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Imetelstat Sodium in Treating Participants With Primary or Secondary Myelofibrosis

Sponsor
Geron Corporation (Industry)
Overall Status
Completed
CT.gov ID
NCT01731951
Collaborator
(none)
80
Enrollment
1
Location
6
Arms
66.8
Actual Duration (Months)
1.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

PRIMARY OBJECTIVES:
  1. To evaluate overall response rate.
SECONDARY OBJECTIVES:

  1. To evaluate the safety and tolerability of imetelstat (imetelstat sodium) in myelofibrosis (MF).

  2. To evaluate the efficacy of imetelstat in the reduction of spleen size, as measured by physical examination (palpable distance from the left costal margin).

  3. 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).

  4. To evaluate onset and durability of response as defined in primary and secondary endpoints

EXPLORATORY OBJECTIVES:
  1. 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.

Study Design

Study Type:
Interventional
Actual Enrollment :
80 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Pilot Open-Label Study of the Efficacy and Safety of Imetelstat (GRN163L) in Myelofibrosis and Other Myeloid Malignancies
Actual Study Start Date :
Oct 29, 2012
Actual Primary Completion Date :
May 24, 2018
Actual Study Completion Date :
May 24, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm A: Imetelstat 9.4 mg/kg (Myelofibrosis [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).

Drug: Imetelstat
Imetelstat sodium administered as IV over 2 hours with treatment as long as participants derive clinical benefit or until end of study.
Other Names:
  • GRN163L

    		•
    Experimental: 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).

    Drug: Imetelstat
    Imetelstat sodium administered as IV over 2 hours with treatment as long as participants derive clinical benefit or until end of study.
    Other Names:
  • GRN163L

    		•
    Experimental: 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).

    Drug: Imetelstat
    Imetelstat sodium administered as IV over 2 hours with treatment as long as participants derive clinical benefit or until end of study.
    Other Names:
  • GRN163L

    		•
    Experimental: 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).

    Drug: Imetelstat
    Imetelstat sodium administered as IV over 2 hours with treatment as long as participants derive clinical benefit or until end of study.
    Other Names:
  • GRN163L

    		•
    Experimental: 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).

    Drug: Imetelstat
    Imetelstat sodium administered as IV over 2 hours with treatment as long as participants derive clinical benefit or until end of study.
    Other Names:
  • GRN163L

    		•
    Experimental: 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).

    Drug: Imetelstat
    Imetelstat sodium administered as IV over 2 hours with treatment as long as participants derive clinical benefit or until end of study.
    Other Names:
  • GRN163L

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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 [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)]

      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 <upper normal limit (UNL);Neutrophil count(NC) ≥1x10^9/L and <UNL; Platelet(PLT) count ≥100x10^9/L and <UNL;<2% immature myeloid cells(IMCs), AND Clinical: Resolution of disease symptoms; Spleen and liver not palpable; No evidence of extramedullary hematopoeisis(EMH). PR:All CR criteria plus peripheral blood: Hb≥85 but <100g/L and <UNL; NC ≥1x10^9/L and <UNL; PLT count ≥50 but <100x10^9/L and <UNL;<2%IMCs. CI:achievement of anemia (≥20 g/L increase in Hb level), spleen(baseline splenomegaly palpable at 5-10 cm, below left costal margin(LCM), becomes not palpable), symptoms response (50% reduction in total symptom score) without progressive disease (PD) (appearance of new splenomegaly- palpable at least [≥]5 cm below LCM)/increase in severity of anemia, thrombocytopenia/neutropenia. Data is reported separately for arms whose response was assessed per IWG-MRT.

    2. Blastic MF/AML Participants: Percentage of Participants With Overall Response [Up to first 9 cycles of treatment (each cycle was of 28 days for Arm D)]

      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.

    3. MDS Participants: Percentage of Participants With Overall Response (Hematologic Improvement [HI] or PR or CR) Per IWG Criteria [Up to first 9 cycles of treatment (each cycle was of 28 days for Arm G)]

      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.

    Secondary Outcome Measures

    1. Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Grade >= 3 TEAEs and Treatment Related Adverse Events [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)]

      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.

    2. Number of Participants With Spleen Response Per IWG-MRT Criteria [Up to approximately 5.7 years]

      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.

    3. MF and Blastic MF/AML Participants: Number of Participants With Transfusion Independence (CI by Anemia Response) Per IWG-MRT [Up to approximately 5.7 years]

      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.

    4. MDS Participants: Number of Participants With Transfusion Independence (HI by Erythroid Response) Per IWG Criteria [Up to approximately 5.7 years]

      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.

    5. MF Participants: Time to Response [From study Day 1 to the earliest date that a response was first documented (Up to approximately 5.7 years)]

      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.

    6. Blastic MF/AML Participants: Time to Response [From study Day 1 to the earliest date that a response was first documented (Up to approximately 5.7 years)]

      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.

    7. MDS Participants: Time to Response [From study Day 1 to the earliest date that a response was first documented (Up to approximately 5.7 years)]

      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.

    8. MF Participants: Duration of Response (DOR) Per IWG-MRT Criteria [From time of initial response until documented disease progression or death whichever occurs first (Up to approximately 5.7 years)]

      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.

    9. Blastic MF/AML Participants: Duration of Response [From time of initial response until documented disease progression or death whichever occurs first (Up to approximately 5.7 years)]

      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.

    10. MDS Participants: Duration of Response Per IWG Criteria [From the time of initial response (CR/PR/HI) until documented disease progression or death whichever occurs first (Up to approximately 5.7 years)]

      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.

    11. Overall Survival (OS) [From Study Day 1 to the date of death from any cause (Up to approximately 5.7 years)]

      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.

    Eligibility Criteria

    Criteria

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

    • Diagnosis of one of the following:

    • Primary myelofibrosis (PMF) per the revised World Health Organization (WHO) criteria.

    • Post-polycythemia vera/essential thrombocythemia myelofibrosis (Post-ET/PV MF) per the International Working Group for Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria.

    • High-risk or Intermediate-2 risk MF (as defined by the Dynamic International Prognostic Scoring System [DIPSS-plus]).

    • Life expectancy of greater than or equal to (>=) 12 weeks.

    • Able to provide informed consent and be willing to sign an informed consent form.

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

    • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =<2.5 x upper limit of normal (ULN) (or =<5 x ULN if in the investigator's opinion the elevation is due to extramedullary hematopoiesis).

    • Serum glutamic pyruvate transaminase (SGPT) alanine aminotransferase (ALT) =<2.5 x ULN (or =<5 x ULN if in the investigator's opinion the elevation is due to extramedullary hematopoiesis).

    • Total bilirubin =<3.0 mg/dL (or direct bilirubin < 1 mg/dL).

    • Creatinine =<3.0 mg/dL.

    • Absolute neutrophil count >=1000/microliter (mcL).

    • Platelet count >=50,000/mcL.

    • Absence of active treatment with systemic anticoagulation and a baseline prothrombin time (PT) and activated partial thromboplastin time (aPTT) that does not exceed 1.5 x ULN.

    • Females of childbearing potential must have a negative pregnancy test =<7 days prior to registration, unless they are surgically sterile for at least 3 months (i.e., hysterectomy), OR postmenopausal for at least 12 months (follicle-stimulating hormone [FSH] >30 U/mL).

    • Females of childbearing potential must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through end of study; permitted methods for preventing pregnancy must be communicated to study participants and their understanding confirmed.

    • Males must agree to take appropriate precautions to avoid fathering a child (with at least 99% certainty) from screening through follow-up; permitted methods for preventing pregnancy should be communicated to the participants and their understanding confirmed.

    Exclusion Criteria:

    • Females who are pregnant or are currently breastfeeding.

    • Any chemotherapy (e.g., hydroxyurea), immunomodulatory drug therapy (e.g., thalidomide), immunosuppressive therapy, corticosteroids > 10 mg/day prednisone or equivalent, growth factor treatment (e.g., erythropoietin) or Janus kinase (JAK) inhibitor therapy =<14 days prior to registration.

    • Participants with another active malignancy.

    • Note: participants with early stage squamous cell carcinoma of the skin, basal cell carcinoma of the skin or cervical intraepithelial neoplasia are eligible for enrollment.

    • Known positive status for human immunodeficiency virus (HIV).

    • Any unresolved toxicity greater or equal to grade 2 from previous anticancer therapy, except for stable chronic toxicities not expected to resolve.

    • Incomplete recovery from any prior surgical procedures or had surgery =<4 weeks prior to registration, excluding the placement of vascular access.

    • Presence of acute active infection requiring antibiotics.

    • Uncontrolled intercurrent illness or any concurrent condition that, in the Investigator's opinion, would jeopardize the safety of the participant or compliance with the protocol.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Rochester Minnesota United States

    Sponsors and Collaborators

    • Geron Corporation

    Investigators

    • Study Director: Study Clinical Team, Geron Corporation

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Geron Corporation
    ClinicalTrials.gov Identifier:
    NCT01731951
    Other Study ID Numbers:
    • CR107110
    • CP14B019
    First Posted:
    Nov 22, 2012
    Last Update Posted:
    Sep 21, 2021
    Last Verified:
    Aug 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Geron Corporation
    Myelofibrosis
    Myelodysplastic Syndromes
    Myeloproliferative Neoplasm
    Imetelstat
    GRN163L
    Additional relevant MeSH terms:
    Neoplasms
    Neoplasm Metastasis
    Primary Myelofibrosis
    Imetelstat
    Motesanib diphosphate

    Study Results

    Participant Flow

    Recruitment Details 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.
    Pre-assignment Detail 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.
    Arm/Group Title Arm A: Imetelstat 9.4 mg/kg (MF) Arm B: Imetelstat 9.4 mg/kg as Induction + Maintenance (MF) Arm D: Imetelstat 9.4 mg/kg (Blast-phase MF/Acute Myeloid Leukemia) Arm E: Imetelstat 7.5 - 9.4 mg/kg (MF [With Spliceosome Mutation or Ring Sideroblasts]) Arm F: Imetelstat 7.5 - 9.4 mg/kg (MF [Without Spliceosome Mutation and Ring Sideroblasts]) Arm G: Imetelstat 7.5 - 9.4 mg/kg (MDS/MPN or MDS With Spliceosome Mutations or Ring Sideroblasts)
    Arm/Group Description 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). 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). 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). 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). 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). 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).
    Period Title: Overall Study
    STARTED 19 16 9 9 18 9
    COMPLETED 2 1 0 0 6 0
    NOT COMPLETED 17 15 9 9 12 9

    Baseline Characteristics

    Arm/Group Title Arm A: Imetelstat 9.4 mg/kg (MF) Arm B: Imetelstat 9.4 mg/kg as Induction + Maintenance (MF) Arm D: Imetelstat 9.4 mg/kg (Blast-phase MF/Acute Myeloid Leukemia) Arm E: Imetelstat 7.5 - 9.4 mg/kg (MF [With Spliceosome Mutation or Ring Sideroblasts]) Arm F: Imetelstat 7.5 - 9.4 mg/kg (MF [Without Spliceosome Mutation and Ring Sideroblasts]) Arm G: Imetelstat 7.5 - 9.4 mg/kg (MDS/MPN or MDS With Spliceosome Mutations or Ring Sideroblasts) Total
    Arm/Group Description 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). 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). 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). 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). 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). 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). Total of all reporting groups
    Overall Participants 19 16 9 9 18 9 80
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    8
    42.1%
    7
    43.8%
    6
    66.7%
    1
    11.1%
    10
    55.6%
    3
    33.3%
    35
    43.8%
    >=65 years
    11
    57.9%
    9
    56.3%
    3
    33.3%
    8
    88.9%
    8
    44.4%
    6
    66.7%
    45
    56.3%
    Sex: Female, Male (Count of Participants)
    Female
    7
    36.8%
    4
    25%
    3
    33.3%
    3
    33.3%
    7
    38.9%
    2
    22.2%
    26
    32.5%
    Male
    12
    63.2%
    12
    75%
    6
    66.7%
    6
    66.7%
    11
    61.1%
    7
    77.8%
    54
    67.5%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Not Hispanic or Latino
    19
    100%
    15
    93.8%
    8
    88.9%
    9
    100%
    17
    94.4%
    7
    77.8%
    75
    93.8%
    Unknown or Not Reported
    0
    0%
    1
    6.3%
    1
    11.1%
    0
    0%
    1
    5.6%
    2
    22.2%
    5
    6.3%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    2
    22.2%
    0
    0%
    0
    0%
    0
    0%
    2
    2.5%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    White
    19
    100%
    15
    93.8%
    6
    66.7%
    9
    100%
    17
    94.4%
    8
    88.9%
    74
    92.5%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    1
    6.3%
    1
    11.1%
    0
    0%
    1
    5.6%
    1
    11.1%
    4
    5%
    Eastern Cooperative Oncology Group (ECOG) Performance Status Score (Count of Participants)
    0
    7
    36.8%
    5
    31.3%
    2
    22.2%
    1
    11.1%
    2
    11.1%
    2
    22.2%
    19
    23.8%
    1
    11
    57.9%
    6
    37.5%
    4
    44.4%
    4
    44.4%
    13
    72.2%
    7
    77.8%
    45
    56.3%
    2
    1
    5.3%
    5
    31.3%
    3
    33.3%
    4
    44.4%
    3
    16.7%
    0
    0%
    16
    20%
    3
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    4
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    5
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Myelofibrosis subtype (Count of Participants)
    Myelodysplastic Syndromes/ Myeloproliferative Neoplasm (MDS/MPN) or MDS
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    9
    100%
    9
    11.3%
    Blast-phase Myelofibrosis
    0
    0%
    0
    0%
    8
    88.9%
    0
    0%
    0
    0%
    0
    0%
    8
    10%
    Primary Myelofibrosis
    11
    57.9%
    8
    50%
    0
    0%
    7
    77.8%
    9
    50%
    0
    0%
    35
    43.8%
    Post-Essential Thrombocythemia (ET) Myelofibrosis
    1
    5.3%
    5
    31.3%
    1
    11.1%
    2
    22.2%
    5
    27.8%
    0
    0%
    14
    17.5%
    Post-Polycythemia Vera (PV) Myelofibrosis
    7
    36.8%
    3
    18.8%
    0
    0%
    0
    0%
    4
    22.2%
    0
    0%
    14
    17.5%
    Dynamic International Prognostic Scoring System (DIPSS)-Plus Risk Status (Count of Participants)
    Intermediate-2 Risk (2 or 3 risk factors)
    11
    57.9%
    5
    31.3%
    1
    11.1%
    1
    11.1%
    10
    55.6%
    6
    66.7%
    34
    42.5%
    High Risk (4 or more risk factors)
    8
    42.1%
    11
    68.8%
    8
    88.9%
    8
    88.9%
    8
    44.4%
    2
    22.2%
    45
    56.3%
    Spliceosomal Mutation Status (Count of Participants)
    Had Spliceosomal Mutation
    7
    36.8%
    4
    25%
    5
    55.6%
    8
    88.9%
    0
    0%
    7
    77.8%
    31
    38.8%
    Had No Spliceosomal Mutation
    12
    63.2%
    11
    68.8%
    2
    22.2%
    1
    11.1%
    18
    100%
    2
    22.2%
    46
    57.5%
    Spliceosomal Mutation Type (Count of Participants)
    Splicing Factor 3B Subunit 1 (SF3B1)
    1
    5.3%
    2
    12.5%
    1
    11.1%
    1
    11.1%
    6
    33.3%
    11
    122.2%
    Serine And Arginine Rich Splicing Factor 2 (SRSF2)
    2
    10.5%
    1
    6.3%
    2
    22.2%
    4
    44.4%
    0
    0%
    9
    100%
    U2 Small Nuclear RNA Auxiliary Factor 1 (U2AF1)
    4
    21.1%
    1
    6.3%
    2
    22.2%
    3
    33.3%
    1
    5.6%
    11
    122.2%
    Ringed Sideroblasts Present (Count of Participants)
    Yes
    4
    21.1%
    2
    12.5%
    1
    11.1%
    3
    33.3%
    0
    0%
    8
    88.9%
    18
    22.5%
    No
    12
    63.2%
    10
    62.5%
    5
    55.6%
    6
    66.7%
    17
    94.4%
    1
    11.1%
    51
    63.8%
    JAK2V617F Mutation (Count of Participants)
    Had JAK2V617F Mutation
    15
    78.9%
    8
    50%
    5
    55.6%
    6
    66.7%
    14
    77.8%
    3
    33.3%
    51
    63.8%
    Had No JAK2V617F Mutation
    1
    5.3%
    5
    31.3%
    4
    44.4%
    3
    33.3%
    4
    22.2%
    6
    66.7%
    23
    28.8%
    Unable to Determine
    0
    0%
    1
    6.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.3%
    Transfusion Dependent (Count of Participants)
    Had Transfusion Dependency
    8
    42.1%
    5
    31.3%
    3
    33.3%
    2
    22.2%
    4
    22.2%
    5
    55.6%
    27
    33.8%
    Had No Transfusion Dependency
    11
    57.9%
    11
    68.8%
    6
    66.7%
    7
    77.8%
    14
    77.8%
    4
    44.4%
    53
    66.3%

    Outcome Measures

    1. Primary Outcome
    Title 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
    Description 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 <upper normal limit (UNL);Neutrophil count(NC) ≥1x10^9/L and <UNL; Platelet(PLT) count ≥100x10^9/L and <UNL;<2% immature myeloid cells(IMCs), AND Clinical: Resolution of disease symptoms; Spleen and liver not palpable; No evidence of extramedullary hematopoeisis(EMH). PR:All CR criteria plus peripheral blood: Hb≥85 but <100g/L and <UNL; NC ≥1x10^9/L and <UNL; PLT count ≥50 but <100x10^9/L and <UNL;<2%IMCs. CI:achievement of anemia (≥20 g/L increase in Hb level), spleen(baseline splenomegaly palpable at 5-10 cm, below left costal margin(LCM), becomes not palpable), symptoms response (50% reduction in total symptom score) without progressive disease (PD) (appearance of new splenomegaly- palpable at least [≥]5 cm below LCM)/increase in severity of anemia, thrombocytopenia/neutropenia. Data is reported separately for arms whose response was assessed per IWG-MRT.
    Time Frame 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)

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Arm A: Imetelstat 9.4 mg/kg (MF) Arm B: Imetelstat 9.4 mg/kg as Induction + Maintenance (MF) Arm E: Imetelstat 7.5 - 9.4 mg/kg (MF [With Spliceosome Mutation or Ring Sideroblasts]) Arm F: Imetelstat 7.5 - 9.4 mg/kg (MF [Without Spliceosome Mutation and Ring Sideroblasts])
    Arm/Group Description 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). 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). 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). 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).
    Measure Participants 19 14 9 18
    Number (95% Confidence Interval) [percentage of participants]
    36.84
    193.9%
    35.7
    223.1%
    0
    0%
    33.3
    370%
    2. Primary Outcome
    Title Blastic MF/AML Participants: Percentage of Participants With Overall Response
    Description 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.
    Time Frame Up to first 9 cycles of treatment (each cycle was of 28 days for Arm D)

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Arm D: Imetelstat 9.4 mg/kg (Blast-phase MF/Acute Myeloid Leukemia)
    Arm/Group Description 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).
    Measure Participants 9
    Number (95% Confidence Interval) [percentage of participants]
    0
    0%
    3. Primary Outcome
    Title MDS Participants: Percentage of Participants With Overall Response (Hematologic Improvement [HI] or PR or CR) Per IWG Criteria
    Description 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.
    Time Frame Up to first 9 cycles of treatment (each cycle was of 28 days for Arm G)

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Arm G: Imetelstat 7.5 - 9.4 mg/kg (MDS/MPN or MDS With Spliceosome Mutations or Ring Sideroblasts)
    Arm/Group Description 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).
    Measure Participants 9
    Number (95% Confidence Interval) [percentage of participants]
    33.3
    175.3%
    4. Secondary Outcome
    Title Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Grade >= 3 TEAEs and Treatment Related Adverse Events
    Description 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.
    Time Frame 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)

    Outcome Measure Data

    Analysis Population Description
    All Treated Analysis Set included all participants who received at least one dose of imetelstat.
    Arm/Group Title Arm A: Imetelstat 9.4 mg/kg (MF) Arm B: Imetelstat 9.4 mg/kg as Induction + Maintenance (MF) Arm D: Imetelstat 9.4 mg/kg (Blast-phase MF/Acute Myeloid Leukemia) Arm E: Imetelstat 7.5 - 9.4 mg/kg (MF [With Spliceosome Mutation or Ring Sideroblasts]) Arm F: Imetelstat 7.5 - 9.4 mg/kg (MF [Without Spliceosome Mutation and Ring Sideroblasts]) Arm G: Imetelstat 7.5 - 9.4 mg/kg (MDS/MPN or MDS With Spliceosome Mutations or Ring Sideroblasts)
    Arm/Group Description 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). 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). 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). 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). 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). 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).
    Measure Participants 19 16 9 9 18 9
    TEAEs
    100
    526.3%
    100
    625%
    100
    1111.1%
    100
    1111.1%
    100
    555.6%
    100
    1111.1%
    Grade >=3 TEAEs
    100
    526.3%
    93.5
    584.4%
    100
    1111.1%
    77.8
    864.4%
    83.3
    462.8%
    100
    1111.1%
    Treatment Related AEs
    89.5
    471.1%
    75
    468.8%
    88.9
    987.8%
    77.8
    864.4%
    83.3
    462.8%
    100
    1111.1%
    5. Secondary Outcome
    Title Number of Participants With Spleen Response Per IWG-MRT Criteria
    Description 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.
    Time Frame Up to approximately 5.7 years

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Arm A: Imetelstat 9.4 mg/kg (MF) Arm B: Imetelstat 9.4 mg/kg as Induction + Maintenance (MF) Arm D: Imetelstat 9.4 mg/kg (Blast-phase MF/Acute Myeloid Leukemia) Arm E: Imetelstat 7.5 - 9.4 mg/kg (MF [With Spliceosome Mutation or Ring Sideroblasts]) Arm F: Imetelstat 7.5 - 9.4 mg/kg (MF [Without Spliceosome Mutation and Ring Sideroblasts])
    Arm/Group Description 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). 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). 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). 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). 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).
    Measure Participants 19 14 9 9 18
    Count of Participants [Participants]
    3
    15.8%
    1
    6.3%
    1
    11.1%
    0
    0%
    2
    11.1%
    6. Secondary Outcome
    Title MF and Blastic MF/AML Participants: Number of Participants With Transfusion Independence (CI by Anemia Response) Per IWG-MRT
    Description 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.
    Time Frame Up to approximately 5.7 years

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Arm A: Imetelstat 9.4 mg/kg (MF) Arm B: Imetelstat 9.4 mg/kg as Induction + Maintenance (MF) Arm D: Imetelstat 9.4 mg/kg (Blast-phase MF/Acute Myeloid Leukemia) Arm E: Imetelstat 7.5 - 9.4 mg/kg (MF [With Spliceosome Mutation or Ring Sideroblasts]) Arm F: Imetelstat 7.5 - 9.4 mg/kg (MF [Without Spliceosome Mutation and Ring Sideroblasts])
    Arm/Group Description 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). 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). 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). 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). 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).
    Measure Participants 19 14 9 9 18
    Count of Participants [Participants]
    1
    5.3%
    0
    0%
    0
    0%
    0
    0%
    3
    16.7%
    7. Secondary Outcome
    Title MDS Participants: Number of Participants With Transfusion Independence (HI by Erythroid Response) Per IWG Criteria
    Description 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.
    Time Frame Up to approximately 5.7 years

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Arm G: Imetelstat 7.5 - 9.4 mg/kg (MDS/MPN or MDS With Spliceosome Mutations or Ring Sideroblasts)
    Arm/Group Description 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).
    Measure Participants 9
    Count of Participants [Participants]
    3
    15.8%
    8. Secondary Outcome
    Title MF Participants: Time to Response
    Description 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.
    Time Frame From study Day 1 to the earliest date that a response was first documented (Up to approximately 5.7 years)

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Arm A: Imetelstat 9.4 mg/kg (MF) Arm B: Imetelstat 9.4 mg/kg as Induction + Maintenance (MF) Arm E: Imetelstat 7.5 - 9.4 mg/kg (MF [With Spliceosome Mutation or Ring Sideroblasts]) Arm F: Imetelstat 7.5 - 9.4 mg/kg (MF [Without Spliceosome Mutation and Ring Sideroblasts])
    Arm/Group Description 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). 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). 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). 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).
    Measure Participants 7 5 0 6
    Median (Full Range) [months]
    2.1
    1.4
    2.9
    9. Secondary Outcome
    Title Blastic MF/AML Participants: Time to Response
    Description 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.
    Time Frame From study Day 1 to the earliest date that a response was first documented (Up to approximately 5.7 years)

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Arm D: Imetelstat 9.4 mg/kg (Blast-phase MF/Acute Myeloid Leukemia)
    Arm/Group Description 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).
    Measure Participants 0
    10. Secondary Outcome
    Title MDS Participants: Time to Response
    Description 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.
    Time Frame From study Day 1 to the earliest date that a response was first documented (Up to approximately 5.7 years)

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Arm G: Imetelstat 7.5 - 9.4 mg/kg (MDS/MPN or MDS With Spliceosome Mutations or Ring Sideroblasts)
    Arm/Group Description 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).
    Measure Participants 3
    Median (Full Range) [months]
    3.7
    11. Secondary Outcome
    Title MF Participants: Duration of Response (DOR) Per IWG-MRT Criteria
    Description 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.
    Time Frame From time of initial response until documented disease progression or death whichever occurs first (Up to approximately 5.7 years)

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Arm A: Imetelstat 9.4 mg/kg (MF) Arm B: Imetelstat 9.4 mg/kg as Induction + Maintenance (MF) Arm E: Imetelstat 7.5 - 9.4 mg/kg (MF [With Spliceosome Mutation or Ring Sideroblasts]) Arm F: Imetelstat 7.5 - 9.4 mg/kg (MF [Without Spliceosome Mutation and Ring Sideroblasts])
    Arm/Group Description 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). 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). 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). 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).
    Measure Participants 7 5 0 6
    Median (95% Confidence Interval) [months]
    24.36
    NA
    35.52
    12. Secondary Outcome
    Title Blastic MF/AML Participants: Duration of Response
    Description 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.
    Time Frame From time of initial response until documented disease progression or death whichever occurs first (Up to approximately 5.7 years)

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Arm D: Imetelstat 9.4 mg/kg (Blast-phase MF/Acute Myeloid Leukemia)
    Arm/Group Description 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).
    Measure Participants 0
    13. Secondary Outcome
    Title MDS Participants: Duration of Response Per IWG Criteria
    Description 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.
    Time Frame From the time of initial response (CR/PR/HI) until documented disease progression or death whichever occurs first (Up to approximately 5.7 years)

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Arm G: Imetelstat 7.5 - 9.4 mg/kg (MDS/MPN or MDS With Spliceosome Mutations or Ring Sideroblasts)
    Arm/Group Description 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).
    Measure Participants 3
    Median (95% Confidence Interval) [months]
    NA
    14. Secondary Outcome
    Title Overall Survival (OS)
    Description 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.
    Time Frame From Study Day 1 to the date of death from any cause (Up to approximately 5.7 years)

    Outcome Measure Data

    Analysis Population Description
    All Treated Analysis Set included all participants who received at least one dose of imetelstat.
    Arm/Group Title Arm A: Imetelstat 9.4 mg/kg (MF) Arm B: Imetelstat 9.4 mg/kg as Induction + Maintenance (MF) Arm D: Imetelstat 9.4 mg/kg (Blast-phase MF/Acute Myeloid Leukemia) Arm E: Imetelstat 7.5 - 9.4 mg/kg (MF [With Spliceosome Mutation or Ring Sideroblasts]) Arm F: Imetelstat 7.5 - 9.4 mg/kg (MF [Without Spliceosome Mutation and Ring Sideroblasts]) Arm G: Imetelstat 7.5 - 9.4 mg/kg (MDS/MPN or MDS With Spliceosome Mutations or Ring Sideroblasts)
    Arm/Group Description 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). 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). 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). 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). 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). 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).
    Measure Participants 19 16 9 9 18 9
    Median (95% Confidence Interval) [months]
    42.61
    26.73
    4.93
    12.09
    NA
    28.42

    Adverse Events

    Time Frame 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)
    Adverse Event Reporting Description 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.
    Arm/Group Title Arm A: Imetelstat 9.4 mg/kg (MF) Arm B: Imetelstat 9.4 mg/kg as Induction + Maintenance (MF) Arm D: Imetelstat 9.4 mg/kg (Blast-phase MF/Acute Myeloid Leukemia Arm E: Imetelstat 7.5 - 9.4 mg/kg (MF [With Spliceosome Mutation or Ring Sideroblasts]) Arm F: Imetelstat 7.5 - 9.4 mg/kg (MF [Without Spliceosome Mutation and Ring Sideroblasts]) Arm G: Imetelstat 7.5 - 9.4 mg/kg (MDS/MPN or MDS With Spliceosome Mutations or Ring Sideroblasts)
    Arm/Group Description 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). 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). 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). 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). 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). 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).
    All Cause Mortality
    Arm A: Imetelstat 9.4 mg/kg (MF) Arm B: Imetelstat 9.4 mg/kg as Induction + Maintenance (MF) Arm D: Imetelstat 9.4 mg/kg (Blast-phase MF/Acute Myeloid Leukemia Arm E: Imetelstat 7.5 - 9.4 mg/kg (MF [With Spliceosome Mutation or Ring Sideroblasts]) Arm F: Imetelstat 7.5 - 9.4 mg/kg (MF [Without Spliceosome Mutation and Ring Sideroblasts]) Arm G: Imetelstat 7.5 - 9.4 mg/kg (MDS/MPN or MDS With Spliceosome Mutations or Ring Sideroblasts)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 13/19 (68.4%) 15/16 (93.8%) 9/9 (100%) 8/9 (88.9%) 9/18 (50%) 6/9 (66.7%)
    Serious Adverse Events
    Arm A: Imetelstat 9.4 mg/kg (MF) Arm B: Imetelstat 9.4 mg/kg as Induction + Maintenance (MF) Arm D: Imetelstat 9.4 mg/kg (Blast-phase MF/Acute Myeloid Leukemia Arm E: Imetelstat 7.5 - 9.4 mg/kg (MF [With Spliceosome Mutation or Ring Sideroblasts]) Arm F: Imetelstat 7.5 - 9.4 mg/kg (MF [Without Spliceosome Mutation and Ring Sideroblasts]) Arm G: Imetelstat 7.5 - 9.4 mg/kg (MDS/MPN or MDS With Spliceosome Mutations or Ring Sideroblasts)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 17/19 (89.5%) 12/16 (75%) 9/9 (100%) 7/9 (77.8%) 14/18 (77.8%) 9/9 (100%)
    Blood and lymphatic system disorders
    Anaemia 9/19 (47.4%) 10/16 (62.5%) 8/9 (88.9%) 5/9 (55.6%) 7/18 (38.9%) 8/9 (88.9%)
    Cardiac disorders
    Atrial fibrillation 2/19 (10.5%) 1/16 (6.3%) 2/9 (22.2%) 0/9 (0%) 0/18 (0%) 0/9 (0%)
    Cardiac failure 1/19 (5.3%) 0/16 (0%) 1/9 (11.1%) 0/9 (0%) 2/18 (11.1%) 1/9 (11.1%)
    General disorders
    Fatigue 1/19 (5.3%) 1/16 (6.3%) 2/9 (22.2%) 1/9 (11.1%) 0/18 (0%) 1/9 (11.1%)
    Infections and infestations
    Lung infection 0/19 (0%) 1/16 (6.3%) 3/9 (33.3%) 1/9 (11.1%) 2/18 (11.1%) 1/9 (11.1%)
    Sepsis 0/19 (0%) 0/16 (0%) 3/9 (33.3%) 0/9 (0%) 0/18 (0%) 1/9 (11.1%)
    Investigations
    Platelet count decreased 10/19 (52.6%) 5/16 (31.3%) 8/9 (88.9%) 5/9 (55.6%) 3/18 (16.7%) 1/9 (11.1%)
    Neutrophil count decreased 4/19 (21.1%) 6/16 (37.5%) 5/9 (55.6%) 1/9 (11.1%) 3/18 (16.7%) 5/9 (55.6%)
    White blood cell count decreased 3/19 (15.8%) 6/16 (37.5%) 1/9 (11.1%) 0/9 (0%) 4/18 (22.2%) 2/9 (22.2%)
    Respiratory, thoracic and mediastinal disorders
    Epistaxis 2/19 (10.5%) 0/16 (0%) 1/9 (11.1%) 0/9 (0%) 0/18 (0%) 1/9 (11.1%)
    Other (Not Including Serious) Adverse Events
    Arm A: Imetelstat 9.4 mg/kg (MF) Arm B: Imetelstat 9.4 mg/kg as Induction + Maintenance (MF) Arm D: Imetelstat 9.4 mg/kg (Blast-phase MF/Acute Myeloid Leukemia Arm E: Imetelstat 7.5 - 9.4 mg/kg (MF [With Spliceosome Mutation or Ring Sideroblasts]) Arm F: Imetelstat 7.5 - 9.4 mg/kg (MF [Without Spliceosome Mutation and Ring Sideroblasts]) Arm G: Imetelstat 7.5 - 9.4 mg/kg (MDS/MPN or MDS With Spliceosome Mutations or Ring Sideroblasts)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 19/19 (100%) 16/16 (100%) 9/9 (100%) 9/9 (100%) 18/18 (100%) 9/9 (100%)
    Blood and lymphatic system disorders
    Anaemia 16/19 (84.2%) 9/16 (56.3%) 4/9 (44.4%) 6/9 (66.7%) 11/18 (61.1%) 7/9 (77.8%)
    Cardiac disorders
    Atrial fibrillation 2/19 (10.5%) 0/16 (0%) 1/9 (11.1%) 0/9 (0%) 0/18 (0%) 1/9 (11.1%)
    Cardiac failure 1/19 (5.3%) 1/16 (6.3%) 0/9 (0%) 0/9 (0%) 2/18 (11.1%) 2/9 (22.2%)
    Sinus tachycardia 1/19 (5.3%) 0/16 (0%) 2/9 (22.2%) 0/9 (0%) 3/18 (16.7%) 0/9 (0%)
    Eye disorders
    Eye disorders 1/19 (5.3%) 1/16 (6.3%) 1/9 (11.1%) 0/9 (0%) 4/18 (22.2%) 0/9 (0%)
    Gastrointestinal disorders
    Abdominal distension 1/19 (5.3%) 0/16 (0%) 1/9 (11.1%) 0/9 (0%) 1/18 (5.6%) 1/9 (11.1%)
    Abdominal pain 7/19 (36.8%) 1/16 (6.3%) 6/9 (66.7%) 2/9 (22.2%) 6/18 (33.3%) 0/9 (0%)
    Abdominal pain upper 1/19 (5.3%) 1/16 (6.3%) 0/9 (0%) 0/9 (0%) 1/18 (5.6%) 1/9 (11.1%)
    Constipation 4/19 (21.1%) 1/16 (6.3%) 1/9 (11.1%) 1/9 (11.1%) 1/18 (5.6%) 2/9 (22.2%)
    Diarrhoea 19/19 (100%) 15/16 (93.8%) 8/9 (88.9%) 9/9 (100%) 18/18 (100%) 9/9 (100%)
    Nausea 8/19 (42.1%) 7/16 (43.8%) 6/9 (66.7%) 1/9 (11.1%) 12/18 (66.7%) 4/9 (44.4%)
    Vomiting 7/19 (36.8%) 3/16 (18.8%) 1/9 (11.1%) 1/9 (11.1%) 5/18 (27.8%) 1/9 (11.1%)
    General disorders
    Chills 3/19 (15.8%) 2/16 (12.5%) 2/9 (22.2%) 1/9 (11.1%) 2/18 (11.1%) 0/9 (0%)
    Early satiety 4/19 (21.1%) 3/16 (18.8%) 3/9 (33.3%) 3/9 (33.3%) 1/18 (5.6%) 1/9 (11.1%)
    Fatigue 18/19 (94.7%) 15/16 (93.8%) 8/9 (88.9%) 8/9 (88.9%) 18/18 (100%) 9/9 (100%)
    Infusion related reaction 2/19 (10.5%) 3/16 (18.8%) 0/9 (0%) 0/9 (0%) 1/18 (5.6%) 1/9 (11.1%)
    Non-cardiac chest pain 2/19 (10.5%) 0/16 (0%) 1/9 (11.1%) 0/9 (0%) 1/18 (5.6%) 1/9 (11.1%)
    Oedema peripheral 7/19 (36.8%) 3/16 (18.8%) 6/9 (66.7%) 3/9 (33.3%) 5/18 (27.8%) 2/9 (22.2%)
    Pain 6/19 (31.6%) 5/16 (31.3%) 3/9 (33.3%) 2/9 (22.2%) 8/18 (44.4%) 5/9 (55.6%)
    Pyrexia 5/19 (26.3%) 2/16 (12.5%) 4/9 (44.4%) 1/9 (11.1%) 2/18 (11.1%) 1/9 (11.1%)
    Infections and infestations
    Lung infection 1/19 (5.3%) 1/16 (6.3%) 3/9 (33.3%) 1/9 (11.1%) 2/18 (11.1%) 0/9 (0%)
    Sinusitis 2/19 (10.5%) 0/16 (0%) 2/9 (22.2%) 0/9 (0%) 0/18 (0%) 1/9 (11.1%)
    Upper respiratory tract infection 1/19 (5.3%) 0/16 (0%) 0/9 (0%) 0/9 (0%) 4/18 (22.2%) 2/9 (22.2%)
    Injury, poisoning and procedural complications
    Contusion 3/19 (15.8%) 3/16 (18.8%) 1/9 (11.1%) 1/9 (11.1%) 3/18 (16.7%) 3/9 (33.3%)
    Fall 1/19 (5.3%) 1/16 (6.3%) 0/9 (0%) 0/9 (0%) 1/18 (5.6%) 1/9 (11.1%)
    Infusion related reaction 1/19 (5.3%) 1/16 (6.3%) 0/9 (0%) 0/9 (0%) 3/18 (16.7%) 1/9 (11.1%)
    Investigations
    Activated partial thromboplastin time prolonged 10/19 (52.6%) 3/16 (18.8%) 5/9 (55.6%) 2/9 (22.2%) 7/18 (38.9%) 0/9 (0%)
    Alanine aminotransferase increased 8/19 (42.1%) 3/16 (18.8%) 4/9 (44.4%) 2/9 (22.2%) 6/18 (33.3%) 5/9 (55.6%)
    Aspartate aminotransferase increased 10/19 (52.6%) 8/16 (50%) 4/9 (44.4%) 3/9 (33.3%) 6/18 (33.3%) 5/9 (55.6%)
    Blood alkaline phosphatase increased 10/19 (52.6%) 10/16 (62.5%) 3/9 (33.3%) 4/9 (44.4%) 5/18 (27.8%) 1/9 (11.1%)
    Blood amylase increased 3/19 (15.8%) 0/16 (0%) 2/9 (22.2%) 1/9 (11.1%) 2/18 (11.1%) 2/9 (22.2%)
    Blood bilirubin increased 7/19 (36.8%) 5/16 (31.3%) 1/9 (11.1%) 1/9 (11.1%) 5/18 (27.8%) 3/9 (33.3%)
    Blood creatinine increased 4/19 (21.1%) 2/16 (12.5%) 4/9 (44.4%) 0/9 (0%) 4/18 (22.2%) 4/9 (44.4%)
    Gamma-glutamyltransferase increased 2/19 (10.5%) 1/16 (6.3%) 0/9 (0%) 0/9 (0%) 4/18 (22.2%) 1/9 (11.1%)
    Lipase increased 3/19 (15.8%) 1/16 (6.3%) 3/9 (33.3%) 2/9 (22.2%) 3/18 (16.7%) 3/9 (33.3%)
    Lymphocyte count decreased 1/19 (5.3%) 1/16 (6.3%) 0/9 (0%) 0/9 (0%) 2/18 (11.1%) 1/9 (11.1%)
    Neutrophil count decreased 19/19 (100%) 16/16 (100%) 9/9 (100%) 9/9 (100%) 18/18 (100%) 9/9 (100%)
    Platelet count decreased 19/19 (100%) 16/16 (100%) 9/9 (100%) 9/9 (100%) 18/18 (100%) 9/9 (100%)
    Weight decreased 1/19 (5.3%) 4/16 (25%) 0/9 (0%) 0/9 (0%) 6/18 (33.3%) 2/9 (22.2%)
    Weight increased 1/19 (5.3%) 1/16 (6.3%) 0/9 (0%) 0/9 (0%) 2/18 (11.1%) 2/9 (22.2%)
    White blood cell count decreased 19/19 (100%) 16/16 (100%) 9/9 (100%) 9/9 (100%) 18/18 (100%) 9/9 (100%)
    Metabolism and nutrition disorders
    Anorexia 4/19 (21.1%) 5/16 (31.3%) 4/9 (44.4%) 1/9 (11.1%) 4/18 (22.2%) 2/9 (22.2%)
    Decreased appetite 1/19 (5.3%) 1/16 (6.3%) 0/9 (0%) 0/9 (0%) 3/18 (16.7%) 2/9 (22.2%)
    Hyperglycaemia 9/19 (47.4%) 10/16 (62.5%) 7/9 (77.8%) 4/9 (44.4%) 13/18 (72.2%) 7/9 (77.8%)
    Hyperkalaemia 3/19 (15.8%) 4/16 (25%) 2/9 (22.2%) 2/9 (22.2%) 3/18 (16.7%) 1/9 (11.1%)
    Hypernatraemia 0/19 (0%) 0/16 (0%) 2/9 (22.2%) 0/9 (0%) 2/18 (11.1%) 2/9 (22.2%)
    Hyperuricaemia 8/19 (42.1%) 5/16 (31.3%) 2/9 (22.2%) 2/9 (22.2%) 8/18 (44.4%) 1/9 (11.1%)
    Hypocalcaemia 4/19 (21.1%) 2/16 (12.5%) 4/9 (44.4%) 0/9 (0%) 3/18 (16.7%) 2/9 (22.2%)
    Hypoglycaemia 3/19 (15.8%) 1/16 (6.3%) 3/9 (33.3%) 0/9 (0%) 1/18 (5.6%) 0/9 (0%)
    Hypokalaemia 4/19 (21.1%) 0/16 (0%) 2/9 (22.2%) 0/9 (0%) 3/18 (16.7%) 2/9 (22.2%)
    Hyponatraemia 4/19 (21.1%) 2/16 (12.5%) 3/9 (33.3%) 0/9 (0%) 2/18 (11.1%) 2/9 (22.2%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 2/19 (10.5%) 4/16 (25%) 2/9 (22.2%) 1/9 (11.1%) 2/18 (11.1%) 2/9 (22.2%)
    Back pain 5/19 (26.3%) 4/16 (25%) 1/9 (11.1%) 1/9 (11.1%) 3/18 (16.7%) 4/9 (44.4%)
    Bone pain 5/19 (26.3%) 1/16 (6.3%) 0/9 (0%) 1/9 (11.1%) 2/18 (11.1%) 0/9 (0%)
    Muscular weakness 1/19 (5.3%) 1/16 (6.3%) 0/9 (0%) 0/9 (0%) 3/18 (16.7%) 2/9 (22.2%)
    Musculoskeletal pain 2/19 (10.5%) 1/16 (6.3%) 0/9 (0%) 0/9 (0%) 1/18 (5.6%) 1/9 (11.1%)
    Myalgia 3/19 (15.8%) 2/16 (12.5%) 2/9 (22.2%) 1/9 (11.1%) 1/18 (5.6%) 0/9 (0%)
    Neck pain 0/19 (0%) 0/16 (0%) 1/9 (11.1%) 0/9 (0%) 1/18 (5.6%) 2/9 (22.2%)
    Pain in extremity 3/19 (15.8%) 3/16 (18.8%) 3/9 (33.3%) 1/9 (11.1%) 2/18 (11.1%) 2/9 (22.2%)
    Nervous system disorders
    Dizziness 3/19 (15.8%) 0/16 (0%) 3/9 (33.3%) 1/9 (11.1%) 0/18 (0%) 1/9 (11.1%)
    Headache 4/19 (21.1%) 2/16 (12.5%) 0/9 (0%) 0/9 (0%) 3/18 (16.7%) 2/9 (22.2%)
    Peripheral sensory neuropathy 2/19 (10.5%) 0/16 (0%) 1/9 (11.1%) 1/9 (11.1%) 0/18 (0%) 0/9 (0%)
    Psychiatric disorders
    Anxiety 0/19 (0%) 2/16 (12.5%) 1/9 (11.1%) 0/9 (0%) 2/18 (11.1%) 1/9 (11.1%)
    Insomnia 3/19 (15.8%) 2/16 (12.5%) 2/9 (22.2%) 0/9 (0%) 1/18 (5.6%) 2/9 (22.2%)
    Respiratory, thoracic and mediastinal disorders
    Cough 5/19 (26.3%) 1/16 (6.3%) 4/9 (44.4%) 3/9 (33.3%) 5/18 (27.8%) 2/9 (22.2%)
    Dyspnoea 5/19 (26.3%) 2/16 (12.5%) 7/9 (77.8%) 2/9 (22.2%) 5/18 (27.8%) 2/9 (22.2%)
    Epistaxis 5/19 (26.3%) 3/16 (18.8%) 1/9 (11.1%) 1/9 (11.1%) 4/18 (22.2%) 1/9 (11.1%)
    Pulmonary hypertension 3/19 (15.8%) 0/16 (0%) 0/9 (0%) 0/9 (0%) 1/18 (5.6%) 1/9 (11.1%)
    Skin and subcutaneous tissue disorders
    Alopecia 1/19 (5.3%) 3/16 (18.8%) 2/9 (22.2%) 0/9 (0%) 1/18 (5.6%) 2/9 (22.2%)
    Hyperhidrosis 1/19 (5.3%) 1/16 (6.3%) 0/9 (0%) 1/9 (11.1%) 2/18 (11.1%) 2/9 (22.2%)
    Night sweats 0/19 (0%) 2/16 (12.5%) 1/9 (11.1%) 0/9 (0%) 1/18 (5.6%) 1/9 (11.1%)
    Pruritus 5/19 (26.3%) 1/16 (6.3%) 0/9 (0%) 1/9 (11.1%) 4/18 (22.2%) 0/9 (0%)
    Vascular disorders
    Haematoma 1/19 (5.3%) 2/16 (12.5%) 1/9 (11.1%) 0/9 (0%) 0/18 (0%) 0/9 (0%)
    Hypertension 1/19 (5.3%) 0/16 (0%) 0/9 (0%) 0/9 (0%) 5/18 (27.8%) 2/9 (22.2%)
    Hypotension 1/19 (5.3%) 0/16 (0%) 3/9 (33.3%) 0/9 (0%) 1/18 (5.6%) 1/9 (11.1%)

    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

    Results Point of Contact

    Name/Title Study Director
    Organization Geron Corp.
    Phone 650-473-7700
    Email myf2001-info@geron.com
    Responsible Party:
    Geron Corporation
    ClinicalTrials.gov Identifier:
    NCT01731951
    Other Study ID Numbers:
    • CR107110
    • CP14B019
    First Posted:
    Nov 22, 2012
    Last Update Posted:
    Sep 21, 2021
    Last Verified:
    Aug 1, 2021