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

NCT02577926 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: 12-181
• Study Type: interventional
• Target: 207
• Locations: 1 country
• Sites: 23

Brief Summary

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.

Conditions

Polycythemia Vera (PV); Essential Thrombocythemia (ET)

Outcome Measures

Primary Outcomes (1)

• The rate of complete clinicohematologic response rate (CHR) as defined by Barosi et al 2009

  at month 6

Secondary Outcomes (8)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  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)

  month 6

• The rate of complete responses (CHR) at month 12 as defined by Barosi et al Blood 2009

  month 12

• The efficacy as assessed by the absence of phlebotomy (Hct <45%)

  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)

  through study completion, an average of 2 years

Study Arms (2)

Ruxolitinib

EXPERIMENTAL

Ruxolitinib will be administered orally at a dose of 10 mg twice daily (both PV and ET) for two consecutive years.

Drug: Ruxolitinib

Best available therapy (BAT)

ACTIVE COMPARATOR

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

Interventions

Ruxolitinib DRUG

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.

Also known as: Study drug, Jakavi

Ruxolitinib

BAT DRUG

BAT is at the choice of the investigator (monotherapy with i.e. hydroxyurea, anagrelide, interferon, busulfan, immunomodulators etc).

Also known as: Control Treatment

Best available therapy (BAT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Patient must be 18 years of age or older
• Patient´s ECOG performance status must be 0-2
• 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

You may not qualify if:

• Patients who meet criteria for post PV-MF or post ET-MF (IWG-MRT)
• Patients who have received previous ruxolitinib treatment
• Patients who have a history of anaphylaxis following exposure to the BAT drug of choice
• Patients who have an inadequate bone marrow reserve as demonstrated by ANC ≤ 1 x 109/l OR platelet count \<50 x 109/l
• Patients who have known hepatitis B or C or HIV infection
• 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
• Patients who have history of active substance or alcohol abuse within the last year
• Female patients who are pregnant or nursing
• 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
• 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
• Patients who have uncontrolled bacterial, viral, or fungal infection
• Patients who have any medical condition requiring prolonged use of oral corticosteroids with a dose of more than 20 mg per day (\> 1 month)
• Patients who have severe cerebral dysfunction and/or legal incapacity
• Patients who have had active splanchnic vein thrombosis within the last 3 months (includes Budd-Chiari, portal vein, splenic and mesenteric thrombosis)
• Patients who have thyroid dysfunction which is not adequately controlled

Sponsors & Collaborators

• RWTH Aachen University: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (23)

Universitätsmedizin Mannheim III. Medizinische Klinik Hämatologie und Internistische Onkologie

Mannheim, Baden-Wurttemberg, 68167, Germany

Location

Universitätsklinikum Ulm Klinik für Innere Medizin III

Ulm, Baden-Wurttemberg, 89081, Germany

Location

Rems-Murr Klinikum Winnenden

Winnenden, Baden-Wurttemberg, 71364, Germany

Location

Studienzentrum Aschaffenburg

Aschaffenburg, Bavaria, 63739, Germany

Location

III. Medizinischen Klinik des Klinikums rechts der Isar der TU München

Müchen, Bavaria, 81675, Germany

Location

Klinikum Nürnberg Nord Medizinische Klinik 5

Nuremberg, Bavaria, 90419, Germany

Location

Universitätsklinikum Hamburg Eppendorf Klinik und Poliklinik für Onkologie, Hämatologie und KMT mit Sektion Pneumologie

Hamburg, Hamburg, 20246, Germany

Location

Universitätsmedizin Mainz III. Medizinische Klinik und Poliklinik

Mainz, Hesse, 55131, Germany

Location

Uniklinik RWTH Aachen

Aachen, North Rhine-Westphalia, 52074, Germany

Location

Universitätsklinikum Bonn Medizinische Klinik und Poliklinik III

Bonn, North Rhine-Westphalia, 53105, Germany

Location

Johanniter-Krankenhaus Rheinhausen GmbH Hämatologie / Internistische Onkologie / Tagesklinik

Duisburg, North Rhine-Westphalia, 47228, Germany

Location

Universitätsklinikum Düsseldorf Klinik für Hämatologie, Onkologie und Klinische Immunologie

Düsseldorf, North Rhine-Westphalia, 40225, Germany

Location

Marienhospital

Düsseldorf, North Rhine-Westphalia, 40479, Germany

Location

Universitätsklinikum Essen Klinik für Hämatologie

Essen, North Rhine-Westphalia, 45122, Germany

Location

Mühlenkreiskliniken Johannes Wesling Klinikum Minden Klinik für Hämatologie, Onkologie und Palliativmedizin

Minden, North Rhine-Westphalia, 32429, Germany

Location

Universitätsklinikum Magdeburg

Magdeburg, Sachesen-Anhalt, 39120, Germany

Location

Klinikum Chemnitz gGmbH Klinik für Innere Medizin III

Chemnitz, Saxony, 09113, Germany

Location

Universitätsklinikum Dresden Medizinische Klinik und Poliklinik I

Dresden, Saxony, 01307, Germany

Location

Universitätsklinikum Halle (Saale)

Halle, Saxony-Anhalt, 06120, Germany

Location

Charite Universitätsmedizin Berlin; Medizinische Klinik m.S. Hämatologie, Onkologie und Tumorimmunologie

Berlin, 13353, Germany

Location

Universitätsklinikum Freiburg - Klinik für Innere Medizin I

Freiburg im Breisgau, 79106, Germany

Location

Universitätsklinik Jena - Klinik für Innere Medizin II

Jena, 07705, Germany

Location

UNIVERSITÄTSKLINIKUM Schleswig-Holstein - Klinik für Hämatologie und Onkologie, Campus Lübeck

Lübeck, Germany

Location

Related Publications (2)

• Isfort S, Manz K, Teichmann LL, Crysandt M, Burchert A, Hochhaus A, Saussele S, Kiani A, Gothert JR, Illmer T, Schafhausen P, Al-Ali HK, Stegelmann F, Hanel M, Pfeiffer T, Giagounidis A, Franke GN, Koschmieder S, Fabarius A, Ernst T, Warnken-Uhlich M, Wolber U, Kohn D, Pfirrmann M, Wolf D, Brummendorf TH; German CML study group. Step-in dosing of bosutinib in pts with chronic phase chronic myeloid leukemia (CML) after second-generation tyrosine kinase inhibitor (TKI) therapy: results of the Bosutinib Dose Optimization (BODO) Study. Ann Hematol. 2023 Oct;102(10):2741-2752. doi: 10.1007/s00277-023-05394-0. Epub 2023 Aug 18.

  PMID: 37592092 DERIVED

• Koschmieder S, Isfort S, Wolf D, Heidel FH, Hochhaus A, Schafhausen P, Griesshammer M, Wolleschak D, Platzbecker U, Dohner K, Jost PJ, Parmentier S, Schaich M, von Bubnoff N, Stegelmann F, Maurer A, Crysandt M, Gezer D, Kortmann M, Franklin J, Frank J, Hellmich M, Brummendorf TH; German Study Group for Myeloproliferative Neoplasms (GSG-MPN). Efficacy and safety of ruxolitinib in patients with newly-diagnosed polycythemia vera: futility analysis of the RuxoBEAT clinical trial of the GSG-MPN study group. Ann Hematol. 2023 Feb;102(2):349-358. doi: 10.1007/s00277-022-05080-7. Epub 2022 Dec 23.

  PMID: 36564535 DERIVED

MeSH Terms

Conditions

Polycythemia Vera; Thrombocythemia, Essential

Interventions

ruxolitinib; Drug Evaluation

Condition Hierarchy (Ancestors)

Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Blood Coagulation Disorders; Thrombocytosis; Blood Platelet Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Drug Development; Investigative Techniques; Evaluation Studies as Topic

Study Officials

• Steffen Koschmieder, Prof. Dr.

  RWTH University Hospital MK4

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2015
• First Posted: October 16, 2015
• Study Start: October 1, 2015
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: June 10, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

DE (23)