdrawal criteria, did not have disease progression and were receiving clinical benefit from treatment as determined by the investigator. Following treatment discontinuation, participants entered the Event Monitoring Phase for collection of survival status, disease status, and subsequent treatment information (Up to approximately 5.7 years). | 9 | 9 | 9 | 9 | 9 | 9 |
| EG003 | Arm E: Imetelstat 7.5 - 9.4 mg/kg (MF [With Spliceosome Mutation or Ring Sideroblasts]) | Participants with MF and spliceosome mutations or ring sideroblasts present received 2 cycles (Cycles 1-2) of imetelstat 7.5 mg/kg, IV as 2-hour infusion on Day 1 of a 28-day cycle followed by maintenance therapy with the same regimen or the possibility of dose escalation to imetelstat 9.4 mg/kg weekly if response to the initial dose was insufficient up to 9 cycles in the Core Phase. Participants could receive imetelstat beyond Cycle 9 in the Extension Phase if they did not meet any of the withdrawal criteria, did not have disease progression and were receiving clinical benefit from treatment as determined by the investigator. Following treatment discontinuation, participants entered the Event Monitoring Phase for collection of survival status, disease status, and subsequent treatment information (Up to approximately 5.7 years). | 8 | 9 | 7 | 9 | 9 | 9 |
| EG004 | Arm F: Imetelstat 7.5 - 9.4 mg/kg (MF [Without Spliceosome Mutation and Ring Sideroblasts]) | Participants with MF without spliceosome mutations or ring sideroblasts present received 2 cycles (Cycles 1-2) of imetelstat 9.4 mg/kg, IV as 2-hour infusion on Day 1 of a 28-day cycle followed by maintenance therapy with the same regimen or imetelstat 7.5 mg/kg twice weekly on Days 1, 3 for 2 cycles of 28-day cycle (Cycles 3-4) followed by imetelstat 7.5 mg/kg 3-times-weekly on Days 1, 3, 5 of Cycles 5 and beyond of 28-day cycle up to 9 cycles in the Core Phase. Participants could receive imetelstat beyond Cycle 9 in the Extension Phase if they did not meet any of the withdrawal criteria, did not have disease progression and were receiving clinical benefit from treatment as determined by the investigator. Following treatment discontinuation, participants entered the Event Monitoring Phase for collection of survival status, disease status, and subsequent treatment information (Up to approximately 5.7 years). | 9 | 18 | 14 | 18 | 18 | 18 |
| EG005 | Arm G: Imetelstat 7.5 - 9.4 mg/kg (MDS/MPN or MDS With Spliceosome Mutations or Ring Sideroblasts) | Participants with either MDS/MPN or MDS and spliceosome mutations or ring sideroblasts present received 2 cycles of 28-day cycle (Cycles 1-2) of imetelstat 7.5 mg/kg, IV as 2-hour infusion on Day 1 of a 28-day cycle followed by maintenance therapy with the same regimen or the possibility of dose escalation to imetelstat 9.4 mg/kg weekly if response to the initial dose was insufficient up to 9 cycles in the Core Phase. Participants could receive imetelstat beyond Cycle 9 in the Extension Phase if they did not meet any of the withdrawal criteria, did not have disease progression and were receiving clinical benefit from treatment as determined by the investigator. Following treatment discontinuation, participants entered the Event Monitoring Phase for collection of survival status, disease status, and subsequent treatment information (Up to approximately 5.7 years). | 6 | 9 | 9 | 9 | 9 | 9 |
| Neutrophil count decreased | Investigations | MedDRA (12.0) | Systematic Assessment |
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| White blood cell count decreased | Investigations | MedDRA (12.0) | Systematic Assessment |
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| Anaemia | Blood and lymphatic system disorders | MedDRA (12.0) | Systematic Assessment |
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| Lung infection | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
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| Sepsis | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
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| Atrial fibrillation | Cardiac disorders | MedDRA (12.0) | Systematic Assessment |
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| Cardiac failure | Cardiac disorders | MedDRA (12.0) | Systematic Assessment |
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| Fatigue | General disorders | MedDRA (12.0) | Systematic Assessment |
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| Atrial fibrillation | Cardiac disorders | MedDRA (12.0) | Systematic Assessment |
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| Cardiac failure | Cardiac disorders | MedDRA (12.0) | Systematic Assessment |
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| Sinus tachycardia | Cardiac disorders | MedDRA (12.0) | Systematic Assessment |
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| Eye disorders | Eye disorders | MedDRA (12.0) | Systematic Assessment |
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| Abdominal distension | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
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| Chills | General disorders | MedDRA (12.0) | Systematic Assessment |
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| Early satiety | General disorders | MedDRA (12.0) | Systematic Assessment |
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| Fatigue | General disorders | MedDRA (12.0) | Systematic Assessment |
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| Infusion related reaction | General disorders | MedDRA (12.0) | Systematic Assessment |
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| Non-cardiac chest pain | General disorders | MedDRA (12.0) | Systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA (12.0) | Systematic Assessment |
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| Pain | General disorders | MedDRA (12.0) | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA (12.0) | Systematic Assessment |
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| Lung infection | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
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| Sinusitis | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA (12.0) | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA (12.0) | Systematic Assessment |
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| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA (12.0) | Systematic Assessment |
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| Activated partial thromboplastin time prolonged | Investigations | MedDRA (12.0) | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA (12.0) | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA (12.0) | Systematic Assessment |
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| Blood alkaline phosphatase increased | Investigations | MedDRA (12.0) | Systematic Assessment |
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| Blood amylase increased | Investigations | MedDRA (12.0) | Systematic Assessment |
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| Blood bilirubin increased | Investigations | MedDRA (12.0) | Systematic Assessment |
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| Blood creatinine increased | Investigations | MedDRA (12.0) | Systematic Assessment |
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| Gamma-glutamyltransferase increased | Investigations | MedDRA (12.0) | Systematic Assessment |
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| Lipase increased | Investigations | MedDRA (12.0) | Systematic Assessment |
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| Lymphocyte count decreased | Investigations | MedDRA (12.0) | Systematic Assessment |
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| Neutrophil count decreased | Investigations | MedDRA (12.0) | Systematic Assessment |
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| Platelet count decreased | Investigations | MedDRA (12.0) | Systematic Assessment |
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| Weight decreased | Investigations | MedDRA (12.0) | Systematic Assessment |
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| Weight increased | Investigations | MedDRA (12.0) | Systematic Assessment |
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| White blood cell count decreased | Investigations | MedDRA (12.0) | Systematic Assessment |
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| Anorexia | Metabolism and nutrition disorders | MedDRA (12.0) | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA (12.0) | Systematic Assessment |
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| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (12.0) | Systematic Assessment |
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| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA (12.0) | Systematic Assessment |
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| Hypernatraemia | Metabolism and nutrition disorders | MedDRA (12.0) | Systematic Assessment |
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| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA (12.0) | Systematic Assessment |
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| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (12.0) | Systematic Assessment |
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| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA (12.0) | Systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (12.0) | Systematic Assessment |
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| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (12.0) | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (12.0) | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (12.0) | Systematic Assessment |
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| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA (12.0) | Systematic Assessment |
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| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (12.0) | Systematic Assessment |
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| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (12.0) | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (12.0) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (12.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Haematoma | Vascular disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (12.0) | 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
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| 1 |
|
| 2 |
|
| 3 |
|
| 4 |
|
| 5 |
|
| Blast-phase Myelofibrosis |
|
| Primary Myelofibrosis |
|
| Post-Essential Thrombocythemia (ET) Myelofibrosis |
|
| Post-Polycythemia Vera (PV) Myelofibrosis |
|
| High Risk (4 or more risk factors) |
|
| Had No Spliceosomal Mutation |
|
| Serine And Arginine Rich Splicing Factor 2 (SRSF2) |
|
| U2 Small Nuclear RNA Auxiliary Factor 1 (U2AF1) |
|
| No |
|
| Had No JAK2V617F Mutation |
|
| Unable to Determine |
|
| Had No Transfusion Dependency |
|
| Grade >=3 TEAEs |
|
| Treatment Related AEs |
|