Myeloproliferative Neoplasms Clinical Trial
Study of Oral Navitoclax Tablet in Combination With Oral Ruxolitinib Tablet to Assess Change in Spleen Volume in Adult Participants With Relapsed/Refractory Myelofibrosis
Summary
Myelofibrosis (MF) is a bone marrow illness that affects blood-forming tissues in the body. MF disturbs the body's normal production of blood cells, causing extensive scarring in the bone marrow. This leads to severe anemia, weakness, fatigue, and an enlarged spleen. The purpose of this study is to assess safety and change in spleen volume when navitoclax is given in combination with ruxolitinib, as compared to best available therapy, for adult participants with MF.
Navitoclax is an investigational drug (not yet approved) being developed for the treatment of MF. The study has 2 arms - A and B. In Arm A, participants will receive navitoclax in combination with ruxolitinib. In Arm B, participants will receive the best available therapy (BAT) for MF. Adult participants with a diagnosis of relapsed/refractory (R/R) MF will be enrolled. Approximately 330 participants will be enrolled in approximately 210 sites across the world.
In Arm A, participants will receive oral navitoclax tablet once daily with oral ruxolitinib tablet twice daily. In Arm B, participants will receive the BAT as identified by the investigator. Treatment will continue until clinical benefit is not seen, participants cannot tolerate the study drugs, or participants withdraw consent. The approximate treatment duration is about 3 years.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of treatment will be checked by medical assessments, blood and bone marrow tests, checking for side effects, and completing questionnaires.
Eligibility Criteria
Inclusion Criteria:
Must complete the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 on at least 4 out of the 7 days immediately prior to the date of randomization and must agree to collect MFSAF data daily by ePRO device during the study collection window.
-- Has at least 2 symptoms each with an average score >= 3 or an average total score of >= 12, as measured by the MFSAF v4.0.
Documented diagnosis of primary myelofibrosis (MF) as defined by the World Health Organization (WHO) classification, post polycythemia vera (PPV)-MF, or post essential thrombocytopenia (PET)-MF, characterized by bone marrow fibrosis grades 2 or 3.
Classified as intermediate-2 or high-risk MF, as defined by the Dynamic International Prognostic Scoring System Plus (DIPSS+).
Must currently be on treatment or have received prior treatment with a single Janus Kinase 2 (JAK2) inhibitor, ruxolitinib, and meet one of the following criteria (in addition to the minimum splenomegaly and symptom burden also required for eligibility):
Treatment with ruxolitinib for >= 24 weeks that was stopped due to lack of spleen response (refractory), or loss of spleen response or symptom control after a previous response (relapsed), or was continued despite relapsed/refractory status.
Treatment with ruxolitinib for < 24 weeks with documented disease progression while on therapy as defined by any of the following:
Appearance of new splenomegaly that is palpable to at least 5 cm below the left costal margin (LCM) in participants with no evidence of splenomegaly prior to the initiation of ruxolitinib.
A >= 100% increase in the palpable distance below the LCM in participants with measurable spleen distance 5 to 10 centimeters (cm) prior to the initiation of ruxolitinib.
A >= 50% increase in the palpable distance below the LCM in participants with measurable spleen distance > 10 cm prior to the initiation of ruxolitinib.
A spleen volume increase of >= 25% (as assessed by Magnetic Resonance Imaging [MRI] or Computed Tomography [CT] scan) in participants with a spleen volume assessment prior to the initiation of ruxolitinib.
Prior treatment with ruxolitinib of at least 10 mg twice daily (BID) for >= 28 days with intolerance defined as new RBC transfusion requirement (at least 2 units/month for 2 months) while receiving a total daily ruxolitinib dose of >= 30 mg but unable to reduce dose further due to lack of efficacy.
Note: Participant must not require a ruxolitinib dose less than 10 mg BID (20 mg daily) due to prior history of ruxolitinibrelated ≥ Grade 3 toxicity.
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
Splenomegaly defined as palpable spleen measurement >= 5 cm below left costal margin or spleen volume >= 450 cm3 as assessed centrally by MRI or CT scan.
Baseline platelet count >= 100 × 10^9/L.
Exclusion Criteria:
Received prior treatment with a BH3-mimetic compound, bromodomain and extra-terminal (BET) inhibitor, or prior use of > 1 JAK2 inhibitor or stem cell transplant.
Eligible for stem cell transplantation at the time of study entry.
Receiving medication that interferes with coagulation or platelet function within 3 days prior to the first dose of study drug or during the study treatment period except for low dose aspirin (up to 100 mg daily) and low molecular weight heparin (LMWH).
Receiving anticancer therapy for an active malignancy or MF including chemotherapy, radiation therapy, hormonal therapy such that at least 5 half-lives of that medication is completed at least 7 days prior to the first dose of study drug or within 30 days prior to first dose of study drug, whichever is shorter, and during the study treatment period (other than any overlapping therapy as part of the selected BAT).
Check Your Eligibility
Let’s see if you might be eligible for this study.
What is your age and gender ?
There are 199 Locations for this study
Chandler Arizona, 85224, United States
Springdale Arkansas, 72762, United States
La Jolla California, 92093, United States
Long Beach California, 90806, United States
Whittier California, 90603, United States
Grand Junction Colorado, 81501, United States
Augusta Georgia, 30912, United States More Info
Columbus Georgia, 31904, United States
Elk Grove Village Illinois, 60007, United States
Maywood Illinois, 60153, United States
Indianapolis Indiana, 46237, United States
New Orleans Louisiana, 70112, United States
New Orleans Louisiana, 70121, United States
Bethesda Maryland, 20817, United States
Detroit Michigan, 48202, United States
Royal Oak Michigan, 48073, United States
Saint Louis Missouri, 63110, United States
Florham Park New Jersey, 07932, United States
Greenvale New York, 11548, United States
New York New York, 10016, United States
New York New York, 10065, United States
Winston-Salem North Carolina, 27157, United States
Cleveland Ohio, 44109, United States
Philadelphia Pennsylvania, 19104, United States More Info
Philadelphia Pennsylvania, 19111, United States
Houston Texas, 77030, United States
San Antonio Texas, 78229, United States
Salt Lake City Utah, 84106, United States
Fairfax Virginia, 22031, United States
Everett Washington, 98201, United States
Yakima Washington, 98902, United States
Green Bay Wisconsin, 54301, United States
Darlinghurst New South Wales, 2010, Australia
East Albury New South Wales, 2640, Australia
Waratah New South Wales, 2298, Australia
Melbourne Victoria, 3004, Australia
Perth Western Australia, 6000, Australia
Sankt Poelten Niederoesterreich, 3100, Austria
Linz Oberoesterreich, 4010, Austria
Wels Oberoesterreich, 4600, Austria
Graz Steiermark, 8010, Austria
Vienna Wien, 1090, Austria
Wien , 1140, Austria
Woluwe-Saint-Lambert Bruxelles-Capitale, 1200, Belgium
Charleroi Hainaut, 6000, Belgium
Gent Oost-Vlaanderen, 9000, Belgium
Roeselare West-Vlaanderen, 8800, Belgium
Antwerp , 2060, Belgium
Sint-Niklaas , 9100, Belgium
Sofiya Sofia, 1431, Bulgaria
Pleven , 5800, Bulgaria
Sofia , 1407, Bulgaria
Sofia , 1431, Bulgaria
Varna , 9010, Bulgaria
Hamilton Ontario, L8V 1, Canada
Ottawa Ontario, K1H 8, Canada
Levis Quebec, G6V 3, Canada More Info
Montreal Quebec, H4A 3, Canada
Zagreb Grad Zagreb, 10000, Croatia
Zagreb Grad Zagreb, 10000, Croatia
Zagreb Grad Zagreb, 10000, Croatia
Osijek Osjecko-baranjska Zupanija, 31000, Croatia
Split Splitsko-dalmatinska Zupanija, 21000, Croatia
Brno , 625 0, Czechia
Praha , 128 0, Czechia
Aalborg Nordjylland, 9000, Denmark
Roskilde Sjælland, 4000, Denmark
Pierre Benite CEDEX Auvergne-Rhone-Alpes, 69495, France
Nimes CEDEX 9 Gard, 30029, France
Pessac Gironde, 33604, France
Bobigny Ile-de-France, 93000, France
Nantes Pays-de-la-Loire, 44000, France
Chambery Savoie, 73000, France
Angers , 49933, France
Paris , 75010, France
Mannheim Baden-Wuerttemberg, 68167, Germany
Mutlangen Baden-Wuerttemberg, 73557, Germany
Augsburg Bayern, 86150, Germany
Dresden Sachsen, 01307, Germany
Bochum , 44791, Germany
Chemnitz , 09116, Germany
Hamburg , 22081, Germany
Munich , 81675, Germany
Rostock , 18057, Germany
Athens Attiki, 11527, Greece
Athens , 10676, Greece
RION Patras Achaia , 26504, Greece
Thessaloniki , 57010, Greece
Szeged Csongrad, 6720, Hungary
Szekesfehervar Fejer, 8000, Hungary
Debrecen Hajdu-Bihar, 4032, Hungary
Kaposvár Somogy, 7400, Hungary
Nyiregyhaza Szabolcs-Szatmar-Bereg, 4400, Hungary
Ramat Gan Tel-Aviv, 52656, Israel
Tel Aviv-Yafo Tel-Aviv, 64239, Israel
Jerusalem Yerushalayim, 91120, Israel
Afula , 18341, Israel
Ashdod , 77476, Israel
Be'Er Ya'Akov , 70300, Israel
Haifa , 31096, Israel
Haifa , 34362, Israel
Nahariya , 22100, Israel
Petakh Tikva , 49414, Israel
Rome Lazio, 00161, Italy
Rome Lazio, 00168, Italy
Monza Monza E Brianza, 20900, Italy
Ancona , 60126, Italy
Bergamo , 24127, Italy
Bologna , 40138, Italy
Catania , 95123, Italy
Florence , 50134, Italy
Napoli , 80131, Italy
Palermo , 90127, Italy
Reggio Calabria , 89124, Italy
Turin , 10126, Italy
Udine , 33100, Italy
Varese , 21100, Italy
Vicenza , 36100, Italy
Nagoya-shi Aichi, 453-8, Japan
Toyoake-shi Aichi, 470-1, Japan
Chiba-shi Chiba, 260-8, Japan
Kashiwa-shi Chiba, 277-8, Japan
Toon-shi Ehime, 791-0, Japan
Fukuoka-shi Fukuoka, 812-8, Japan
Fukushima-shi Fukushima, 960-1, Japan
Gifu-shi Gifu, 501-1, Japan
Sapporo-shi Hokkaido, 003-0, Japan
Kobe-shi Hyogo, 650-0, Japan
Kanazawa-shi Ishikawa, 920-8, Japan
Shiwa-gun Iwate, 028-3, Japan
Kamakura-shi Kanagawa, 247-8, Japan
Kumamoto-shi Kumamoto, 862-8, Japan
Kyoto-shi Kyoto, 606-8, Japan
Tsu-shi Mie, 514-8, Japan
Miyazaki-shi Miyazaki, 889-1, Japan
Niigata-shi Niigata, 951-8, Japan
Kurashiki-shi Okayama, 710-8, Japan
Suita-shi Osaka, 565-0, Japan
Koshigaya-shi Saitama, 343-8, Japan
Izunokuni-shi Shizuoka, 410-2, Japan
Bunkyo-ku Tokyo, 113-8, Japan
Bunkyo-ku Tokyo, 113-8, Japan
Shinjuku-ku Tokyo, 160-0, Japan
Chuo-shi Yamanashi, 409-3, Japan
Busan , 49241, Korea, Republic of
Incheon , 21565, Korea, Republic of
Seoul , 03080, Korea, Republic of
Seoul , 06351, Korea, Republic of
Seoul , 06591, Korea, Republic of
Papatoetoe Auckland, 2025, New Zealand
Lodz Lodzkie, 93-51, Poland
Lublin Lubelskie, 20-08, Poland
Krakow Malopolskie, 31-50, Poland
Warszawa Mazowieckie, 01-74, Poland
Gdansk Pomorskie, 80-21, Poland
Pila Wielkopolskie, 64-92, Poland
Katowice , 40-51, Poland
Poznan , 60-56, Poland
Warszawa , 02-17, Poland
San Juan , 00927, Puerto Rico
Moscow Moskva, 12528, Russian Federation
Moscow , 12764, Russian Federation
Sankt-Peterburg , 19102, Russian Federation
Sankt-Peterburg , 19734, Russian Federation
Tula , 30005, Russian Federation
Belgrade Beograd, 11000, Serbia
Belgrade Beograd, 11080, Serbia
Novi Sad Vojvodina, 21000, Serbia
Johannesburg Gauteng, 2193, South Africa
Pretoria Gauteng, 0044, South Africa
Santiago de Compostela A Coruna, 15706, Spain
Oviedo Asturias, 33011, Spain
Badalona Barcelona, 08916, Spain
Las Palmas de Gran Canaria Las Palmas, 35019, Spain
A Coruna , 15006, Spain
Barcelona , 08003, Spain
Barcelona , 08035, Spain
Madrid , 28041, Spain
Madrid , 28046, Spain
Malaga , 29011, Spain
Salamanca , 37711, Spain
Sevilla , 41013, Spain
Valencia , 46010, Spain
Lund Skane Lan, SE 22, Sweden
Basel Basel-Stadt, 4031, Switzerland
Bern , 3010, Switzerland
Kaohsiung City Kaohsiung, 833, Taiwan
Kaohsiung , 807, Taiwan
Taichung , 40447, Taiwan
Tainan City , 73657, Taiwan
Taipei , 11217, Taiwan
Taoyuan City , 333, Taiwan
Ankara , 06010, Turkey
Edirne, Istanbul , 22030, Turkey
Izmir , 35040, Turkey
Mersin , 33343, Turkey
Samsun , 55200, Turkey
Lincoln Lincolnshire, LN2 4, United Kingdom
London London, City Of, SE1 9, United Kingdom
Great Yarmouth Norfolk, NR31 , United Kingdom
Birmingham , B15 2, United Kingdom
Edinburgh , EH3 9, United Kingdom
Newcastle upon Tyne , NE7 7, United Kingdom
How clear is this clinincal trial information?