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

NCT ID: NCT04576156

Last Updated: 2025-12-04

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 327 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-12
• Study Completion Date: 2028-06-30

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.

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.

Conditions

Myelofibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Imetelstat

Intervention Type: DRUG

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.

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.

Group Type: ACTIVE_COMPARATOR

Best Available Therapy (BAT)

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

GRN163L

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Geron Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Faye Feller

Role: STUDY_DIRECTOR

Geron Corporation

Locations

University of California-San Diego/Moores UCSD Cancer Center

La Jolla, California, United States

UCLA David Geffen School of Medicine

Los Angeles, California, United States

Smilow Cancer Center at YNHH

New Haven, Connecticut, United States

BRCR Medical Center Inc

Plantation, Florida, United States

University of South Florida

Tampa, Florida, United States

Norton Cancer Institute

Louisville, Kentucky, United States

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Maryland Oncology Hematology

Rockville, Maryland, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Gabrail Cancer Center

Canton, Ohio, United States

Prairie Lakes Health Care System, Inc.

Watertown, South Dakota, United States

Oncology Consultants

Houston, Texas, United States

The University of Texas MD

Houston, Texas, United States

Community Cancer Trials of Utah

Ogden, Utah, United States

Utah Cancer Specialists

Salt Lake City, Utah, United States

Hematology Oncology Associates of Fredericksburg

Fredericksburg, Virginia, United States

Northwest Medical Specialties PLLC

Seattle, Washington, United States

Hospital Aleman

Ciudad de Buenos Aires, Buenos Aires, Argentina

Sanatorio de la Mujer

Rosario, Santa Fe Province, Argentina

Sanatorio Allende

Córdoba, , Argentina

Royal North Shore Hospital

St Leonards, New South Wales, Australia

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

Royal Hobart Hospital

Hobart, Tasmania, Australia

Epworth Healthcare

Richmond, Victoria, Australia

Krankenhaus Hietzing mit Neurologischem Zentrum Rosenhügel

Wein, Burgenland, Austria

Krankenhaus der Elisabethinen

Linz, Upper Austria, Austria

Kepler Universitätsklinikum Gm

Linz, Upper Austria, Austria

Klinikum Wels-Grieskirchen GmbH

Wels, Upper Austria, Austria

AZ Klina

Antwerp, Antwerpen, Belgium

UZ Antwerpen

Edegem, Antwerpen, Belgium

Centre Hospitalier de Jolimont

Haine-Saint-Paul, Hainaut, Belgium

Universitair Ziekenhuis Gent

Ghent, Oost-Vlaanderen, Belgium

Universitair Ziekenhuis Brussel - Myeloom Centrum Brussel (MCB)

Jette, , Belgium

Centro de oncologia Leonardo da Vinci

Fortaleza, Ceará, Brazil

Hospital das Clínicas UFG

Goiânia, Goiás, Brazil

Hospital Erasto Gaertner

Curitiba, Paraná, Brazil

Hospital de Clinicas de Porto Alegre - UFRGS

Porto Alegre, Rio Grande do Sul, Brazil

Centro Gaucho Integrado de Oncologia, Hematologia, Ensino e Pesquisa LTDA

Porto Alegre, Rio Grande do Sul, Brazil

Instituto de Educação, Pesquisa e Gestão em Saúde

São Paulo, São Paulo, Brazil

Hospital Israelita Albert Einstein

São Paulo, São Paulo, Brazil

Fundacao Doutor Amaral Carvalho / Hospital Amaral Carvalho

São Paulo, São Paulo, Brazil

CEPON Centro de Pesquisas Oncologicas SC

Florianópolis, , Brazil

Hospital A.C.Camargo Cancer Center - Clinical Oncology

São Paulo, , Brazil

UMBAL Sveti Georgi

Plovdiv, Plovdiv, Bulgaria

Specialized Hospital for Active Therapy of Hematological dis

Sofia, Sofia, Bulgaria

Oncologos del Occidente S.A

Pereira, Risaralda Department, Colombia

Hospital Pablo Tobon Uribe

Antioquia, , Colombia

Centro Medico Imbanaco de Cali S.A.

Cali, , Colombia

Odense University Hospital - Hematology

Odense, , Denmark

Centre Hospitalier Lyon

Pierre-Bénite, Auvergne-Rhône-Alpes, France

CHU Bretonneau

Tours, Indre-et-Loire, France

Hopital Bicetre

Paris, Le Kremlin-Bicêtre, France

CHU De Nantes - Hematologie

Nantes, Loire-Atlantique, France

CHU de Nice - Hopital de l'Archet II - Pharmacie

Nice, Nice Cedex 3, France

Hospital CENTRE HOSPITALIER AVIGNON

Avignon, Provence-Alpes-Côte d'Azur Region, France

Centre Hospitalier Du Mans - Cancérologie Médicale

Le Mans, Sarthe, France

CHRU Brest - Hôpital Morvan

Brest, , France

CHU - Hôpital Saint Louis - Centre D'Investigations Cliniq

Paris, , France

Hopital Cochin - Aphp Hôpitaux Universitaires Paris Centre

Paris, Île-de-France Region, France

J.S.C."K.Eristavi National Cen

Tbilisi, K'alak'i T'bilisi, Georgia

Ltd "Medinvest - Institute of Hematology and Trans

Tbilisi, K'alak'i T'bilisi, Georgia

LTD Israeli-Georgian Medical R

Tbilisi, , Georgia

M.Zodelava Hematology Center L

Tbilisi, , Georgia

Multi Profile Clinic Consilium

Tbilisi, , Georgia

Universitätsklinikum Mannheim - University of Heidelberg

Mannheim, Baden-Wurttemberg, Germany

Universitätsklinikum Tübingen

Tübingen, Baden-Wurttemberg, Germany

Universitätsklinikum Carl Gust

Dresden, Hamburg, Germany

Klinikum Kempten-Oberallgaeu GmbH

Kempten, Rhineland-Palatinate, Germany

Universitätsklinikum Leipzig AöR

Leipzig, Saxony, Germany

Martin-Luther-Universität Halle-Wittenberg

Halle, Saxony-Anhalt, Germany

Szabolcs-Szatmár-Bereg Megyei Önkormányzat Jósa András

Nyíregyháza, , Hungary

Nirmal Hospital - Hematology

Surat, Gujarat, India

St. John's Medical College Hospital

Bangalore, Karnataka, India

Fortis Hospital 154/9

Bengaluru, Karnataka, 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, India

Sir Ganga Ram Hospital

New Delhi, National Capital Territory of Delhi, India

Fortis Memorial Research Institute

Gurgaon, New Delhi, India

All India Institute of Medical Sciences

Bhubaneswar, Odisha, India

Nilratan Sircar Medical College

Kolkata, West Bengal, India

Narayana Hrudayalaya Hospital

Hyderabad, , India

Deenanath Mangeshkar Hospital & Research Center

Pune, , India

Sahyadri Specialty Hospital

Pune, , India

Kaplan Medical Center

Rehovot, Central District, Israel

Shamir Medical Center (Assaf Harofeh)

Ẕerifin, Central District, Israel

Hadassah Medical Organization

Jerusalem, Jerusalem, Israel

Western Galilee Hospital - Nahariya

Nahariya, Northern District, Israel

Assuta Ashdod University Hospi

Ashdod, Southern District, Israel

Barzilai Medical Center

Ashkelon, Southern District, Israel

Soroka Medical Center - Hematology Institute

Beersheba, , Israel

Bnai Zion Medical Center

Haifa, , Israel

Carmel MC

Haifa, , Israel

PO Civile SS.Antonio e Biagio

Alessandria, Alessandria, Italy

A.O.di Bologna Policl.S.Orsola

Bologna, Bologna, Italy

Arcispedale S.Anna - Ematologi

Cona, Ferrara, Italy

AOU Careggi

Florence, Firenze, Italy

IRCCS Ospedale Policlinico San Martino

Genova, Genova, Italy

Clinica Ematologica, Univ. Deg

Genova, Genova, Italy

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Milan, Milano, Italy

Ospedale Civile S.Maria delle Croci, AUSL Ravenna

Ravenna, Ravenna, Italy

Arcispedale S Maria Nuova, AO di Reggio Emilia

Reggio Calabria, Reggio Calabria, Italy

Azienda Ospedaliera Bianchi-Me

Reggio Calabria, Reggio Calabria, Italy

AUSL di Rimini Ospedale Infermi di Rimini

Rimini, Rimini, Italy

Policlinico Universitario Agostino Gemelli

Roma, Roma, Italy

AOU San Luigi Gonzaga

Orbassano, Torino, Italy

AOU Città della Salute e della Scienza di Torino

Torino, Torino, Italy

Ospedale di Circolo, PO Varese

Varese, Varese, Italy

Ospedale S.Bortolo, AULSS n.6

Vicenza, Vicenza, Italy

Presidio Ospedaliero Garibaldi

Catania, , Italy

Irccs Irst

Meldola, , Italy

Ospedale San Raffaele

Milan, , Italy

ASST Grande Ospedale Metropoli

Milan, , Italy

Azienda Ospedaliera San Gerard

Monza, , Italy

AOU Federico II

Napoli, , Italy

ASL Roma 2 - PO "S. Eugenio"

Roma, , Italy

Hospital Pulau Pinang

Pulau Pinang, Georgetown, Malaysia

Hospital Sultanah Aminah Johor Bahru

Johor Bahru, Johor, Malaysia

Hospital Raja Perempuan Zainab II

Kota Bharu, Kelantan, Malaysia

Sarawak General Hospital

Kuching, Sarawak, Malaysia

Hospital Ampang

Ampang, Selangor, Malaysia

Ars Medical Sp. z o.o.

Piła, Greater Poland Voivodeship, Poland

Centrum Medyczne Pratia Poznan

Skórzewo, Greater Poland Voivodeship, Poland

Pratia Onkologia Katowice

Katowice, Silesian Voivodeship, Poland

Wojewodzki Szpital Specjalistyczny

Biała Podlaska, , Poland

CCA-Braga. Centro Clínico Académico - Hospital Braga

Braga, Braga District, Portugal

Centro Clinico Fundacao Champalimaud

Lisbon, Lisbon District, Portugal

H. Santa Maria. Centro Hospita

Lisbon, Lisbon District, Portugal

H. São Francisco Xavier-Centro

Lisbon, , Portugal

MONIKI - Oncology

Moscow, Moscow Oblast, Russia

MUZ City Clinical Hospital # 2

Novosibirsk, Novosibirsk Oblast, Russia

Budgetary Healthcare Institution of Omsk Region

Omsk, , Russia

GOU VPO Saratov State Medical University n.a. V.I.

Saratov, , Russia

National University Cancer Institute (NCIS)

Singapore, Central Singapore, Singapore

Singapore General Hospital

Singapore, Central Singapore, Singapore

Inje University Busan Paik Hos

Busan, Busan Gwang'Yeogsi [Pusan-Kwangyokshi], South Korea

Inje University Haeundae Paik Hospital

Busan, Busan Gwang'Yeogsi [Pusan-Kwangyokshi], South Korea

National Cancer Institute Center for Cancer Research

Goyang-si, Gyeonggido, South Korea

Gachon University Gil Medical Center

Incheon, Incheon Gwang'Yeogsi [Inch'n-Kwangyokshi], South Korea

Korea University Anam Hospital

Seoul, Seoul Teugbyeolsi [Seoul-T'Ukpyolshi], South Korea

Gangnam Severance Hospital, Yonsei University Health System

Seoul, Seoul Teugbyeolsi [Seoul-T'Ukpyolshi], South Korea

Korea University Guro Hospital

Seoul, Seoul Teugbyeolsi [Seoul-T'Ukpyolshi], South Korea

Samsung Medical Center

Seoul, Seoul Teugbyeolsi [Seoul-T'Ukpyolshi], South Korea

Seoul National University Hospital - Department of Internal

Seoul, Seoul Teugbyeolsi [Seoul-T'Ukp, South Korea

Pusan National University Hospital - Hematology and Oncology

Busan, , South Korea

The Catholic University of Korea

Seongdong, , South Korea

Severance Hospital, Yonsei Uni

Seoul, , South Korea

H.G.U. Alicante

Alicante, Alicante, Spain

Institut Català d'Oncologia-Ho

Badalona, Barcelona, Spain

C.S. Parc Tauli

Sabadell, Barcelona, Spain

Hospital Universitario de Gran

Las Palmas de Gran Canaria, Canary Islands, Spain

H. San Pedro de Alcántara

Cáceres, Cáceres, Spain

ICO-Hospital Universitari de G

Girona, Girona, Spain

Hospital Universitario Virgen

Granada, Granada, Spain

Hospital U. 12 Octubre

Madrid, Madrid, Spain

H.U. La Paz

Madrid, Madrid, Spain

H.U.V. de la Victoria

Málaga, Málaga, Spain

H.U. Ribera de Alzira

Alzira, Valencia, Spain

H. Quirón Zaragoza

Zaragoza, Zaragoza, Spain

Hospital Universitario Fundaci

Madrid, , Spain

Hospital Universitario de Salamanco

Salamanca, , Spain

Chang Gung Medical Foundation

Chiayi City, Chiayi, Taiwan

Tri-Service General Hospital

Taipei, Taipei, Taiwan

China Medical University Hospital - Hematology/Onc

Taichung, , Taiwan

Ankara University Medical Facu

Ankara, Ankara, Turkey (Türkiye)

Istanbul üniversitesi cerrahpaşa

Istanbul, Istanbul, Turkey (Türkiye)

Medipol Bagcilar Mega Hospital

Istanbul, Istanbul, Turkey (Türkiye)

Marmara university pendik training and research hospital

Istanbul, Istanbul, Turkey (Türkiye)

Ege Universitesi Tip Fakultesi

Izmir, İzmir, Turkey (Türkiye)

Medical Park Mersin Hastanesi

Mersin, Mersin, Turkey (Türkiye)

Sakarya Research and Training Hospital - Medical Oncology

Adapazarı, , Turkey (Türkiye)

Gazi University Medical Faculty

Ankara, , Turkey (Türkiye)

St Bartholomew's Hospital

London, , United Kingdom

Guys and St Thomas' Hospital

London, , United Kingdom

Oxford University Hospitals

Oxford, , United Kingdom

Countries

United States; Argentina; Australia; Austria; Belgium; Brazil; Bulgaria; Colombia; Denmark; France; Georgia; Germany; Hungary; India; Israel; Italy; Malaysia; Poland; Portugal; Russia; Singapore; South Korea; Spain; Taiwan; Turkey (Türkiye); United Kingdom

References

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.

Reference Type: DERIVED

PMID: 35510486 (View on PubMed)

Other Identifiers

2020-003288-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-509120-17-00

Identifier Type: CTIS

Identifier Source: secondary_id

MYF3001

Identifier Type: -

Identifier Source: org_study_id