A Study Comparing Imetelstat Versus Best Available Therapy for the Treatment of Intermediate-2 or High-risk Myelofibrosis (MF) Who Have Not Responded to Janus Kinase (JAK)-Inhibitor Treatment

A Randomized Open-Label, Phase 3 Study to Evaluate Imetelstat (GRN163L) Versus Best Available Therapy (BAT) in Patients With Intermediate-2 or High-risk Myelofibrosis (MF) Relapsed / Refractory (R/R) to Janus Kinase (JAK) Inhibitor

The purpose of the study is to evaluate the overall survival of participants treated with imetelstat compared to best available therapy with intermediate-2 or high-risk Myelofibrosis (MF) who are relapsed/refractory (R/R) to Janus Kinase (JAK)-Inhibitor treatment.

Study Overview

• Status: Active, not recruiting
• Conditions: Myelofibrosis
• Intervention / Treatment: Drug: Best Available Therapy (BAT); Drug: Imetelstat

Detailed Description

This is a multicenter study with 2 arms, and will include 3 phases: a) screening phase of up to 28 days before randomization during which participants will complete a 14-day washout period from all prior therapies including JAK-inhibitor treatment, and the participant's eligibility will be reviewed; b) treatment phase, from randomization until study treatment (imetelstat or BAT) discontinuation; and c) post treatment follow-up phase, that begins when the participant discontinues treatment, and will continue until death, lost to follow-up, withdrawal of consent, or study end, whichever occurs first. Participants will be randomized (2:1) into 2 Arms (Arm A will receive imetelstat and Arm B will receive BAT).

Participants who meet progressive disease criteria and discontinue BAT, may crossover to receive imetelstat treatment after sponsor's approval.

• Study Type: Interventional
• Enrollment (Actual): 327
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Córdoba, Argentina, X5000JHQ
    • Sanatorio Allende
  • Buenos Aires
    • Ciudad de Buenos Aires, Buenos Aires, Argentina, C118AAT
      • Hospital Aleman
  • Santa Fe Province
    • Rosario, Santa Fe Province, Argentina, S2000ORE
      • Sanatorio de la Mujer
• Australia
  • New South Wales
    • St Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
  • Queensland
    • Herston, Queensland, Australia, 4011
      • Royal Brisbane and Women's Hospital
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Royal Hobart Hospital
  • Victoria
    • Richmond, Victoria, Australia, 3121
      • Epworth Healthcare
• Austria
  • Burgenland
    • Wein, Burgenland, Austria, 1130
      • Krankenhaus Hietzing mit Neurologischem Zentrum Rosenhügel
  • Upper Austria
    • Linz, Upper Austria, Austria, 4020
      • Krankenhaus der Elisabethinen
    • Linz, Upper Austria, Austria, 4021
      • Kepler Universitätsklinikum Gm
    • Wels, Upper Austria, Austria, 4600
      • Klinikum Wels-Grieskirchen GmbH
• Belgium
  • Jette, Belgium
    • Universitair Ziekenhuis Brussel - Myeloom Centrum Brussel (MCB)
  • Antwerpen
    • Antwerp, Antwerpen, Belgium, 2930
      • AZ Klina
    • Edegem, Antwerpen, Belgium, 2650
      • UZ Antwerpen
  • Hainaut
    • Haine-Saint-Paul, Hainaut, Belgium, 7100
      • Centre Hospitalier de Jolimont
  • Oost-Vlaanderen
    • Ghent, Oost-Vlaanderen, Belgium, 9000
      • Universitair Ziekenhuis Gent
• Brazil
  • Florianópolis, Brazil, 88034-000
    • CEPON Centro de Pesquisas Oncologicas SC
  • São Paulo, Brazil
    • Hospital A.C.Camargo Cancer Center - Clinical Oncology
  • Ceará
    • Fortaleza, Ceará, Brazil, 60135285
      • Centro de oncologia Leonardo da Vinci
  • Goiás
    • Goiânia, Goiás, Brazil, 74605
      • Hospital das Clínicas UFG
  • Paraná
    • Curitiba, Paraná, Brazil, 81520-060
      • Hospital Erasto Gaertner
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
      • Hospital de Clinicas de Porto Alegre - UFRGS
    • Porto Alegre, Rio Grande do Sul, Brazil, 90470340
      • Centro Gaucho Integrado de Oncologia, Hematologia, Ensino e Pesquisa Ltda
  • São Paulo
    • São Paulo, São Paulo, Brazil, 01323000
      • Instituto de Educação, Pesquisa e Gestão em Saúde
    • São Paulo, São Paulo, Brazil, 05651-901
      • Hospital Israelita Albert Einstein
    • São Paulo, São Paulo, Brazil, 17210-120
      • Fundacao Doutor Amaral Carvalho / Hospital Amaral Carvalho
• Bulgaria
  • Plovdiv
    • Plovdiv, Plovdiv, Bulgaria, 4002
      • UMBAL Sveti Georgi
  • Sofia
    • Sofia, Sofia, Bulgaria, 1756
      • Specialized Hospital for Active Therapy of Hematological dis
• Colombia
  • Antioquia, Colombia
    • Hospital Pablo Tobon Uribe
  • Cali, Colombia, 760042
    • Centro Medico Imbanaco de Cali S.A.
  • Risaralda Department
    • Pereira, Risaralda Department, Colombia, 660000
      • Oncologos del Occidente S.A
• Denmark
  • Odense, Denmark, DK-5000 C
    • Odense University Hospital - Hematology
• France
  • Brest, France, 29609
    • CHRU Brest - Hopital Morvan
  • Paris, France, 75010
    • CHU - Hôpital Saint Louis - Centre D'Investigations Cliniq
  • Auvergne-Rhône-Alpes
    • Pierre-Bénite, Auvergne-Rhône-Alpes, France, 69495
      • Centre Hospitalier Lyon
  • Indre-et-Loire
    • Tours, Indre-et-Loire, France, 37044
      • Chu Bretonneau
  • Le Kremlin-Bicêtre
    • Paris, Le Kremlin-Bicêtre, France, 94270
      • Hôpital Bicêtre
  • Loire-Atlantique
    • Nantes, Loire-Atlantique, France, 44000
      • CHU de Nantes - Hematologie
  • Nice Cedex 3
    • Nice, Nice Cedex 3, France, 06202
      • CHU de Nice - Hopital de l'Archet II - Pharmacie
  • Provence-Alpes-Côte d'Azur Region
    • Avignon, Provence-Alpes-Côte d'Azur Region, France, 84902
      • Hospital CENTRE HOSPITALIER AVIGNON
  • Sarthe
    • Le Mans, Sarthe, France, 72037
      • Centre Hospitalier Du Mans - Cancérologie Médicale
  • Île-de-France Region
    • Paris, Île-de-France Region, France, 75679
      • Hopital Cochin - Aphp Hôpitaux Universitaires Paris Centre
• Georgia
  • Tbilisi, Georgia, 0112
    • LTD Israeli-Georgian Medical R
  • Tbilisi, Georgia, 0112
    • M.Zodelava Hematology Center L
  • Tbilisi, Georgia, 0179
    • Multi Profile Clinic Consilium
  • K'alak'i T'bilisi
    • Tbilisi, K'alak'i T'bilisi, Georgia, 0159
      • J.S.C."K.Eristavi National Cen
    • Tbilisi, K'alak'i T'bilisi, Georgia, 186
      • Ltd "Medinvest - Institute of Hematology and Trans
• Germany
  • Baden-Wurttemberg
    • Mannheim, Baden-Wurttemberg, Germany, 68167
      • Universitätsklinikum Mannheim - University of Heidelberg
    • Tübingen, Baden-Wurttemberg, Germany, 72076
      • Universitätsklinikum Tübingen
  • Hamburg
    • Dresden, Hamburg, Germany, 1307
      • Universitätsklinikum Carl Gust
  • Rhineland-Palatinate
    • Kempten, Rhineland-Palatinate, Germany, 87439
      • Klinikum Kempten-Oberallgaeu GmbH
  • Saxony
    • Leipzig, Saxony, Germany, 04103
      • Universitätsklinikum Leipzig AöR
  • Saxony-Anhalt
    • Halle, Saxony-Anhalt, Germany, 6120
      • Martin-Luther-Universität Halle-Wittenberg
• Hungary
  • Nyíregyháza, Hungary, 4400
    • Szabolcs-Szatmár-Bereg Megyei Önkormányzat Jósa András
• India
  • Hyderabad, India, 560099
    • Narayana Hrudayalaya Hospital
  • Pune, India
    • Sahyadri Specialty Hospital
  • Pune, India, 411004
    • Deenanath Mangeshkar Hospital & Research Center
  • Gujarat
    • Surat, Gujarat, India, 395002
      • Nirmal Hospital - Hematology
  • Karnataka
    • Bangalore, Karnataka, India, 560 034
      • St. John's Medical College Hospital
    • Bengaluru, Karnataka, India, 560076
      • Fortis Hospital 154/9
  • National Capital Territory of Delhi
    • New Delhi, National Capital Territory of Delhi, India, 110060
      • Sir Ganga Ram Hospital
    • New Delhi, National Capital Territory of Delhi, India, 110029
      • All India Institute of Medical Sciences, Dept. of Hematology, New Delhi (All India Institute Of Medical Sciences)
  • New Delhi
    • Gurgaon, New Delhi, India, 122002
      • Fortis Memorial Research Institute
  • Odisha
    • Bhubaneswar, Odisha, India, 751019
      • All India Institute of Medical Sciences
  • West Bengal
    • Kolkata, West Bengal, India, 700014
      • Nilratan Sircar Medical College
• Israel
  • Beersheba, Israel, 84101
    • Soroka Medical Center - Hematology Institute
  • Haifa, Israel, 31048
    • Bnai Zion Medical Center
  • Haifa, Israel, 3436212
    • Carmel MC
  • Central District
    • Rehovot, Central District, Israel, 7610001
      • Kaplan Medical Center
    • Ẕerifin, Central District, Israel, 7030000
      • Shamir Medical Center (Assaf Harofeh)
  • Jerusalem
    • Jerusalem, Jerusalem, Israel, 9112001
      • Hadassah Medical Organization
  • Northern District
    • Nahariya, Northern District, Israel, 22100
      • Western Galilee Hospital - Nahariya
  • Southern District
    • Ashdod, Southern District, Israel, 7747629
      • Assuta Ashdod University Hospi
    • Ashkelon, Southern District, Israel, 78278
      • Barzilai Medical Center
• Italy
  • Catania, Italy, 95122
    • Presidio Ospedaliero Garibaldi
  • Meldola, Italy, 47014
    • Irccs Irst
  • Milan, Italy, 20132
    • Ospedale San Raffaele
  • Milan, Italy, 20162
    • ASST Grande Ospedale Metropoli
  • Monza, Italy, 20900
    • Azienda Ospedaliera San Gerard
  • Napoli, Italy, 80122
    • AOU Federico II
  • Roma, Italy, 00144
    • ASL Roma 2 - PO "S. Eugenio"
  • Alessandria
    • Alessandria, Alessandria, Italy, 15121
      • PO Civile SS.Antonio e Biagio
  • Bologna
    • Bologna, Bologna, Italy, 40138
      • A.O.di Bologna Policl.S.Orsola
  • Ferrara
    • Cona, Ferrara, Italy, 44124
      • Arcispedale S.Anna - Ematologi
  • Firenze
    • Florence, Firenze, Italy, 50134
      • AOU Careggi
  • Genova
    • Genova, Genova, Italy, 16132
      • IRCCS Ospedale Policlinico San Martino
    • Genova, Genova, Italy, 6- 16132
      • Clinica Ematologica, Univ. Deg
  • Milano
    • Milan, Milano, Italy, 20122
      • Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
  • Ravenna
    • Ravenna, Ravenna, Italy, 48121
      • Ospedale Civile S.Maria delle Croci, AUSL Ravenna
  • Reggio Calabria
    • Reggio Calabria, Reggio Calabria, Italy, 42123
      • Arcispedale S Maria Nuova, AO di Reggio Emilia
    • Reggio Calabria, Reggio Calabria, Italy, 89124
      • Azienda Ospedaliera Bianchi-Me
  • Rimini
    • Rimini, Rimini, Italy, 47900
      • AUSL di Rimini Ospedale Infermi di Rimini
  • Roma
    • Roma, Roma, Italy, 00168
      • Policlinico Universitario Agostino Gemelli
  • Torino
    • Orbassano, Torino, Italy, 10043
      • AOU San Luigi Gonzaga
    • Torino, Torino, Italy, 10126
      • AOU Città della Salute e della Scienza di Torino
  • Varese
    • Varese, Varese, Italy, 21100
      • Ospedale di Circolo, PO Varese
  • Vicenza
    • Vicenza, Vicenza, Italy, 36100
      • Ospedale S.Bortolo, AULSS n.6
• Malaysia
  • Georgetown
    • Pulau Pinang, Georgetown, Malaysia, 10990
      • Hospital Pulau Pinang
  • Johor
    • Johor Bahru, Johor, Malaysia, 80000
      • Hospital Sultanah Aminah Johor Bahru
  • Kelantan
    • Kota Bharu, Kelantan, Malaysia, 15586
      • Hospital Raja Perempuan Zainab II
  • Sarawak
    • Kuching, Sarawak, Malaysia, 93586
      • Sarawak General Hospital
  • Selangor
    • Ampang, Selangor, Malaysia, 68000
      • Hospital Ampang
• Poland
  • Biała Podlaska, Poland, 21-500
    • Wojewodzki Szpital Specjalistyczny
  • Greater Poland Voivodeship
    • Piła, Greater Poland Voivodeship, Poland, 64-920
      • Ars Medical sp. z o.o.
    • Skórzewo, Greater Poland Voivodeship, Poland, 60-185
      • Centrum Medyczne Pratia Poznan
  • Silesian Voivodeship
    • Katowice, Silesian Voivodeship, Poland, 40-519
      • Pratia Onkologia Katowice
• Portugal
  • Lisbon, Portugal, 1495-005
    • H. São Francisco Xavier-Centro
  • Braga District
    • Braga, Braga District, Portugal, 4710-243
      • CCA-Braga. Centro Clínico Académico - Hospital Braga
  • Lisbon District
    • Lisbon, Lisbon District, Portugal, 1400-038
      • Centro Clinico Fundacao Champalimaud
    • Lisbon, Lisbon District, Portugal, 1649-035
      • H. Santa Maria. Centro Hospita
• Russia
  • Omsk, Russia, 644013
    • Budgetary Healthcare Institution of Omsk Region
  • Saratov, Russia, 410012
    • GOU VPO Saratov State Medical University n.a. V.I.
  • Moscow Oblast
    • Moscow, Moscow Oblast, Russia, 129110
      • MONIKI - Oncology
  • Novosibirsk Oblast
    • Novosibirsk, Novosibirsk Oblast, Russia, 630091
      • MUZ City Clinical Hospital # 2
• Singapore
  • Central Singapore
    • Singapore, Central Singapore, Singapore, 119074
      • National University Cancer Institute (NCIS)
    • Singapore, Central Singapore, Singapore, 169608
      • Singapore General Hospital
• South Korea
  • Busan, South Korea, 49241
    • Pusan National University Hospital - Hematology and Oncology
  • Seongdong, South Korea, 6591
    • The Catholic University of Korea
  • Seoul, South Korea, 3722
    • Severance Hospital, Yonsei Uni
  • Busan Gwang'Yeogsi [Pusan-Kwangyokshi]
    • Busan, Busan Gwang'Yeogsi [Pusan-Kwangyokshi], South Korea, 47392
      • Inje University Busan Paik Hos
    • Busan, Busan Gwang'Yeogsi [Pusan-Kwangyokshi], South Korea, 48108
      • Inje University Haeundae Paik Hospital
  • Gyeonggido
    • Goyang-si, Gyeonggido, South Korea, 10408
      • National Cancer Institute Center for Cancer Research
  • Incheon Gwang'Yeogsi [Inch'n-Kwangyokshi]
    • Incheon, Incheon Gwang'Yeogsi [Inch'n-Kwangyokshi], South Korea, 21565
      • Gachon University Gil Medical Center
  • Seoul Teugbyeolsi [Seoul-T'Ukp
    • Seoul, Seoul Teugbyeolsi [Seoul-T'Ukp, South Korea, 03080
      • Seoul National University Hospital - Department of Internal
  • Seoul Teugbyeolsi [Seoul-T'Ukpyolshi]
    • Seoul, Seoul Teugbyeolsi [Seoul-T'Ukpyolshi], South Korea, 02841
      • Korea University Anam Hospital
    • Seoul, Seoul Teugbyeolsi [Seoul-T'Ukpyolshi], South Korea, 08308
      • Korea University Guro Hospital
    • Seoul, Seoul Teugbyeolsi [Seoul-T'Ukpyolshi], South Korea, 6351
      • Samsung Medical Center
    • Seoul, Seoul Teugbyeolsi [Seoul-T'Ukpyolshi], South Korea, 06273
      • Gangnam Severance Hospital, Yonsei University Health System
• Spain
  • Madrid, Spain, 28040
    • Hospital Universitario Fundaci
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanco
  • Alicante
    • Alicante, Alicante, Spain, 03010
      • H.G.U. Alicante
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Institut Català d'Oncologia-Ho
    • Sabadell, Barcelona, Spain, 08208
      • C.S. Parc Tauli
  • Canary Islands
    • Las Palmas de Gran Canaria, Canary Islands, Spain, 35019
      • Hospital Universitario de Gran
  • Cáceres
    • Cáceres, Cáceres, Spain, 10003
      • H. San Pedro de Alcántara
  • Girona
    • Girona, Girona, Spain, 17007
      • ICO-Hospital Universitari de G
  • Granada
    • Granada, Granada, Spain, 18014
      • Hospital Universitario Virgen
  • Madrid
    • Madrid, Madrid, Spain, 28041
      • Hospital U. 12 Octubre
    • Madrid, Madrid, Spain, 28046
      • H.U. La Paz
  • Málaga
    • Málaga, Málaga, Spain, 29010
      • H.U.V. de la Victoria
  • Valencia
    • Alzira, Valencia, Spain, 46600
      • H.U. Ribera de Alzira
  • Zaragoza
    • Zaragoza, Zaragoza, Spain, 50012
      • H. Quirón Zaragoza
• Taiwan
  • Taichung, Taiwan, 404
    • China Medical University Hospital - Hematology/Onc
  • Chiayi
    • Chiayi City, Chiayi, Taiwan, 613
      • Chang Gung Medical Foundation
  • Taipei
    • Taipei, Taipei, Taiwan, 11490
      • Tri-Service General Hospital
• Turkey (Türkiye)
  • Adapazarı, Turkey (Türkiye), 54100
    • Sakarya Research and Training Hospital - Medical Oncology
  • Ankara, Turkey (Türkiye), 06560
    • Gazi University Medical Faculty
  • Ankara
    • Ankara, Ankara, Turkey (Türkiye), 6590
      • Ankara University Medical Facu
  • Istanbul
    • Istanbul, Istanbul, Turkey (Türkiye), 34098
      • Istanbul Universitesi Cerrahpasa
    • Istanbul, Istanbul, Turkey (Türkiye), 34214
      • Medipol Bagcilar Mega Hospital
    • Istanbul, Istanbul, Turkey (Türkiye), 34899
      • Marmara University Pendik Training and Research Hospital
  • Mersin
    • Mersin, Mersin, Turkey (Türkiye)
      • Medical Park Mersin Hastanesi
  • İzmir
    • Izmir, İzmir, Turkey (Türkiye), 35100
      • Ege Universitesi Tip Fakultesi
• United Kingdom
  • London, United Kingdom, EC1A 7BE
    • St Bartholomew's Hospital
  • London, United Kingdom, SE1 9RT
    • Guys and St Thomas' Hospital
  • Oxford, United Kingdom, OX3 9DS
    • Oxford University Hospitals
• United States
  • California
    • La Jolla, California, United States, 92093-1503
      • University of California-San Diego/Moores UCSD Cancer Center
    • Los Angeles, California, United States, 90096
      • UCLA David Geffen School of Medicine
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Smilow Cancer Center at YNHH
  • Florida
    • Plantation, Florida, United States, 33326
      • BRCR Medical Center Inc
    • Tampa, Florida, United States, 33612
      • University of South Florida
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Norton Cancer Institute
  • Louisiana
    • New Orleans, Louisiana, United States, 70124
      • Ochsner Clinic Foundation
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Maryland Oncology Hematology
  • New York
    • New York, New York, United States, 10029
      • Icahn School Of Medicine At Mount Sinai
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center
  • South Dakota
    • Watertown, South Dakota, United States, 57201
      • Prairie Lakes Health Care System, Inc.
  • Texas
    • Houston, Texas, United States, 77024
      • Oncology Consultants
    • Houston, Texas, United States, 77030-4000
      • The University of Texas MD
  • Utah
    • Ogden, Utah, United States, 84405
      • Community Cancer Trials of Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists
  • Virginia
    • Fredericksburg, Virginia, United States, 22408
      • Hematology Oncology Associates of Fredericksburg
  • Washington
    • Seattle, Washington, United States, 98405
      • Northwest Medical Specialties PLLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of primary myelofibrosis according to the revised World Health Organization criteria or post-essential thrombocythemia-MF or post-polycythemia vera-MF according to the IWG-MRT criteria
• Dynamic International Prognostic Scoring System intermediate-2 or high-risk MF

• Relapsed/refractory to JAK-inhibitor treatment as defined in either inclusion (i), (ii) or (iii) and not eligible for allogeneic stem cell transplantation (ASCT) at screening:

  • (i) Treatment with JAK-inhibitor for >= 6 months duration, including at least 2 months at an optimal dose as assessed by the investigator for that participant and at least one of the following:

    1. no decrease in spleen volume (< 10% by MRI or CT) from the start of treatment with JAK-inhibitor
    2. no decrease in spleen size (< 30% by palpation or length by imaging) from the start of treatment with JAK-inhibitor
    3. no decrease in symptoms (< 20% by Myelofibrosis Symptom Assessment Form [MFSAF] or myeloproliferative neoplasm SAF) from the start of treatment with JAK-inhibitor
    4. a score of at least 15 on TSS assessed using the MFSAF v4.0 during screening.
  • (ii) Treatment with JAK-inhibitor treatment for>= 3 months duration with maximal doses (e.g., 20-25 mg twice daily ruxolitinib) for that participant and no decrease in spleen volume/size or symptoms as defined in inclusion criterion (i [a, b, or c]).

  • (iii) Following maximum tolerated doses of JAK inhibitor therapy for ≥3 months duration, having documented relapsed disease defined as either

    1. Increase in spleen volume from time of best response by 25% measured by MRI or CT, or

    2. Increase in spleen size by palpation, CT, or ultrasound

       • (b.i) For splenomegaly of 5-10 cm at the start of JAK inhibitor treatment, at least 100% increase in palpable spleen size from time of best response;
       • (b.ii) For splenomegaly of > 10 cm at the start of JAK inhibitor treatment, at least 50% increase in palpable spleen size from time of best response;

AND not a candidate for further JAK inhibitor at screening per investigator.

• Measurable splenomegaly demonstrated by a palpable spleen measuring >= 5 cm below the left costal margin or a spleen volume >= 450 cm^3 by MRI or CT
• Active symptoms of MF on the MFSAF v4.0 demonstrated by a symptom score of at least 5 points (on a 0 to 10 scale)
• Hematology laboratory test values within the protocol defined limits
• Biochemical laboratory test values must be within protocol defined limits
• Eastern Cooperative Oncology Group Performance Status score of 0, 1, or 2
• Participants should follow protocol defined contraceptives procedures
• A woman of childbearing potential must have a negative serum or urine pregnancy test at screening

Exclusion Criteria:

• Peripheral blood blast count of >= 10% or bone marrow blast count of >=10%
• Known allergies, hypersensitivity, or intolerance to imetelstat or its excipients
• Prior treatment with imetelstat
• Any chemotherapy or MF directed therapy, including investigational drug regardless of class or mechanism of action, immunomodulatory or immunosuppressive therapy, corticosteroids greater than 30 mg/day prednisone or equivalent, and JAK-inhibitor treatment less than equal to 14 days prior to randomization

• Diagnosis or treatment for malignancy other than MF except:

  • Malignancy treated with curative intent and with no known active disease present for >= 3 years before randomization
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  • Adequately treated cervical carcinoma in situ without evidence of disease
• Known history of human immunodeficiency virus or any uncontrolled active systemic infection requiring IV antibiotics
• Active systemic hepatitis infection requiring treatment (carriers of hepatitis virus are permitted to enter the study), or any known acute or chronic liver disease requiring treatment unless related to underlying hepatosplenomegaly due to MF
• Major surgery within 28 days prior to randomization
• Any life-threatening illness (e.g., coronavirus disease-2019), medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the participant's safety, interfere with the imetelstat metabolism, or put the study outcomes at undue risk

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Best Available Therapy (BAT); Participants will receive BAT (investigator-selected non-JAK-inhibitor treatment), until disease progression or unacceptable toxicity, treatment discontinuation or study end. Participants on BAT who meet protocol-defined criteria for progressive disease may crossover to receive imetelstat treatment after sponsor's approval.	Drug: Best Available Therapy (BAT); Non-JAK-inhibitor treatment will be given, which may include but is not limited to hydroxyurea, thalidomide or an analog of thalidomide, interferon, danazol, hypomethylating agents, chemotherapy or radiotherapy.
Experimental: Imetelstat; Participants will receive imetelstat sodium at 9.4 mg/kg intravenous (IV) every 21 days (±3 days), until disease progression or unacceptable toxicity, treatment discontinuation or study end.	Drug: Imetelstat; Imetelstat sodium will be given intravenously at 9.4 mg/kg every 21 days, until disease progression or unacceptable toxicity, treatment discontinuation or study end.; Other Names: GRN163L

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Overall survival is defined as the time interval from randomization date to date of death from any cause.	Baseline (Day 1) until End of Study (EOS) (approximately 3 years )]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptom response rate	The proportion of participants achieving a ≥50% reduction in Total Symptom Score (TSS) measured at Week 24 compared to baseline	Baseline (Day 1), and at Week 24
Progression-free survival	Progression-free survival is defined as the time interval from randomization date to the first date of disease progression (worsening splenomegaly or leukemic transformation per 2013 International Working Group - Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria) or death from any cause, whichever occurs first.	Baseline (Day 1) until End of Study (EOS) (approximately 3 years)
Spleen response rate	The proportion of participants who achieve a reduction in spleen volume of ≥ 35% from baseline at Week 24.	Baseline (Day 1), and at Week 24
Complete remission (CR), partial remission (PR), clinical improvement (CI), spleen response, symptoms response, and anemia response per modified 2013 IWG-MRT criteria	The proportion of participants achieving CR or PR, CI, spleen response, symptom response, and anemia response per modified 2013 IWG-MRT criteria.	Baseline (Day 1) until End of Treatment (approximately 3 years)
Reduction in the degree of bone marrow fibrosis	Reduction in the degree of bone marrow fibrosis will be assessed.	Baseline (Day 1) until End of Treatment (approximately 3 years)
Number of Participants with Adverse Events	Safety will be assessed based on the incidence and severity (according to the Common Terminology Criteria for Adverse Events) of treatment emergent adverse events from the time of randomization until 30 days after completion of treatment	Screening (Day -28 to -1) until End of Study (approximately 3 years)
Assessment of Cmax	Maximum Observed Plasma Concentration (Cmax).	Day 1 of all cycles (each cycle is 21 days)
Assessment of Tmax	Time to reach the maximum observed plasma concentration	Day 1 of all cycles (each cycle is 21 days)
Assessment of t1/2	Elimination half-life.	Day 1 of all cycles (each cycle is 21 days)
Assessment of AUC	Area under the drug concentration-plasma time curve (AUC) from time zero to last measurable concentration	Day 1 of all cycles (each cycle is 21 days)
European Organization for Research and Treatment of Cancer Quality-of-Life-Questionnaire-Core-30 (EORTC QLQ-C30) scores	Patient-reported outcomes including health-related quality of life, pain, and overall change in participant's health will be assessed using the EORTC QLQ-C30. The EORTC QLQ-C30 includes 30 items resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 Global Health Status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Scores are transformed to a 0 to 100 scale. Higher scores indicated worse outcome.	Baseline to End of Study (approximately 3 years)
EuroQol-EQ-5D (EQ-5D-5L) questionnaire scores	EQ-5D-5L is a 5 item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).	Baseline to End of Study (approximately 3 years)

Collaborators and Investigators

• Sponsor: Geron Corporation
• Investigators: Study Director: Faye Feller, Geron Corporation

Publications and helpful links

General Publications

• Mascarenhas J, Harrison CN, Kiladjian JJ, Komrokji RS, Koschmieder S, Vannucchi AM, Berry T, Redding D, Sherman L, Dougherty S, Peng L, Sun L, Huang F, Wan Y, Feller FM, Rizo A, Verstovsek S. Imetelstat in intermediate-2 or high-risk myelofibrosis refractory to JAK inhibitor: IMpactMF phase III study design. Future Oncol. 2022 Jul;18(22):2393-2402. doi: 10.2217/fon-2022-0235. Epub 2022 May 5.

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2021
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: September 18, 2020
• First Submitted That Met QC Criteria: October 2, 2020
• First Posted (Actual): October 6, 2020

Study Record Updates

• Last Update Posted (Estimated): December 4, 2025
• Last Update Submitted That Met QC Criteria: November 26, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Thrombocythemia; Polycythemia; Myeloproliferative neoplasms; Primary myelofibrosis; Janus Kinase-Inhibitor
• Additional Relevant MeSH Terms: Hematologic Diseases; Bone Marrow Diseases; Blood Platelet Disorders; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Thrombocytosis; Polycythemia; Primary Myelofibrosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; imetelstat; GRN163L peptide
• Other Study ID Numbers: MYF3001; 2020-003288-24 (EudraCT Number); 2023-509120-17-00 (Ctis)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No