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
Myelofibrosis
About this trial
This is an interventional treatment trial for Myelofibrosis focused on measuring Myeloproliferative neoplasms, Polycythemia, Thrombocythemia, Primary myelofibrosis, Janus Kinase-Inhibitor
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:
- 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.
- (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
- 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)
- 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
Sites / Locations
- Highlands Oncology
- University of California-San Diego/Moores UCSD Cancer CenterRecruiting
- Memorial Care
- UCLA david geffen school of medicineRecruiting
- Sharp HealthCare
- The Oncology Institute - Innovative Clinical Research Institute (ICRI)
- Hartford Healthcare
- Smilow Cancer Center at YNHH
- BRCR Medical Center IncRecruiting
- University of South FloridaRecruiting
- Fort Wayne Medical Oncology and Hematology
- Goshen Center for Cancer Care
- Beacon Health System
- Maryland Oncology Hematology
- Oncology Hematology Associates
- Nebraska Cancer Specialists
- Hematology-Oncology Associates of Central New York (HOACNY)
- Icahn School of Medicine at Mount SinaiRecruiting
- Duke University Medical CenterRecruiting
- Aultman Medical Group
- Gabrail Cancer CenterRecruiting
- Ohio Health
- Cancer Care Associates of York
- Bon Secours (Greenville) - St. Francis Cancer Center
- Sanford Health
- Prairie Lakes Health Care System, Inc.Recruiting
- The University of Texas MDRecruiting
- Oncology Consultants
- Community Cancer Trials of Utah
- Utah Cancer Specialists
- Northwest Medical Specialties PLLCRecruiting
- Northwest Medical Specialties
- Hospital AlemanRecruiting
- Clínica Los Arroyos
- Sanatorio de la MujerRecruiting
- Sanatorio AllendeRecruiting
- Royal North Shore HospitalRecruiting
- Royal Brisbane and Women's HospitalRecruiting
- Royal Hobart HospitalRecruiting
- Epworth HealthcareRecruiting
- Krankenhaus Hietzing mit Neurologischem Zentrum Rosenhügel
- Krankenhaus der ElisabethinenRecruiting
- Kepler Universitätsklinikum GmRecruiting
- Klinikum Wels-Grieskirchen GmbHRecruiting
- UZ AntwerpenRecruiting
- Centre Hospitalier de JolimontRecruiting
- CHU De Liège
- Universitair Ziekenhuis GentRecruiting
- Zna - Campus Middelheim
- ZNA Stuyvenberg Antwerpen
- AZ KlinaRecruiting
- Universitair Ziekenhuis Brussel - Myeloom Centrum Brussel (MCB)Recruiting
- Centro de oncologia Leonardo da VinciRecruiting
- Hospital das Clínicas UFGRecruiting
- Hospital Erasto GaertnerRecruiting
- Hospital de Clinicas de Porto Alegre - UFRGSRecruiting
- Centro Gaucho Integrado de Oncologia, Hematologia, Ensino e Pesquisa LTDARecruiting
- CEPON Centro de Pesquisas Oncologicas SCRecruiting
- Instituto de Educação, Pesquisa e Gestão em SaúdeRecruiting
- Hospital Israelita Albert EinsteinRecruiting
- Fundacao Doutor Amaral Carvalho / Hospital Amaral Carvalho
- Hospital A.C.Camargo Cancer Center - Clinical OncologyRecruiting
- UMHAT "Dr. Georgi Stranski"Recruiting
- UMBAL Sveti GeorgiRecruiting
- Specialized Hospital for Active Therapy of Hematological disRecruiting
- Oncologos del Occidente S.ARecruiting
- Hospital Pablo Tobon UribeRecruiting
- Centro Medico Imbanaco de Cali S.A.Recruiting
- FOSCALRecruiting
- Odense University Hospital - HematologyRecruiting
- Institut de cancérologie du Gard - Hematologie cliniqueRecruiting
- CHU BretonneauRecruiting
- Hopital BicetreRecruiting
- CHU de Limoges DupuytrenRecruiting
- CHU De Nantes - Hématologie CRecruiting
- CHU de Nice - Hopital de l'Archet II - Pharmacie
- Hospital CENTRE HOSPITALIER AVIGNONRecruiting
- Centre Hospitalier LyonRecruiting
- CHU de Saint Etienne
- Centre Hospitalier Du Mans - Cancérologie MédicaleRecruiting
- Hopital Avicenne - Hématologie CliniqueRecruiting
- CHRU Brest - Hôpital MorvanRecruiting
- CHU - Hôpital Saint Louis - Centre D'Investigations CliniqRecruiting
- Hopital Cochin - Aphp Hôpitaux Universitaires Paris CentreRecruiting
- LTD Israeli-Georgian Medical RRecruiting
- M.Zodelava Hematology Center LRecruiting
- J.S.C."K.Eristavi National CenRecruiting
- Multi Profile Clinic ConsiliumRecruiting
- Ltd "Medinvest" Institute of HRecruiting
- Universitätsklinikum Mannheim - University of Heidelberg
- Universitätsklinikum TübingenRecruiting
- Universitätsklinikum Carl GustRecruiting
- Klinikum Kempten-Oberallgaeu GmbHRecruiting
- Martin-Luther-Universität Halle-WittenbergRecruiting
- Universitätsklinikum Leipzig AöRRecruiting
- Universitätsklinikum Schleswig
- Semmelweis Egyetem - III. sz.Recruiting
- Dél-pesti Centrumkórház OrszágRecruiting
- Szabolcs-Szatmár-Bereg Megyei Önkormányzat Jósa AndrásRecruiting
- Fejer Megyei Szent Gyorgy EgyeRecruiting
- All India Institute of Medical Sciences, Dept. of Hematology, New Delhi (All India Institute Of Medical Sciences)
- Sir Ganga Ram HospitalRecruiting
- Nirmal Hospital - HematologyRecruiting
- St. John's Medical College HospitalRecruiting
- Fortis Hospital 154/9Recruiting
- Fortis Memorial Research InstituteRecruiting
- All India Institute of Medical SciencesRecruiting
- Nilratan Sircar Medical College
- Narayana Hrudayalaya HospitalRecruiting
- Deenanath Mangeshkar Hospital & Research CenterRecruiting
- Sahyadri Specialty HospitalRecruiting
- Assuta Ashdod University HospiRecruiting
- Barzilai Medical CenterRecruiting
- Kaplan Medical CenterRecruiting
- Shamir Medical Center (Assaf Harofeh)Recruiting
- Western Galilee Hospital - NahariyaRecruiting
- Tel Aviv Sourasky Medical CentRecruiting
- Hadassah Medical OrganizationRecruiting
- Soroka Medical Center - Hematology Institute
- Bnai Zion Medical CenterRecruiting
- Carmel MCRecruiting
- Arcispedale S.Anna - EmatologiRecruiting
- Istituto Clinico Humanitas RozRecruiting
- AOU San Luigi Gonzaga
- PO Civile SS.Antonio e BiagioRecruiting
- A.O.di Bologna Policl.S.OrsolaRecruiting
- Presidio Ospedaliero GaribaldiRecruiting
- AOU CareggiRecruiting
- IRCCS Ospedale Policlinico San Martino
- Clinica Ematologica, Univ. DegRecruiting
- Irccs IrstRecruiting
- Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
- Ospedale San RaffaeleRecruiting
- ASST Grande Ospedale MetropoliRecruiting
- Azienda Ospedaliera San GerardRecruiting
- AOU Federico IIRecruiting
- Ospedale Civile S.Maria delleRecruiting
- Arcispedale S Maria Nuova, AO di Reggio EmiliaRecruiting
- Azienda Ospedaliera Bianchi-MeRecruiting
- AUSL di Rimini Ospedale InfermRecruiting
- ASL Roma 2 - PO "S. Eugenio"Recruiting
- Policlinico Universitario Agostino GemelliRecruiting
- AOU Città della Salute e della Scienza di Torino
- Ospedale di Circolo, PO Varese
- Ospedale S.Bortolo, AULSS n.6Recruiting
- Inje University Busan Paik HosRecruiting
- Inje University Haeundae Paik Hospital
- Kyungpook National University
- National Cancer Institute Center for Cancer Research
- Gachon University Gil Medical Center
- Korea University Anam Hospital
- Gangnam Severance Hospital, Yonsei University Health SystemRecruiting
- Korea University Guro Hospital
- Samsung Medical Center
- Seoul National University Hospital - Department of InternalRecruiting
- Pusan National University Hospital - Hematology and OncologyRecruiting
- The Catholic University of KoreaRecruiting
- Severance Hospital, Yonsei UniRecruiting
- Hospital Pulau PinangRecruiting
- Hospital Sultanah Aminah Johor Bahru
- Hospital Raja Perempuan Zainab IIRecruiting
- Sarawak General HospitalRecruiting
- Hospital AmpangRecruiting
- Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w SlRecruiting
- Ars Medical Sp. z o.o.Recruiting
- Centrum Medyczne Pratia PoznanRecruiting
- Wojewodzki Szpital Specjalistyczny
- Pratia Onkologia KatowiceRecruiting
- CCA-Braga. Centro Clínico Académico - Hospital BragaRecruiting
- CHUC - Centro Hospitalar e UniRecruiting
- Instituto Português de Oncologia de LisboaRecruiting
- Centro Clinico Fundacao ChampalimaudRecruiting
- H. São Francisco Xavier-CentroRecruiting
- H. Santa Maria. Centro HospitaRecruiting
- MONIKI - OncologyRecruiting
- Moscow City Hospital n.a. Botkin
- Novosibirsk State Medical UnivRecruiting
- GOU VPO Saratov State Medical University n.a. V.I. RazumovskRecruiting
- Tula Regional Clinical Hospital
- Clinical oncological dispensarRecruiting
- Saint-Petersburg State MedicalRecruiting
- V.A. Almazov National MedicalRecruiting
- National University Cancer Institute (NCIS)Recruiting
- Singapore General HospitalRecruiting
- Institut Català d'Oncologia-HoRecruiting
- C.S. Parc TauliRecruiting
- Hospital Universitario de GranRecruiting
- H. Comarcal Costa del Sol
- H.U. Ribera de AlziraRecruiting
- H.G.U. AlicanteRecruiting
- H. San Pedro de AlcántaraRecruiting
- ICO-Hospital Universitari de GRecruiting
- Hospital Universitario VirgenRecruiting
- Hospital Universitario FundaciRecruiting
- Hospital U. 12 OctubreRecruiting
- H.U. La PazRecruiting
- H.U.V. de la Victoria
- Complejo Asistencial UniversitRecruiting
- Hospital Universitario DoctorRecruiting
- H. Quirón ZaragozaRecruiting
- Chang Gung Medical FoundationRecruiting
- China Medical University Hospital - Hematology/OncRecruiting
- Taipei Veterans General Hospital
- Tri-Service General HospitalRecruiting
- Sakarya Research and Training Hospital - Medical Oncology
- Gazi University Medical Faculty
- Ankara University Medical FacuRecruiting
- Istanbul Üniversitesi CerrahpaşaRecruiting
- Medipol Bagcilar Mega Hospital
- Marmara university pendik training and research hospitalRecruiting
- Ege Universitesi Tip FakultesiRecruiting
- Mersin University Medical Faculty
- Maidstone HospitalRecruiting
- St Bartholomew's HospitalRecruiting
- Guys and St Thomas' HospitalRecruiting
- Oxford University HospitalsRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Imetelstat
Best Available Therapy (BAT)
Participants will receive imetelstat at 9.4 mg/kg intravenous (IV) every 21 days (±3 days), until disease progression or unacceptable toxicity, treatment discontinuation or study end.
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.