Essential Thrombocythemia (ET) Clinical Trial
— Ruxo-BEATOfficial title:
Ruxolitinib Versus Best Available Therapy in Patients With High-risk Polycythemia Vera or High-risk Essential Thrombocythemia - The Ruxo-BEAT Trial
Verified date | January 2024 |
Source | RWTH Aachen University |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
The Philadelphia chromosome negative myeloproliferative neoplasms (MPN) comprise a group of clonal hematological malignancies that are characterized by chronic myeloproliferation, splenomegaly, different degrees of bone marrow fibrosis, and disease-related symptoms including pruritus, night sweats, fever, weight loss, cachexia, and diarrhea. In addition, due to elevated numbers of leucocytes, erythrocytes and/or platelets, the disease course can be complicated by thromboembolic disease, hemorrhage, and leukemic transformation as well as myelofibrosis. Patients with polycythemia vera (PV) typically harbor an increased number of blood cells from all three hematopoietic cell lineages due to clonal amplification of hematopoetic stem cells, while patients with essential thrombocythemia (ET) typically show a predominant expansion of the megakaryocytic lineage. Most patients with PV below the age of 60 years are currently being treated with acetylsalicylic acid +/- phlebotomy only, and patients with low-risk ET have an almost normal life expectancy and often do not require specific treatment. However, PV- as well as ET-patients with a higher risk for complications require cytoreductive treatment. In addition, constitutional symptoms can be unbearable to patients even in the absence of bona fide high risk factors, and these patients may similarly benefit from antineoplastic therapy.
Status | Active, not recruiting |
Enrollment | 207 |
Est. completion date | December 2028 |
Est. primary completion date | December 2027 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: 1. Subjects must provide written informed consent prior to studyspecific procedures or assessments which are not routinely performed for diagnosis or monitoring of PV or ET, and the subjects must be willing to comply with treatment and to follow up assessments and procedures 2. Patient must be 18 years of age or older 3. Patient´s ECOG performance status must be 0-2 4. Patient must fulfill WHO 2008 diagnostic criteria for either polycythemia vera (PV) or essential thrombocythemia (ET). Moreover, PV- and ET-patients have to be classified as high risk according to defined criteria. For patients with high risk PV OR PV with indication for cytoreductive therapy due to progressive myeloproliferation, AT LEAST ONE of the following must be fulfilled (according to DGHO onkopedia) (Barbui, et al., 2011). (Passamonti, 2009): - Age > 60 years - Previous documented thrombosis or thromboembolism - Platelet count > 1500 x 109/L - Poor tolerance of phlebotomy or frequent phlebotomy requirement - Symptomatic or progressive splenomegaly - Severe disease-related symptoms (according to the investigators definition) - Progressive leukocytosis with leukocyte count > 20 x 109/L For patients with high risk ET, AT LEAST ONE of the following must be fulfilled (according to DGHO guidelines): - Age > 60 years - Platelet count> 1500 x 109/L - Previous thrombosis or thromboembolism - Previous severe hemorrhage related to ET (defined as decrease of Hgb of at least 2 g/dl) 5. Patients must fulfill the following criteria regarding prior therapy: PV patients: Never treated with cytoreductive drugs except hydroyurea, anagrelide, or interferon for up to 6 weeks maximum (phlebotomy and/or aspirin are allowed) ET patients: Naïve and pretreated patients may be entered in this trial. 6. Patient must have adequate liver function as indicated by a total bilirubin, AST, and ALT = 2 of the institutional upper limit of normal (ULN) value, unless directly attributable to the patient's MPN 7. Patient must have a creatinine clearance >40ml/min calculated according to the modified formula of Cockcroft and Gault, eGFR, or directly measured after 24h-urine collection 8. Patients must be able to swallow and retain oral medication Exclusion Criteria: 1. Patients who meet criteria for post PV-MF or post ET-MF (IWG-MRT) 2. Patients who have received previous ruxolitinib treatment 3. Patients who have a history of anaphylaxis following exposure to the BAT drug of choice 4. Patients who have an inadequate bone marrow reserve as demonstrated by ANC = 1 x 109/l OR platelet count <50 x 109/l 5. Patients who have known hepatitis B or C or HIV infection 6. Patients who suffer from other severe, concurrent diseases, including tuberculosis, serious cardiac functional dysfunction (class III or IV as defined by the New York Heart Association Classification), uncontrolled diabetes, uncontrolled hypertension, severe pulmonary disease (i.e. COPD with hypoxemia), or major organ malfunction that could interfere with the patient's ability to participate in the study 7. Patients who have history of active substance or alcohol abuse within the last year 8. Female patients who are pregnant or nursing 9. Patients who have participated in another interventional trial and/or used investigational agents or concurrent anticancer treatment for concomitant disease within the last 4 weeks of registration 10. Any circumstance at the time of study entry that would preclude completion of the study or the required follow-up prohibits inclusion into this study 11. Subjects who have had an active malignancy during the previous 3 years except for treated cervical intraepithelial neoplasia, basal cell carcinoma of the skin, or squamous cell carcinoma of the skin, each with no evidence for recurrence in the past 3 years 12. Patients who have uncontrolled bacterial, viral, or fungal infection 13. Patients who have any medical condition requiring prolonged use of oral corticosteroids with a dose of more than 20 mg per day (> 1 month) 14. Patients who have severe cerebral dysfunction and/or legal incapacity 15. Patients who have had active splanchnic vein thrombosis within the last 3 months (includes Budd-Chiari, portal vein, splenic and mesenteric thrombosis) 16. Patients who have thyroid dysfunction which is not adequately controlled 17. Fertile men or women of childbearing potential cannot be included unless they are: - surgically sterile or > 2 years after the onset of menopause and/or - willing to use a highly effective contraceptive method (Pearl Index <1) such as oral contraceptives, intrauterine device, sexual abstinence, or barrier method of contraception (i.e. condoms) in conjunction with spermicidal jelly during study treatment 18. Patients who are taking any of the following prohibited medication: - clarithromycin, telithromycin, troleandomycin (antibiotics) - ritonavir, indinavir, saquinavir, nelfinavir, amprenavir, lopinavir (HIV protease inhibitors) - itraconazole, ketoconazole, voriconazole, fluconazole (antifungals) 19. Patients with a diagnosis of galactose or lactose intolerance or a glucose-galactose- malabsortion |
Country | Name | City | State |
---|---|---|---|
Germany | Uniklinik RWTH Aachen | Aachen | NRW |
Germany | Studienzentrum Aschaffenburg | Aschaffenburg | Bayern |
Germany | Charite Universitätsmedizin Berlin; Medizinische Klinik m.S. Hämatologie, Onkologie und Tumorimmunologie | Berlin | |
Germany | Universitätsklinikum Bonn Medizinische Klinik und Poliklinik III | Bonn | Nordrhein-Westfalen |
Germany | Klinikum Chemnitz gGmbH Klinik für Innere Medizin III | Chemnitz | Sachsen |
Germany | Universitätsklinikum Dresden Medizinische Klinik und Poliklinik I | Dresden | Sachsen |
Germany | Johanniter-Krankenhaus Rheinhausen GmbH Hämatologie / Internistische Onkologie / Tagesklinik | Duisburg | Nordrhein-Westfalen |
Germany | Marienhospital | Düsseldorf | North Rhine Westphalia |
Germany | Universitätsklinikum Düsseldorf Klinik für Hämatologie, Onkologie und Klinische Immunologie | Düsseldorf | Nordrhein-Westfalen |
Germany | Universitätsklinikum Essen Klinik für Hämatologie | Essen | Nordrhein-Westfalen |
Germany | Universitätsklinikum Freiburg - Klinik für Innere Medizin I | Freiburg | |
Germany | Universitätsklinikum Halle (Saale) | Halle (Saale) | Sachsen-Anhalt |
Germany | Universitätsklinikum Hamburg Eppendorf Klinik und Poliklinik für Onkologie, Hämatologie und KMT mit Sektion Pneumologie | Hamburg | |
Germany | Universitätsklinik Jena - Klinik für Innere Medizin II | Jena | |
Germany | UNIVERSITÄTSKLINIKUM Schleswig-Holstein - Klinik für Hämatologie und Onkologie, Campus Lübeck | Lübeck | |
Germany | Universitätsklinikum Magdeburg | Magdeburg | Sachesen-Anhalt |
Germany | Universitätsmedizin Mainz III. Medizinische Klinik und Poliklinik | Mainz | Hessen |
Germany | Universitätsmedizin Mannheim III. Medizinische Klinik Hämatologie und Internistische Onkologie | Mannheim | Baden-Württemberg |
Germany | Mühlenkreiskliniken Johannes Wesling Klinikum Minden Klinik für Hämatologie, Onkologie und Palliativmedizin | Minden | Nordrhein-Westfalen |
Germany | III. Medizinischen Klinik des Klinikums rechts der Isar der TU München | Müchen | Bayern |
Germany | Klinikum Nürnberg Nord Medizinische Klinik 5 | Nürnberg | Bayern |
Germany | Universitätsklinikum Ulm Klinik für Innere Medizin III | Ulm | Baden-Württemberg |
Germany | Rems-Murr Klinikum Winnenden | Winnenden | Baden-Württemberg |
Lead Sponsor | Collaborator |
---|---|
RWTH Aachen University | Novartis Pharmaceuticals |
Germany,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | The rate of complete clinicohematologic response rate (CHR) as defined by Barosi et al 2009 | at month 6 | ||
Secondary | Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | at month 6 and 12 | ||
Secondary | The complete response rate (CR) at month 6 as defined by Barosi et al Blood 2013 (revised ELN response criteria) | month 6 | ||
Secondary | The rate of complete responses (CHR) at month 12 as defined by Barosi et al Blood 2009 | month 12 | ||
Secondary | The efficacy as assessed by the absence of phlebotomy (Hct <45%) | through study completion, an average of 2 years | ||
Secondary | The efficacy as assessed by the reduction in spleen size (palpable spleen that is reduced by > 50% from baseline measured by palpation and ultrasound) OR platelet count < 600 x 10^9/l (ET) | through study completion, an average of 2 years | ||
Secondary | Proportion of subjects achieving both durable absence of phlebotomy eligibility AND durable spleen volume reduction measured by palpation and ultrasound (PV) OR durable platelet count <600 x 10^9/l (ET) (durable defined as >3 months) {Barosi et al 2013) | through study completion, an average of 2 years | ||
Secondary | The rate of overall clinicohematologic remissions (CR + PR) according to both guidelines (Barosi et al 2009 and 2013) | through study completion, an average of 2 years | ||
Secondary | Safety of both regimen | Adverse events will be assessed according to CTCAE 4.0 throughout the study until 30 days after EoT for patients in both regimens | through study completion, an average of 2 years |
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