Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Rare Diseases

Syndrome

Preleukemia

Myelodysplastic Syndromes

Neoplasm Metastasis

Myeloproliferative Disorders

Primary Myelofibrosis

Neoplastic Processes

Bone Marrow Diseases

Hematologic Diseases

Chronic Myeloproliferative Disorders

All Drugs and Chemicals

Imetelstat

Motesanib diphosphate

Enzyme Inhibitors

Protein Kinase Inhibitors

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).

Imetelstat sodium administered as IV over 2 hours with treatment as long as participants derive clinical benefit or until end of study.

Study Clinical Team

This pilot clinical trial studies how well imetelstat sodium works in treating participants with primary or secondary myelofibrosis and other myeloid malignancies. Imetelstat sodium may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To evaluate overall response rate.

SECONDARY OBJECTIVES:

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

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

III. To evaluate the efficacy of imetelstat in improving anemia or inducing red blood cell transfusion-independence in previously transfusion-dependent participants (per International Working Group for Myelofibrosis Research and Treatment \[IWG-MRT\] criteria).

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

EXPLORATORY OBJECTIVES:

I. To evaluate the effect of imetelstat on bone marrow histology, karyotype and JAK2V617F allele burden II. To evaluate the effect of imetelstat on leukocytosis, circulating blast count, circulating immature myeloid cell count and thrombocytosis.

OUTLINE: Participants receive imetelstat sodium intravenously (IV) over 2 hours on day 1. Participants may continue to receive imetelstat study treatment for as long as they derive clinical benefit or until study end. The study end when all participants discontinued study drug, the last participant enrolled has been treated for approximately 5.7 years, or imetelstat is commercially available in the United States, whichever occurs first.

Maximum duration of study was approximately 5.7 years. Arm C was never initiated, and participants allocated to Arm C (Imetelstat 9.4 mg/kg \[with MF\]) were reassigned to Arms A and B.

Imetelstat Sodium in Treating Participants With Primary or Secondary Myelofibrosis

A Pilot Open-Label Study of the Efficacy and Safety of Imetelstat (GRN163L) in Myelofibrosis and Other Myeloid Malignancies

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.

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.

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.

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.

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.

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.

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 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 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 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.

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.

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.

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.

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.

Geron Corporation

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.

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).

Arm A: Imetelstat 9.4 mg/kg (MF)

Arm B: Imetelstat 9.4 mg/kg as Induction + Maintenance (MF)

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).

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])

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).

Arm G: Imetelstat 7.5 - 9.4 mg/kg (MDS/MPN or MDS With Spliceosome Mutations or Ring Sideroblasts)

Arm D: Imetelstat 9.4 mg/kg (Blast-phase MF/Acute Myeloid Leukemia)

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

ECOG Performance Status has 5 Scores.0= Fully active, able to carry on all predisease performance without restriction;1= Restricted in physically strenuous activity but ambulatory and able to carry out work on a light/sedentary nature,2= Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours;3= Capable of only limited self-care; confined to bed/chair more than 50% of waking hours;4= Completely disabled. Cannot carry on any self-care.Totally confined to bed/chair;5= Dead. Number of participants for each score are reported.

Eastern Cooperative Oncology Group (ECOG) Performance Status Score

Myelofibrosis subtypes included MDS/MPN or MDS, blast-phase myelofibrosis, primary myelofibrosis, post-ET myelofibrosis, and Post-PV myelofibrosis. Number of participants for each subtype are reported.

Myelofibrosis subtype

DIPSS stratifies primary myelofibrosis (PMF) into four risk categories (low, intermediate 1, intermediate 2, and high risk), based on 5 clinical factors; Age\>65, Hemoglobin \<10 grams per deciliter (gm/dL), Leukocytes \>10 (9)/L, circulating blasts ≥1%, and constitutional symptoms. Participants for each status are reported. Only categories with data are reported.

Number analyzed is the number of participants with data available for DIPSS-Plus risk status.

Dynamic International Prognostic Scoring System (DIPSS)-Plus Risk Status

Spliceosome mutations represent a group of acquired genetic alterations that affect both myeloid and lymphoid malignancies.

Number analyzed is the number of participants with data available for spliceosomal mutation status.

Spliceosomal Mutation Status

Spliceosome mutations represent a group of acquired genetic alterations that affect both myeloid and lymphoid malignancies. Spliceosomal mutation type included SF3B1, SRSF2 and U2AF1. Number of participants for each type are reported.

Number analyzed is the number of participants with data available for spliceosomal mutation type.

Spliceosomal Mutation Type

Ring sideroblasts are erythroblasts with iron-loaded mitochondria visualized by Prussian blue staining (Perls' reaction) as a perinuclear ring of blue granules. Refractory anemia with ring sideroblasts (RARS) is a type of MDS that is characterized by anemia and the presence of at least 15 percent ring sideroblasts in the marrow.

Number analyzed is the number of participants with data available for ringed sideroblasts present.

Ringed Sideroblasts Present

JAK2 V617F mutation is an acquired, somatic mutation present in the majority of participants with myeloproliferative cancer (myeloproliferative neoplasms) i.e. nearly 100% of participants with polycythemia vera and in about 50% of participants with essential thrombocytosis and primary myelofibrosis.

Number analyzed is the number of participants with data available for JAK2V617F Mutation.

JAK2V617F Mutation

Transfusion dependency was defined by a history of at least 2 units of red blood cell transfusions in the last month for a hemoglobin level of less than 85 grams per deciliter (g/dL) that was not associated with clinically overt bleeding.

Transfusion Dependent

All Treated Analysis Set included all participants who received at least one dose of imetelstat.

Study Director

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.

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

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.

Blastic MF/AML Participants: Percentage of Participants With Overall Response

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.

MDS Participants: Percentage of Participants With Overall Response (Hematologic Improvement [HI] or PR or CR) Per IWG Criteria

TEAEs

Grade >=3 TEAEs

Treatment Related AEs

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

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.

Number of Participants With Spleen Response Per IWG-MRT Criteria

Arms A, B, E, F: Eligible Analysis Set included subset of all participants who received at least one dose of study drug that excludes ineligible participants who did not satisfy each and every eligibility criteria for study entry. Arm D: All Treated Analysis Set included all participants who received at least one dose of imetelstat, assessed per IWG-MRT.

MF and Blastic MF/AML Participants: Number of Participants With Transfusion Independence (CI by Anemia Response) Per IWG-MRT

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.

MDS Participants: Number of Participants With Transfusion Independence (HI by Erythroid Response) Per IWG Criteria

Eligible Analysis Set included subset of all participants who received at least one dose of study drug that excludes ineligible participants who did not satisfy each and every eligibility criteria for study entry. Data is reported for arm groups (Arms A, B, E and F) whose overall response was assessed by IWG-MRT criteria. Only responders were analyzed for this outcome measure.

MF Participants: Time to Response

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.

Blastic MF/AML Participants: Time to Response

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.

MDS Participants: Time to Response

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.

MF Participants: Duration of Response (DOR) Per IWG-MRT Criteria

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.

Blastic MF/AML Participants: Duration of Response

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.

MDS Participants: Duration of Response Per IWG Criteria

Overall Survival (OS)

Overall Study

Heart and Blood Diseases

Polycythemia Vera

Polycythemia

Thrombocytosis

Thrombocythemia, Essential

Bone Marrow Neoplasms

Hematologic Neoplasms

Blood Platelet Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Hemorrhagic Disorders

Essential Thrombocythemia

Induction dosing of 9.4 mg/kg weekly, followed by intermittent maintenance dosing.

This is a phase II open-label study of single agent imetelstat in patients with essential thrombocytopenia or with polycythemia vera who have failed or are intolerant to at least one prior therapy, or who refuse standard therapy.

For patients with ET: To obtain a preliminary estimate of efficacy of imetelstat, as measured by best hematologic response within the first year of therapy in patients with ET who have failed or are intolerant to at least one prior therapy, or who have refused standard therapy.

For patients with PV: To obtain a preliminary estimate of efficacy of imetelstat, as measured by maintenance of Hct \< 45% in men and \< 42% in women (or pre-specified Hct count that is tolerable) without phlebotomy or myelosuppressive therapy within the first year of therapy in patients with PV who have failed or are intolerant to at least one prior therapy, or who have refused standard therapy.

Open Label Study to Evaluate the Activity of Imetelstat in Patients With Essential Thrombocythemia or Polycythemia Vera

A Phase II Trial to Evaluate the Activity of Imetelstat (GRN163L) in Patients With Essential Thrombocythemia or Polycythemia Vera Who Require Cytoreduction and Have Failed or Are Intolerant to Previous Therapy, or Who Refuse Standard Therapy

Primary objectives are as follows: ET patients - best hematologic response within the first year of therapy and PV patients - maintenance of Hct \< 45% in men and \< 42% in women (or pre-specified Hct count that is tolerable) without phlebotomy or myelosuppressive therapy within the first year of therapy. Secondary objectives, to determine the durability of hematologic response and to determine the rate of phlebotomy required within the first year of therapy.

The safety and tolerability of imtelstat will be assessed by the incidence, nature, relatedness and severity of adverse events, laboratory abnormalities and vital signs.

Skin and Connective Tissue Diseases

Breast Neoplasms

Recurrence

Breast Diseases

Skin Diseases

Disease Attributes

Antineoplastic Agents

Paclitaxel

Bevacizumab

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Imetelstat is administered at a dose of 300 mg/m2 on day one of a 21 day cycle.

Imetelstat sodium

Bevacizumab is administered at 15 mg/kg on day one of a 21 day cycle

Paclitaxel is administered at 90 mg/m2 on days one and eight of a 21 day cycle

Ted Shih, PharmD

Kathy Miller, MD

The purpose of this study is to evaluate the efficacy and safety of treatment with imetelstat + paclitaxel (with or without bevacizumab) versus paclitaxel (with or without bevacizumab) alone for patients with locally recurrent or metastatic breast cancer who have not received chemotherapy or have received one non-taxane based chemotherapy for metastatic breast cancer.

Patients will be randomized in a 1:1 ratio to imetelstat + paclitaxel (with or without bevacizumab) versus paclitaxel (with or without bevacizumab) alone.

Imetelstat in Combination With Paclitaxel (With or Without Bevacizumab) in Patients With Locally Recurrent or Metastatic Breast Cancer

A Randomized Phase II Study Of Imetelstat (GRN163L) In Combination With Paclitaxel (With Or Without Bevacizumab) in Patients With Locally Recurrent Or Metastatic Breast Cancer

Defined as the time from randomization to documented disease progression, as determined by the investigator's assessment according to RECIST, or death from any cause, whichever occurs first.

Objective response as determined by the investigator according to RECIST for patients with measurable disease at baseline.

Clinical response rate includes patients with objective response and stable disease lasting at least 6 months.

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

imetelstat plus standard of care (bevacizumab or observation)

9.4 mg/kg over a 2 hour IV infusion on Day 1 and Day 8 of each 21 day cycle until disease progression.

imetelstat

Dosage and duration will be according to the FDA-approved bevacizumab package insert. Bevacizumab will be administered on Day 1 of each 21-day cycle.

Joan Schiller, MD

The purpose of this is to evaluate the efficacy and safety of imetelstat (GRN163L) as maintenance therapy for patients with advanced stage NSCLC who have not progressed after 4 cycles of platinum based therapy.

Participants will be randomized in a 2:1 ratio to imetelstat + standard of care versus standard of care alone. Participants who received bevacizumab with their induction chemotherapy will continue to receive bevacizumab on this study.

Imetelstat as Maintenance Therapy After Initial Induction Chemotherapy in Non-small Cell Lung Cancer (NSCLC)

A Randomized Phase II Study of Imetelstat as Maintenance Therapy After Initial Induction Chemotherapy for Advance Non-small Cell Lung Cancer(NSCLC)

Defined as the time from randomization to documented disease progression or death, whichever occurs earlier,as determined by the Investigator's assessment according to RECIST, or death from any cause, whichever occurs earlier.

Objective response (partial response plus complete response) occurring post-randomization as determined by the Investigator's assessment according to RECIST criteria using post-induction tumor dimensions as a baseline.

Defined as the time from the date of radomization to death from any cause during the study period.

Safety and tolerability will be assessed by the incidence, nature, and severity of adverse events, laboratory abnormalities, and vital signs.

25% dose escalation infused over 2 hours weekly

GRN163L

The purpose of this study is to determine the maximum tolerated dose (MTD) of GRN163L in combination with paclitaxel and bevacizumab in patients with locally recurrent or metastatic breast cancer (MBC)

GRN163L is a telomerase template antagonist with in vitro and in vivo activity in a variety of tumor model systems. Telomerase is an enzyme that is active primarily in tumor cells and is crucial for the indefinite growth of tumor cells. Inhibition of telomerase may result in antineoplastic effects.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Imetelstat Sodium in Treating Participants With Primary or Secondary Myelofibrosis	NCT01731951	Primary Myelofi... Secondary Myelo... Myeloid Maligna...	Imetelstat	18 Years -	Geron Corporation
Open Label Study to Evaluate the Activity of Imetelstat in Patients With Essential Thrombocythemia or Polycythemia Vera	NCT01243073	Essential Throm... Polycythemia Ve...	Imetelstat	18 Years -	Geron Corporation
Imetelstat in Combination With Paclitaxel (With or Without Bevacizumab) in Patients With Locally Recurrent or Metastatic Breast Cancer	NCT01256762	Locally Recurre...	Imetelstat sodi... Bevacizumab Paclitaxel	18 Years -	Geron Corporation
Imetelstat in Combination With Paclitaxel (With or Without Bevacizumab) in Patients With Locally Recurrent or Metastatic Breast Cancer	NCT01256762	Locally Recurre...	Imetelstat sodi... Bevacizumab Paclitaxel	18 Years -	Geron Corporation
Imetelstat as Maintenance Therapy After Initial Induction Chemotherapy in Non-small Cell Lung Cancer (NSCLC)	NCT01137968	Non-small Cell ...	imetelstat Bevacizumab	18 Years -	Geron Corporation
A Study of GRN163L With Paclitaxel and Bevacizumab to Treat Patients With Locally Recurrent Or Metastatic Breast Cancer	NCT00732056	Breast Cancer	GRN163L	18 Years -	Geron Corporation

Spots Global Cancer Trial Database for grn163l

Every month we try and update this database with for grn163l cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for grn163l

Every month we try and update this database with for grn163l cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for grn163l cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.