Myeloproliferative Neoplasms Clinical Trial
A Study of Momelotinib Versus Danazol in Symptomatic and Anemic Myelofibrosis Participants (MOMENTUM)
MOMENTUM is a randomized, double-blind, active control Phase 3 trial intended to confirm the differentiated clinical benefits of the investigational drug momelotinib (MMB) versus danazol (DAN) in symptomatic and anemic subjects who have previously received an approved Janus kinase inhibitor (JAKi) therapy for myelofibrosis (MF). The purpose of this clinical study is to compare the effectiveness and safety of MMB to DAN in treating and reducing: 1) disease related symptoms, 2) the need for blood transfusions and 3) splenomegaly, in adults with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The study is planned in countries including, but not limited to: Australia, Austria, Belgium, Bulgaria, Canada, Czech Republic, Denmark, France, Germany, Hungary, Israel, Italy, New Zealand, Poland, Romania, Singapore, South Korea, Spain, Sweden, Taiwan, UK, and US.
Subjects must be symptomatic with a MFSAF v4.0 Total Symptom Score of â‰¥ 10 at screening, and be anemic with Hgb < 10 g/dL. For subjects with ongoing JAKi therapy at screening, JAKi therapy must be tapered over a period of at least 1 week, followed by a 2-week non-treatment washout interval prior to randomization.
Subjects will be randomized 2:1 to orally self-administer blinded treatment: MMB plus placebo or DAN plus placebo. Subjects randomized to receive MMB who complete the randomized treatment period to the end of Week 24 may continue to receive MMB in the open-label extended treatment period to the end of Week 204 (a total period of treatment of approximately 4 years) if the subject tolerates and continues to benefit from MMB.
Subjects randomized to receive DAN may cross-over to MMB open-label treatment in the following circumstances:
at the end of Week 24 if they complete the randomized treatment period; or
at the end of Week 24 if they discontinue treatment with DAN but continue study assessments and do not receive prohibited medications including alternative active anti-MF therapy; or
at any time during the randomized treatment period if they meet the protocol-defined criteria for radiographically-confirmed symptomatic splenic progression.
Subjects randomized to receive DAN who are receiving clinical benefit at the end of Week 24 may choose to continue DAN therapy up to Week 48. The comparator treatment, DAN, is an approved medication in the US and in some other countries and is recommended by national guidelines as a treatment for anemia in MF.
Age >= 18 years.
Confirmed diagnosis of PMF in accordance with the World Health Organization (WHO) 2016 criteria, or Post- polycythemia vera/essential thrombocythemia (PV/ET) MF in accordance with the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT criteria).
Symptomatic, defined as a TSS of >= 10 units assessed by a single MFSAF v4.0 assessment during Screening prior to Baseline period (Day BL1).
Anemic, defined as a Hgb < 10 g/dL in Screening/Baseline period.
Previously treated with an approved JAK inhibitor for PMF or Post-PV/ET MF for >= 90 days, or >= 28 days if JAK inhibitor therapy is complicated by RBC transfusion requirement of >= 4 units in 8 weeks, or Grade 3/4 AEs of thrombocytopenia, anemia, or hematoma.
Baseline splenomegaly, defined as having a palpable spleen at >= 5 centimeter (cm), below the left costal margin, or with volume >= 450 cubic centimeter (cm^3) on imaging (ultrasound, magnetic resonance imaging [MRI] or computed tomography [CT] are acceptable), assessed during Screening at any point prior to Randomization.
High risk, intermediate-2, or intermediate-1 risk MF as defined by Dynamic International Prognostic Scoring System (DIPSS), or DIPSS-plus.
No allogeneic stem cell transplant planned.
Acceptable laboratory assessments:
Absolute neutrophil count (ANC) >= 0.75 × 10^9/Liter (L).
Platelet count (PLT) >= 25 × 10^9/L (without requirement for platelet transfusion).
Peripheral blast count < 10%.
Alanine aminotransferase/ glutamic-oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/ serum glutamic-pyruvic transaminase (ALT/SGPT) <= 3 × Upper Limit Normal (ULN) (<= 5 × ULN if liver is involved by extramedullary hematopoiesis as judged by the investigator or if related to iron chelator therapy that was started within the prior 60 days).
Calculated creatinine clearance (CCr) >= 30 milliliter per minute (mL/min) according to Cockcroft-Gault.
Direct bilirubin <= 2.0 × ULN.
Use of the following treatments within the time periods noted:
Prior momelotinib treatment at any time.
Approved JAK inhibitor therapy (eg, fedratinib or ruxolitinib) within 1 week prior to the first day of Baseline.
Active anti-MF therapy within 1 week prior to the first day of Baseline.
Potent Cytochrome P450 3A4 (CYP3A4) inducers within 1 week prior to Randomization.
Investigational agent (including investigational JAK inhibitors) within 4 weeks prior to Randomization.
Erythropoiesis stimulating agent (ESA) within 4 weeks prior to Randomization.
Danazol within 3 months prior to Randomization.
Splenic irradiation within 3 months prior to Randomization.
Current treatment with simvastatin, atorvastatin, lovastatin or rosuvastatin.
History of prostate cancer, with the exception of localized prostate cancer that has been treated surgically or by radiotherapy with curative intent and presumed cured.
Prostate specific antigen (PSA) > 4 nanograms per milliliter (ng/mL).
Unsuitable for spleen volume measurements due to prior splenectomy or unwilling or unable to undergo an MRI scan or CT scan for spleen volume measurement per protocol requirements.
Any of the following (criteria a - k):
Uncontrolled intercurrent illness including, but not limited to: active uncontrolled infection (participants receiving outpatient antibacterial and/or antiviral treatments for infection that is under control or as infection prophylaxis may be included in the trial).
Significant active or chronic bleeding event >= Grade 2 per Common Terminology Criteria for Adverse Events (CTCAE) v5.0, within 4 weeks prior to Randomization.
Unstable angina pectoris within 6 months prior to Randomization.
Symptomatic congestive heart failure within 6 months prior to Randomization.
Uncontrolled cardiac arrhythmia within 6 months prior to Randomization.
QT Interval Corrected Using Fridericia's Formula (QTcF) interval > 500 millisecond (msec), unless attributed to bundle branch block.
Current progressive thrombosis despite treatment.
History of porphyria.
Child-Pugh score >= 10.
Psychiatric illness, social situation, or any other condition that would limit compliance with trial requirements or may interfere with the interpretation of study results, as judged by investigator or sponsor.
Inability or unwillingness to comply with the protocol restrictions on MF therapy and other medications prior to and during study treatment.
Participants with a prior or concurrent malignancy, whose natural history or treatment has a significant potential to interfere with the safety or efficacy assessment of the investigational regimen.
Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding or thalassemia.
Known positive status for human immunodeficiency viruses (HIV).
Chronic active or acute viral hepatitis A, B, or C infection, or hepatitis B or C carrier (testing required for hepatitis B and C).
Unresolved non-hematologic toxicities from prior therapies that are > Grade 1 per CTCAE v5.0.
Presence of peripheral neuropathy >= Grade 2 per CTCAE v5.0.
Women who are already pregnant or lactating. Additional inclusion/exclusion criteria may apply.
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There are 159 Locations for this study
Phoenix Arizona, 85054, United States
Irvine California, 92614, United States
Los Angeles California, 91011, United States
Whittier California, 90603, United States
Aurora Colorado, 80045, United States
Washington District of Columbia, 20057, United States
Tampa Florida, 33612, United States
Rolling Meadows Illinois, 60008, United States
Saint Louis Missouri, 63110, United States
Hackensack New Jersey, 07601, United States
New York New York, 10032, United States
Avon Ohio, 44011, United States
Canton Ohio, 44718, United States
Cleveland Ohio, 44106, United States
Pittsburgh Pennsylvania, 15224, United States
Houston Texas, 77030, United States
San Antonio Texas, 78229, United States
Garran Australian Capital Territory, 2605, Australia
Waratah New South Wales, 2298, Australia
Bedford Park South Australia, 5042, Australia
Melbourne Victoria, 3004, Australia
Perth Western Australia, 6000, Australia
Innsbruck Tyrol, 6020, Austria
Linz Upper Austria, 4020, Austria
Wien Vienna, 1090, Austria
Steyr , 4400, Austria
Bruxelles Brussels, 1070, Belgium
Charleroi Hainaut, 6000, Belgium
Brugge West-Vlaanderen, 8000, Belgium
Antwerpen , 2060, Belgium
Liège , B-400, Belgium
Pleven , 5800, Bulgaria
Sofia , 1431, Bulgaria
Sofia , 1431, Bulgaria
Sofia , 1756, Bulgaria
Vancouver British Columbia, V6Z 1, Canada
Halifax Nova Scotia, B3H 1, Canada
Hamilton Ontario, L8V 5, Canada
Toronto Ontario, M5G 2, Canada
Montréal Quebec, H3H 2, Canada
Québec , G1J 1, Canada
Brno Jihormoravsky Kraj, 625 0, Czechia
Herlev Hovedstaden, 2730, Denmark
Aalborg Nordjylland, 9000, Denmark
Roskilde Sjælland, 4000, Denmark
Odense Syddanmark, 5000, Denmark
Pessac Aquitaine, 33604, France
Caen Basse-Normandie, 14033, France
Lille Hauts-de-France, 59037, France
Paris Ile-de-France, 75010, France
Paris Ile-de-France, 75571, France
Limoges Limousin, 87042, France
Lens Nord Pas-Des-Calais, 62307, France
Le Mans Pays De La Loire, 72037, France
Amiens Picardie, 80054, France
Nice Provence-Alpes-Côte d'Azur, 06200, France
Pierre-Bénite Rhone-Alps, 69495, France
Angers , 49 93, France
Lille , 59000, France
Marseille , 13385, France
Mulhouse , 68100, France
Nantes , 44000, France
Poitiers , 86021, France
Aachen Nordrhein-Westfalen, 52074, Germany
Essen Nordrhein-Westfalen, 45147, Germany
Minden Nordrhein-Westfalen, 32429, Germany
Halle Sachsen-Anhalt, 06120, Germany
Dresden Sachsen, 01307, Germany
Leipzig Sachsen, 04103, Germany
Jena Thuringen, 07747, Germany
Köln , 50937, Germany
Lübeck , 23538, Germany
Mutlangen , 73557, Germany
Pécs Baranya, 7624, Hungary
Debrecen Hajdu-Bihar, 4032, Hungary
Tatabánya Komárom-Esztergom, 2800, Hungary
Budapest Pest, 1097, Hungary
Kaposvár Somogy, 7400, Hungary
Nyíregyháza Szabolcs-Szatmár-Bereg, 4400, Hungary
Szombathely Vas, 9700, Hungary
Budapest , 1083, Hungary
Győr , 9023, Hungary
Be'er Ya'aqov Central District, 70300, Israel
Haifa Haifa District, 31048, Israel
Jerusalem Jerusalem District, , Israel
Haifa , 31096, Israel
Haifa , 34362, Israel
Jerusalem , 91031, Israel
Kfar Saba , 44281, Israel
Nahariya , , Israel
Petah tikva , 49414, Israel
Tel Aviv , , Israel
Firenze Florence, 50134, Italy
San Giovanni Rotondo Foggia, 71013, Italy
Meldola Forli-Cesena, 47014, Italy
Monza Monza E Brianza, 20900, Italy
Pesaro Pesaro E Urbino, 61121, Italy
Rionero In Vulture Potenza, 85028, Italy
Torino Turin, 10126, Italy
Torino Turin, 10128, Italy
Alessandria , 15121, Italy
Bologna , 40138, Italy
Genova , 16132, Italy
Milano , 20122, Italy
Milano , 20162, Italy
Napoli , 80131, Italy
Novara , 28100, Italy
Roma , 00161, Italy
Roma , 20123, Italy
Udine , 33100, Italy
Varese , 21100, Italy
Verona , 37134, Italy
Daegu Daegu Gwang'yeogsi, 41944, Korea, Republic of
Busan , 47392, Korea, Republic of
Busan , 48108, Korea, Republic of
Seongnam-si , 13620, Korea, Republic of
Seoul , 03722, Korea, Republic of
Seoul , 06591, Korea, Republic of
Seoul , , Korea, Republic of
Seoul , , Korea, Republic of
Ulsan , 44033, Korea, Republic of
Auckland , 0622, New Zealand
Auckland , 2025, New Zealand
Wrocław Dolnoslaskie, 50-36, Poland
Lublin Lubelskie, 20-08, Poland
Kraków Malopolskie, 31-50, Poland
Warszawa Mazowieckie, 02-77, Poland
Warszawa Mazowieckie, 03-40, Poland
Kraków Małopolskie, 31-82, Poland
Opole Opolskie, 45-06, Poland
Gdańsk Pomorskie, 80-21, Poland
Chorzów Salskie, 41-50, Poland
Łódź , 93-51, Poland
Craiova Dolj, 20014, Romania
Iaşi Iasi County, 70048, Romania
Târgu-Mureş Mureș, 54013, Romania
Braşov , 50036, Romania
Bucharest , 030 1, Romania
Singapore , 16960, Singapore
Singapore , 30843, Singapore
Oviedo Asturias, 33011, Spain
Barcelona , 08003, Spain
Barcelona , 08035, Spain
Barcelona , 08916, Spain
Cáceres , 10003, Spain
Girona , 17007, Spain
Madrid , 28034, Spain
Madrid , 28041, Spain
Málaga , 29010, Spain
Salamanca , 37007, Spain
Sevilla , 41013, Spain
Valencia , 46009, Spain
Zaragoza , 50012, Spain
Solna Stockholm, 171 7, Sweden
Göteborg Västra Götalands Län, 413 4, Sweden
Uddevalla , 45153, Sweden
Puzi City Chaiyi, 613, Taiwan
Taichung City Taichung, 40447, Taiwan
Taipei , 10002, Taiwan
Taoyuan , 333, Taiwan
Boston England, PE21 , United Kingdom
Bristol England, BS2 8, United Kingdom
London England, NW1 2, United Kingdom
London England, SE1 9, United Kingdom
London England, W12 0, United Kingdom
Southampton England, SO16 , United Kingdom
Airdrie Scotland, ML6 0, United Kingdom
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