This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

The Ruxo-BEAT Trial in Patients With High-risk Polycythemia Vera or High-risk Essential Thrombocythemia (Ruxo-BEAT)

This study is currently recruiting participants.
See Contacts and Locations
Verified May 2017 by RWTH Aachen University
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
RWTH Aachen University
ClinicalTrials.gov Identifier:
NCT02577926
First received: October 1, 2015
Last updated: May 18, 2017
Last verified: May 2017
  Purpose

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.


Condition Intervention Phase
Polycythemia Vera (PV) Essential Thrombocythemia (ET) Drug: Ruxolitinib Drug: BAT Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Ruxolitinib Versus Best Available Therapy in Patients With High-risk Polycythemia Vera or High-risk Essential Thrombocythemia - The Ruxo-BEAT Trial

Resource links provided by NLM:


Further study details as provided by RWTH Aachen University:

Primary Outcome Measures:
  • The rate of complete clinicohematologic response rate (CHR) as defined by Barosi et al Blood 2009 [ Time Frame: at month 6 ]
    The rate of complete clinicohematologic response rate (CHR) as defined by Barosi et al Blood 2009


Secondary Outcome Measures:
  • Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: at month 6 and 12 ]
  • The complete response rate (CR) at month 6 as defined by Barosi et al Blood 2013 (revised ELN response criteria) [ Time Frame: month 6 ]
  • The rate of complete responses (CHR) at month 12 as defined by Barosi et al Blood 2009 [ Time Frame: month 12 ]
  • The efficacy as assessed by the absence of phlebotomy (Hct <45%) [ Time Frame: through study completion, an average of 2 years ]
  • 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) [ Time Frame: through study completion, an average of 2 years ]
  • 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) [ Time Frame: through study completion, an average of 2 years ]
  • The rate of overall clinicohematologic remissions (CR + PR) according to both guidelines (Barosi et al 2009 and 2013) [ Time Frame: through study completion, an average of 2 years ]

Estimated Enrollment: 380
Actual Study Start Date: October 2015
Estimated Study Completion Date: December 2020
Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ruxolitinib
Ruxolitinib will be administered orally at a dose of 10 mg twice daily (both PV and ET) for two consecutive years.
Drug: Ruxolitinib
Ruxolitinib is a JAK1/2-specific tyrosine kinase inhibitor (TKI) which has been approved for the treatment of symptomatic myelofibrosis. The compound was shown to be superior to hydroxyurea in reducing splenomegaly and constitutional symptoms.
Other Names:
  • Study drug
  • Jakavi
Active Comparator: Best available therapy (BAT)
BAT may include all currently used treatment options. BAT is at the choice of the investigator (monotherapy with i.e. hydroxyurea, anagrelide, interferon, busulfan, immunomodulators etc). BAT will be administrated for two consecutive years.
Drug: BAT
BAT is at the choice of the investigator (monotherapy with i.e. hydroxyurea, anagrelide, interferon, busulfan, immunomodulators etc).
Other Name: Controll Treatment

Detailed Description:

Polycythemia vera (PV) and essential thrombocythemia (ET) are classical Philadelphia-negative myeloproliferative neoplasms (MPN) that are characterized by an excess of cells in the peripheral blood, clonal bone marrow hyperplasia, and extramedullary hematopoiesis. The symptoms of these patients may range from asymptomatic disease to symptomatic disease that may significantly affect their activities of daily living, such as severe generalized pruritus, night sweats and fevers, erythromelalgia, bone and muscle pain, weight loss, and fatigue. Moreover, the patients may develop thromboembolic and hemorrhagic complications, transition to myelofibrosis (MF), and transformation to acute leukemia. In principle, the only potentially curative therapy for MPNs is allogenic stem cell transplantation (allo-SCT). However, due to significant transplant-associated morbidity and mortality, this therapeutic option is only applied in exceptional cases of ET or PV. The majority of patients do not qualify for allo-SCT since the risks of this treatment clearly outweigh the potential benefits. Moreover, even with a non-transplantation approach, patients with ET and PV have a life expectancy comparable to or close to healthy age-matched control persons. For patients with standard risk PV, phlebotomy and acetylsalicylic acid are standard of care (target hematocrit below 45 %), while patients with standard risk ET should receive either no specific treatment or acetylsalicylic acid (provided that no microvascular symptoms or secondary acquired von Willebrand syndrome are present).

However, in patients who are at high risk to develop thromboembolic or hemorrhagic complications (high-risk patients), cytoreductive treatment is generally indicated to prevent these potentially life-threatening complications. In PV and ET, high risk patients are characterized by advanced age (> 60 years) and / or a history of thromboembolic or hemorrhagic events {1,2,3}. In ET, a platelet count > 1500 x 109/l is associated with an increased risk of bleeding, and thus should result in a platelet lowering treatment {2}. In PV, in addition to the risk-score based therapy, cytoreduction is also required in patients with progressive or marked myeloproliferation (leukocytosis, thrombocytosis, symptomatic splenomegaly, increase of frequency of phlebotomy requirement), or devastating constitutional symptoms {1,2,4}. In Germany, best available therapy (BAT) includes approved drugs such as hydroxyurea (HU; approved for both PV and ET) and anagrelide (approved for second-line treatment of ET) and non-approved options such as alpha-interferon, pipobroman, busulfan (in elderly patients), and radioactive phosphorus (32P). In rare cases, patients may also benefit from splenic irradiation or splenectomy.

Ruxolitinib is a JAK1/2-specific tyrosine kinase inhibitor (TKI) which has been approved for the treatment of symptomatic myelofibrosis. The compound was shown to be superior to hydroxyurea in reducing splenomegaly and constitutional symptoms. Ruxolitinib is currently studied in phase 2 and phase 3 clinical trials for HU-resistant or HU-intolerant PV and ET. The aim of the present study is to assess the feasibility, efficacy, and safety of ruxolitinib treatment vs. BAT in patients with high-risk PV or -ET.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. written informed consent and willing to comply with treatment and to follow up assessments and procedures
  2. >18 years old
  3. Patient´s ECOG performance status: 0-2
  4. Patient must fulfill WHO 2008 diagnostic criteria for either PV or ET. 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, ONE of the following must be fulfilled:

    • Age >60 years
    • Previous documented thrombosis or thromboembolism
    • Platelet count > 1500 x 10^9/L
    • Poor tolerance of phlebotomy or frequent phlebotomy requirement
    • Symptomatic or progressive splenomegaly
    • Severe disease-related symptoms
    • Progressive leukocytosis with leukocyte count > 20 x 10^9/L

    For patients with high risk ET, ONE of the following must be fulfilled:

    • Age > 60 years
    • Platelet count> 1500 x 10^9/L
    • Previous thrombosis or thromboembolism
    • Previous severe hemorrhage related to ET.
  5. Patients must fulfill the following criteria regarding prior therapy:

PV patients: Never treated with cytoreductive drugs except hydroxyurea, 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 7. adequate liver function, AST, and ALT ≤ 2 the institutional ULN value, unless directly attributable to the patient's MPN 8. creatinine clearance >40ml/min calculated according to the modified formula of Cockcroft and Gault, eGFR, or directly measured after 24h-urine collection 9. ability to swallow and retain oral medication

Exclusion Criteria:

  1. criteria for post PV-MF or post ET-MF are met
  2. previous ruxolitinib treatment
  3. history of anaphylaxis following exposure to the BAT drug of choice
  4. inadequate bone marrow reserve as demonstrated by ANC ≤ 1 x 10^9/l OR platelet count <50 x 10^9/l
  5. known hepatitis B or C or HIV infection
  6. other severe, concurrent diseases, including tuberculosis, serious cardiac functional dysfunction (class III or IV), uncontrolled diabetes, uncontrolled hypertension, severe pulmonary disease, or major organ malfunction
  7. history of active substance or alcohol abuse within the last year
  8. Female patients who are pregnant or nursing
  9. participation 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 circumstances at the time the study entry that would preclude completion of the study or the required follow-up prohibits inclusion into this study
  11. 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. active bacterial, viral, or fungal infection
  13. medical condition requiring prolonged use of oral corticosteroids with a dose of more than 20 mg per day (> 1 month)
  14. severe cerebral dysfunction and/or legal incapacity
  15. history of active splanchnic vein thrombosis within the last 3 months (includes Budd-Chiari, portal vein, splenic and mesenteric thrombosis)
  16. 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)
  18. patients who are taking any of the following prohibited medication: clarithromycin, telithromycin, troleandomycin, ritonavir, indinavir, saquinavir, nelfinavir, amprenavir, lopinavir -itraconazole, ketoconazole, voriconazole, fluconazole
  19. Patients who suffer from galactose intolerance, lack of lactose or a glucose-galactose-malabsortion
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02577926

Contacts
Contact: Susanne Isfort, Dr. 00492418037411 sisfort@ukaachen.de
Contact: Verena Deserno +49241803380092 vdeserno@ukaachen.de

Locations
Germany
Universitätsmedizin Mannheim III. Medizinische Klinik Hämatologie und Internistische Onkologie Recruiting
Mannheim, Baden-Württemberg, Germany, 68167
Contact: Eva Langfelder, Prof. Dr.    +49 (0)621 383 41 31    eva.lengfelder@umm.de   
Universitätsklinikum Ulm Klinik für Innere Medizin III Recruiting
Ulm, Baden-Württemberg, Germany, 89081
Contact: Konstanz Döhner, Prof. Dr.    +49 (0)731 500 45543    konstanze.doehner@uniklinik-ulm.de   
Rems-Murr Klinikum Winnenden Recruiting
Winnenden, Baden-Württemberg, Germany, 71364
Contact: Stefani Parmentier, Dr.       stefani.parmentier@rems-murr-kliniken.de   
Contact: Markus Schaich, Dr.       markus.schaich@rems-murr-kliniken.de   
Studienzentrum Aschaffenburg Recruiting
Aschaffenburg, Bayern, Germany, 63739
Contact: Martine Klausmann, Dr.       mk@klausmann.de   
III. Medizinischen Klinik des Klinikums rechts der Isar der TU München Recruiting
Müchen, Bayern, Germany, 81675
Contact: Philipp Jost, Dr. med.       philipp.jost@tum.de   
Klinikum Nürnberg Nord Medizinische Klinik 5 Recruiting
Nürnberg, Bayern, Germany, 90419
Contact: Marinela Augustin, Dr.    +49 (0) 911 398 3085    Marinela.Augustin@klinikum-nuernberg.de   
Universitätsmedizin Mainz III. Medizinische Klinik und Poliklinik Recruiting
Mainz, Hessen, Germany, 55131
Contact: Thomas Kindler, PD Dr.    +49 (0)6131 17-5046    thomas.kindler@unimedizin-mainz.de   
Universitätsklinikum Bonn Medizinische Klinik und Poliklinik III Recruiting
Bonn, Nordrhein-Westfalen, Germany, 53105
Contact: Dominik Wolf, Prof. Dr.    +49 (0)228 287 17233    dominik.wolf@ukb.uni-bonn.de   
Johanniter-Krankenhaus Rheinhausen GmbH Hämatologie / Internistische Onkologie / Tagesklinik Recruiting
Duisburg, Nordrhein-Westfalen, Germany, 47228
Contact: Jan Sebastian Balleisen, Dr. med.       s.balleisen@johanniter-rheinhausen.de   
Universitätsklinikum Düsseldorf Klinik für Hämatologie, Onkologie und Klinische Immunologie Recruiting
Düsseldorf, Nordrhein-Westfalen, Germany, 40225
Contact: Norbert Gattermann, Prof. Dr.       gattermann@med.uni-duesseldorf.de   
Universitätsklinikum Essen Klinik für Hämatologie Recruiting
Essen, Nordrhein-Westfalen, Germany, 45122
Contact: Göthert Joachim, Dr.       joachim.goethert@uk-essen.de   
Mühlenkreiskliniken Johannes Wesling Klinikum Minden Klinik für Hämatologie, Onkologie und Palliativmedizin Recruiting
Minden, Nordrhein-Westfalen, Germany, 32429
Contact: Martin Griesshammer, Prof. Dr.    +49 (0)571 790 4201    Martin.Griesshammer@muehlenkreiskliniken.de   
Zentralklinikum Medizinische Klinik A Hämatologie, Hämostaseologie, Onkologie und Pneumologie Recruiting
Münster, Nordrhein-Westfalen, Germany, 48149
Contact: Tim Sauer, Dr.    +49 (0) 251 83 52818    tim.sauer@ukmuenster.de   
Uniklinik RWTH Aachen Recruiting
Aachen, NRW, Germany, 52074
Contact: Steffen Koschmieder, Univ.-Prof. Dr. med.    00492418036102    skoschmieder@ukaachen.de   
Contact: Susanne Isfort, Dr-med.    00492418037411    sisfort@ukaachen.de   
Universitätsklinikum Magdeburg Recruiting
Magdeburg, Sachesen-Anhalt, Germany, 39120
Contact: Denise Wolleschak, Dr.    0049 391 6713271    denise.wolleschak@med.ovgu.de   
Klinikum Chemnitz gGmbH Klinik für Innere Medizin III Recruiting
Chemnitz, Sachsen, Germany, 09113
Contact: Hänel Mathias, PD Dr.    +49 (0)371 333 43045    m.haenel@skc.de   
Universitätsklinikum Dresden Medizinische Klinik und Poliklinik I Recruiting
Dresden, Sachsen, Germany, 01307
Contact: Uwe Platzbecker, Prof. Dr.    +49 (0)351 - 458 2583    uwe.platzbecker@uniklinikum-dresden.de   
Charité Universitätsmedizin Berlin Med. Klinik m.S. Hämatologie, Onkologie und Tumorimmunologie Recruiting
Berlin, Germany, 13353
Contact: Philipp LeCoutre, PD Dr.    +49 30 450 665 307    philipp.lecoutre@charite.de   
Universitätsklinikum Freiburg - Klinik für Innere Medizin I Recruiting
Freiburg, Germany, 79106
Contact: Nikolas von Bubnoff, Prof. Dr.    +49 (0) 761 270-33210    nikolas.bubnoff@uniklinik-freiburg.de   
Universitätsklinikum Hamburg Eppendorf Klinik und Poliklinik für Onkologie, Hämatologie und KMT mit Sektion Pneumologie Recruiting
Hamburg, Germany, 20246
Contact: Philippe Schafhausen, PD Dr.    +49n (0)40 7410 57122    schafhausen@uke.de   
Universitätsklinik Jena - Klinik für Innere Medizin II Recruiting
Jena, Germany, 07705
Contact: Florian Heidel, Prof. Dr.    +49 3641 9-324210    Florian.Heidel@med.uni-jena.de   
Sponsors and Collaborators
RWTH Aachen University
Novartis
Investigators
Principal Investigator: Steffen Koschmieder, Prof. Dr. RWTH University Hospital MK4
  More Information

Responsible Party: RWTH Aachen University
ClinicalTrials.gov Identifier: NCT02577926     History of Changes
Other Study ID Numbers: 12-181
Study First Received: October 1, 2015
Last Updated: May 18, 2017
Individual Participant Data  
Plan to Share IPD: No

Additional relevant MeSH terms:
Thrombocythemia, Essential
Thrombocytosis
Polycythemia
Polycythemia Vera
Blood Coagulation Disorders
Hematologic Diseases
Blood Platelet Disorders
Myeloproliferative Disorders
Bone Marrow Diseases
Hemorrhagic Disorders
Hydroxyurea
Antineoplastic Agents
Antisickling Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on June 27, 2017