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
3 other identifiers
interventional
327
25 countries
170
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Apr 2021
Longer than P75 for phase_3
170 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 18, 2020
CompletedFirst Posted
Study publicly available on registry
October 6, 2020
CompletedStudy Start
First participant enrolled
April 12, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 30, 2028
December 4, 2025
October 1, 2025
7.2 years
September 18, 2020
November 26, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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 Outcomes (12)
Symptom response rate
Baseline (Day 1), and at Week 24
Progression-free survival
Baseline (Day 1) until End of Study (EOS) (approximately 3 years)
Spleen response rate
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
Baseline (Day 1) until End of Treatment (approximately 3 years)
Reduction in the degree of bone marrow fibrosis
Baseline (Day 1) until End of Treatment (approximately 3 years)
- +7 more secondary outcomes
Study Arms (2)
Imetelstat
EXPERIMENTALParticipants 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.
Best Available Therapy (BAT)
ACTIVE COMPARATORParticipants 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.
Interventions
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.
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.
Eligibility Criteria
You may qualify if:
- 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
- (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:
- no decrease in spleen volume (\< 10% by MRI or CT) from the start of treatment with JAK-inhibitor
- no decrease in spleen size (\< 30% by palpation or length by imaging) from the start of treatment with JAK-inhibitor
- no decrease in symptoms (\< 20% by Myelofibrosis Symptom Assessment Form \[MFSAF\] or myeloproliferative neoplasm SAF) from the start of treatment with JAK-inhibitor
- a score of at least 15 on TSS assessed using the MFSAF v4.0 during screening.
- (iii) Following maximum tolerated doses of JAK inhibitor therapy for ≥3 months duration, having documented relapsed disease defined as either
- Increase in spleen volume from time of best response by 25% measured by MRI or CT, or
- 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)
- +5 more criteria
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (174)
University of California-San Diego/Moores UCSD Cancer Center
La Jolla, California, 92093-1503, United States
UCLA David Geffen School of Medicine
Los Angeles, California, 90096, United States
Smilow Cancer Center at YNHH
New Haven, Connecticut, 06511, United States
BRCR Medical Center Inc
Plantation, Florida, 33326, United States
University of South Florida
Tampa, Florida, 33612, United States
Norton Cancer Institute
Louisville, Kentucky, 40207, United States
Ochsner Clinic Foundation
New Orleans, Louisiana, 70124, United States
Maryland Oncology Hematology
Rockville, Maryland, 20850, United States
Icahn School of Medicine at Mount Sinai
New York, New York, 10029, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Gabrail Cancer Center
Canton, Ohio, 44718, United States
Prairie Lakes Health Care System, Inc.
Watertown, South Dakota, 57201, United States
Oncology Consultants
Houston, Texas, 77024, United States
The University of Texas MD
Houston, Texas, 77030-4000, United States
Community Cancer Trials of Utah
Ogden, Utah, 84405, United States
Utah Cancer Specialists
Salt Lake City, Utah, 84106, United States
Hematology Oncology Associates of Fredericksburg
Fredericksburg, Virginia, 22408, United States
Northwest Medical Specialties PLLC
Seattle, Washington, 98405, United States
Hospital Aleman
Ciudad de Buenos Aires, Buenos Aires, C118AAT, Argentina
Sanatorio de la Mujer
Rosario, Santa Fe Province, S2000ORE, Argentina
Sanatorio Allende
Córdoba, X5000JHQ, Argentina
Royal North Shore Hospital
St Leonards, New South Wales, 2065, Australia
Royal Brisbane and Women's Hospital
Herston, Queensland, 4011, Australia
Royal Hobart Hospital
Hobart, Tasmania, 7000, Australia
Epworth Healthcare
Richmond, Victoria, 3121, Australia
Krankenhaus Hietzing mit Neurologischem Zentrum Rosenhügel
Wein, Burgenland, 1130, Austria
Krankenhaus der Elisabethinen
Linz, Upper Austria, 4020, Austria
Kepler Universitätsklinikum Gm
Linz, Upper Austria, 4021, Austria
Klinikum Wels-Grieskirchen GmbH
Wels, Upper Austria, 4600, Austria
AZ Klina
Antwerp, Antwerpen, 2930, Belgium
UZ Antwerpen
Edegem, Antwerpen, 2650, Belgium
Centre Hospitalier de Jolimont
Haine-Saint-Paul, Hainaut, 7100, Belgium
Universitair Ziekenhuis Gent
Ghent, Oost-Vlaanderen, 9000, Belgium
Universitair Ziekenhuis Brussel - Myeloom Centrum Brussel (MCB)
Jette, Belgium
Centro de oncologia Leonardo da Vinci
Fortaleza, Ceará, 60135285, Brazil
Hospital das Clínicas UFG
Goiânia, Goiás, 74605, Brazil
Hospital Erasto Gaertner
Curitiba, Paraná, 81520-060, Brazil
Hospital de Clinicas de Porto Alegre - UFRGS
Porto Alegre, Rio Grande do Sul, 90035-903, Brazil
Centro Gaucho Integrado de Oncologia, Hematologia, Ensino e Pesquisa LTDA
Porto Alegre, Rio Grande do Sul, 90470340, Brazil
Instituto de Educação, Pesquisa e Gestão em Saúde
São Paulo, São Paulo, 01323000, Brazil
Hospital Israelita Albert Einstein
São Paulo, São Paulo, 05651-901, Brazil
Fundacao Doutor Amaral Carvalho / Hospital Amaral Carvalho
São Paulo, São Paulo, 17210-120, Brazil
CEPON Centro de Pesquisas Oncologicas SC
Florianópolis, 88034-000, Brazil
Hospital A.C.Camargo Cancer Center - Clinical Oncology
São Paulo, Brazil
UMBAL Sveti Georgi
Plovdiv, Plovdiv, 4002, Bulgaria
Specialized Hospital for Active Therapy of Hematological dis
Sofia, Sofia, 1756, Bulgaria
Oncologos del Occidente S.A
Pereira, Risaralda Department, 660000, Colombia
Hospital Pablo Tobon Uribe
Antioquia, Colombia
Centro Medico Imbanaco de Cali S.A.
Cali, 760042, Colombia
Odense University Hospital - Hematology
Odense, DK-5000 C, Denmark
Centre Hospitalier Lyon
Pierre-Bénite, Auvergne-Rhône-Alpes, 69495, France
CHU Bretonneau
Tours, Indre-et-Loire, 37044, France
Hopital Bicetre
Paris, Le Kremlin-Bicêtre, 94270, France
CHU De Nantes - Hematologie
Nantes, Loire-Atlantique, 44000, France
CHU de Nice - Hopital de l'Archet II - Pharmacie
Nice, Nice Cedex 3, 06202, France
Hospital CENTRE HOSPITALIER AVIGNON
Avignon, Provence-Alpes-Côte d'Azur Region, 84902, France
Centre Hospitalier Du Mans - Cancérologie Médicale
Le Mans, Sarthe, 72037, France
CHRU Brest - Hôpital Morvan
Brest, 29609, France
CHU - Hôpital Saint Louis - Centre D'Investigations Cliniq
Paris, 75010, France
Hopital Cochin - Aphp Hôpitaux Universitaires Paris Centre
Paris, Île-de-France Region, 75679, France
J.S.C."K.Eristavi National Cen
Tbilisi, K'alak'i T'bilisi, 0159, Georgia
Ltd "Medinvest - Institute of Hematology and Trans
Tbilisi, K'alak'i T'bilisi, 186, Georgia
LTD Israeli-Georgian Medical R
Tbilisi, 0112, Georgia
M.Zodelava Hematology Center L
Tbilisi, 0112, Georgia
Multi Profile Clinic Consilium
Tbilisi, 0179, Georgia
Universitätsklinikum Mannheim - University of Heidelberg
Mannheim, Baden-Wurttemberg, 68167, Germany
Universitätsklinikum Tübingen
Tübingen, Baden-Wurttemberg, 72076, Germany
Universitätsklinikum Carl Gust
Dresden, Hamburg, 1307, Germany
Klinikum Kempten-Oberallgaeu GmbH
Kempten, Rhineland-Palatinate, 87439, Germany
Universitätsklinikum Leipzig AöR
Leipzig, Saxony, 04103, Germany
Martin-Luther-Universität Halle-Wittenberg
Halle, Saxony-Anhalt, 6120, Germany
Szabolcs-Szatmár-Bereg Megyei Önkormányzat Jósa András
Nyíregyháza, 4400, Hungary
Nirmal Hospital - Hematology
Surat, Gujarat, 395002, India
St. John's Medical College Hospital
Bangalore, Karnataka, 560 034, India
Fortis Hospital 154/9
Bengaluru, Karnataka, 560076, India
All India Institute of Medical Sciences, Dept. of Hematology, New Delhi (All India Institute Of Medical Sciences)
New Delhi, National Capital Territory of Delhi, 110029, India
Sir Ganga Ram Hospital
New Delhi, National Capital Territory of Delhi, 110060, India
Fortis Memorial Research Institute
Gūrgaon, New Delhi, 122002, India
All India Institute of Medical Sciences
Bhubaneswar, Odisha, 751019, India
Nilratan Sircar Medical College
Kolkata, West Bengal, 700014, India
Narayana Hrudayalaya Hospital
Hyderabad, 560099, India
Deenanath Mangeshkar Hospital & Research Center
Pune, 411004, India
Sahyadri Specialty Hospital
Pune, India
Kaplan Medical Center
Rehovot, Central District, 7610001, Israel
Shamir Medical Center (Assaf Harofeh)
Ẕerifin, Central District, 7030000, Israel
Hadassah Medical Organization
Jerusalem, Jerusalem, 9112001, Israel
Western Galilee Hospital - Nahariya
Nahariya, Northern District, 22100, Israel
Assuta Ashdod University Hospi
Ashdod, Southern District, 7747629, Israel
Barzilai Medical Center
Ashkelon, Southern District, 78278, Israel
Soroka Medical Center - Hematology Institute
Beersheba, 84101, Israel
Bnai Zion Medical Center
Haifa, 31048, Israel
Carmel MC
Haifa, 3436212, Israel
PO Civile SS.Antonio e Biagio
Alessandria, Alessandria, 15121, Italy
A.O.di Bologna Policl.S.Orsola
Bologna, Bologna, 40138, Italy
Arcispedale S.Anna - Ematologi
Cona, Ferrara, 44124, Italy
AOU Careggi
Florence, Firenze, 50134, Italy
IRCCS Ospedale Policlinico San Martino
Genova, Genova, 16132, Italy
Clinica Ematologica, Univ. Deg
Genova, Genova, 6- 16132, Italy
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Milan, Milano, 20122, Italy
Ospedale Civile S.Maria delle Croci, AUSL Ravenna
Ravenna, Ravenna, 48121, Italy
Arcispedale S Maria Nuova, AO di Reggio Emilia
Reggio Calabria, Reggio Calabria, 42123, Italy
Azienda Ospedaliera Bianchi-Me
Reggio Calabria, Reggio Calabria, 89124, Italy
AUSL di Rimini Ospedale Infermi di Rimini
Rimini, Rimini, 47900, Italy
Policlinico Universitario Agostino Gemelli
Roma, Roma, 00168, Italy
AOU San Luigi Gonzaga
Orbassano, Torino, 10043, Italy
AOU Città della Salute e della Scienza di Torino
Torino, Torino, 10126, Italy
Ospedale di Circolo, PO Varese
Varese, Varese, 21100, Italy
Ospedale S.Bortolo, AULSS n.6
Vicenza, Vicenza, 36100, Italy
Presidio Ospedaliero Garibaldi
Catania, 95122, Italy
Irccs Irst
Meldola, 47014, Italy
Ospedale San Raffaele
Milan, 20132, Italy
ASST Grande Ospedale Metropoli
Milan, 20162, Italy
Azienda Ospedaliera San Gerard
Monza, 20900, Italy
AOU Federico II
Naples, 80122, Italy
ASL Roma 2 - PO "S. Eugenio"
Roma, 00144, Italy
Hospital Pulau Pinang
Pulau Pinang, Georgetown, 10990, Malaysia
Hospital Sultanah Aminah Johor Bahru
Johor Bahru, Johor, 80000, Malaysia
Hospital Raja Perempuan Zainab II
Kota Bharu, Kelantan, 15586, Malaysia
Sarawak General Hospital
Kuching, Sarawak, 93586, Malaysia
Hospital Ampang
Ampang, Selangor, 68000, Malaysia
Ars Medical Sp. z o.o.
Piła, Greater Poland Voivodeship, 64-920, Poland
Centrum Medyczne Pratia Poznan
Skórzewo, Greater Poland Voivodeship, 60-185, Poland
Pratia Onkologia Katowice
Katowice, Silesian Voivodeship, 40-519, Poland
Wojewodzki Szpital Specjalistyczny
Biała Podlaska, 21-500, Poland
CCA-Braga. Centro Clínico Académico - Hospital Braga
Braga, Braga District, 4710-243, Portugal
Centro Clinico Fundacao Champalimaud
Lisbon, Lisbon District, 1400-038, Portugal
H. Santa Maria. Centro Hospita
Lisbon, Lisbon District, 1649-035, Portugal
H. São Francisco Xavier-Centro
Lisbon, 1495-005, Portugal
MONIKI - Oncology
Moscow, Moscow Oblast, 129110, Russia
MUZ City Clinical Hospital # 2
Novosibirsk, Novosibirsk Oblast, 630091, Russia
Budgetary Healthcare Institution of Omsk Region
Omsk, 644013, Russia
GOU VPO Saratov State Medical University n.a. V.I.
Saratov, 410012, Russia
National University Cancer Institute (NCIS)
Singapore, Central Singapore, 119074, Singapore
Singapore General Hospital
Singapore, Central Singapore, 169608, Singapore
Inje University Busan Paik Hos
Busan, Busan Gwang'Yeogsi [Pusan-Kwangyokshi], 47392, South Korea
Inje University Haeundae Paik Hospital
Busan, Busan Gwang'Yeogsi [Pusan-Kwangyokshi], 48108, South Korea
National Cancer Institute Center for Cancer Research
Goyang-si, Gyeonggido, 10408, South Korea
Gachon University Gil Medical Center
Incheon, Incheon Gwang'Yeogsi [Inch'n-Kwangyokshi], 21565, South Korea
Korea University Anam Hospital
Seoul, Seoul Teugbyeolsi [Seoul-T'Ukpyolshi], 02841, South Korea
Gangnam Severance Hospital, Yonsei University Health System
Seoul, Seoul Teugbyeolsi [Seoul-T'Ukpyolshi], 06273, South Korea
Korea University Guro Hospital
Seoul, Seoul Teugbyeolsi [Seoul-T'Ukpyolshi], 08308, South Korea
Samsung Medical Center
Seoul, Seoul Teugbyeolsi [Seoul-T'Ukpyolshi], 6351, South Korea
Seoul National University Hospital - Department of Internal
Seoul, Seoul Teugbyeolsi [Seoul-T'Ukp, 03080, South Korea
Pusan National University Hospital - Hematology and Oncology
Busan, 49241, South Korea
The Catholic University of Korea
Seongdong, 6591, South Korea
Severance Hospital, Yonsei Uni
Seoul, 3722, South Korea
H.G.U. Alicante
Alicante, Alicante, 03010, Spain
Institut Català d'Oncologia-Ho
Badalona, Barcelona, 08916, Spain
C.S. Parc Tauli
Sabadell, Barcelona, 08208, Spain
Hospital Universitario de Gran
Las Palmas de Gran Canaria, Canary Islands, 35019, Spain
H. San Pedro de Alcántara
Cáceres, Cáceres, 10003, Spain
ICO-Hospital Universitari de G
Girona, Girona, 17007, Spain
Hospital Universitario Virgen
Granada, Granada, 18014, Spain
Hospital U. 12 Octubre
Madrid, Madrid, 28041, Spain
H.U. La Paz
Madrid, Madrid, 28046, Spain
H.U.V. de la Victoria
Málaga, Málaga, 29010, Spain
H.U. Ribera de Alzira
Alzira, Valencia, 46600, Spain
H. Quirón Zaragoza
Zaragoza, Zaragoza, 50012, Spain
Hospital Universitario Fundaci
Madrid, 28040, Spain
Hospital Universitario de Salamanco
Salamanca, 37007, Spain
Chang Gung Medical Foundation
Chiayi City, Chiayi, 613, Taiwan
Tri-Service General Hospital
Taipei, Taipei, 11490, Taiwan
China Medical University Hospital - Hematology/Onc
Taichung, 404, Taiwan
Ankara University Medical Facu
Ankara, Ankara, 6590, Turkey (Türkiye)
Istanbul üniversitesi cerrahpaşa
Istanbul, Istanbul, 34098, Turkey (Türkiye)
Medipol Bagcilar Mega Hospital
Istanbul, Istanbul, 34214, Turkey (Türkiye)
Marmara university pendik training and research hospital
Istanbul, Istanbul, 34899, Turkey (Türkiye)
Ege Universitesi Tip Fakultesi
Izmir, İzmir, 35100, Turkey (Türkiye)
Medical Park Mersin Hastanesi
Mersin, Mersin, Turkey (Türkiye)
Sakarya Research and Training Hospital - Medical Oncology
Adapazarı, 54100, Turkey (Türkiye)
Gazi University Medical Faculty
Ankara, 06560, Turkey (Türkiye)
St Bartholomew's Hospital
London, EC1A 7BE, United Kingdom
Guys and St Thomas' Hospital
London, SE1 9RT, United Kingdom
Oxford University Hospitals
Oxford, OX3 9DS, United Kingdom
Related Publications (1)
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.
PMID: 35510486DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Faye Feller
Geron Corporation
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 18, 2020
First Posted
October 6, 2020
Study Start
April 12, 2021
Primary Completion (Estimated)
June 30, 2028
Study Completion (Estimated)
June 30, 2028
Last Updated
December 4, 2025
Record last verified: 2025-10