Myeloproliferative Neoplasms (MPN): high-risk Polycythemia Vera (PV) and high-risk Essential Thrombocythemia (ET)
Conditions
Interventions
Trade Name: Jakavi® 5 mg tablets
Product Name: Ruxolitinib
Product Code: INC424
Pharmaceutical Form: Tablet
INN or Proposed INN: Ruxolitinib
CAS Number: 1092939-17-7
Current Sponsor code: INC424
Other
Sponsors
University Hospital Aachen AöR, represented by the executive board, represented by the Dean of the Medical Faculty
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects must provide written informed consent prior to study-specific 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 as outlined below. - 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 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. 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. Patient must be able to swallow and retain oral medication Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 380 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 380
Exclusion criteria
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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of the Ruxo-BEAT trial is to assess the feasibility, safety, and efficacy of administration of ruxolitinib vs. best available therapy in patients with high-risk PV or high-risk ET. Primary Endpoint •The rate of complete clinicohematologic responses (CHR) at month 6 compared to baseline as defined by Barosi et al., 2009.;Secondary Objective: •Safety of both regimens •The rate of complete clinicohematologic responses at month 12 & 24 as defined by Barosi et al. 2009 (with the clinical modification that splenomegaly assessment may be done by ultrasound or palpation) •To determine the complete response rate at month 6 as defined by Barosi et al. 2013 (revised ELN response criteria) •The efficacy as assessed by both the absence of phlebotomy (Hct 50% from baseline measured by palpation or ultrasound) OR platelet count 3 months) (Barosi et al. 2009/2013) at month 6, 12 & 24 •The rate of overall clinicohematologic responses (CR+PR) according to both guidelines (Barosi et al. 2009 and 2013) at month 6 & 24;Primary end point(s): •The rate of complete clinicohematologic responses (CHR) at month 6 compared to baseline as defined by Barosi et al 2009;Timepoint(s) of evaluation of this end point: EOT | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Safety of both regimens • The rate of complete clinicohematologic responses (CHR) at month 12 and month 24 as defined by Barosi et al. Blood 2009 (with the clinical modification that splenomegaly assessment may be done by ultrasound or palpation) • To determine the complete response (CR) rate at month 6 as defined by Barosi et al. Blood 2013 (revised ELN response criteria, see section 15.6) (Barosi, et al., 2013) • The efficacy as assessed by both the absence of phlebotomy (Hct 50% from baseline measured by palpation or ultrasound) OR platelet count 3 months) (Barosi et al. 2009/2013) at month 6, month 12 and month 24 • The rate of overall clinicohematologic responses (CR + PR) according to both guidelines (Barosi et al. 2009 and 2013) at month 6 and month 24 ;Timepoint(s) of evaluation of this end point: EOT | — |
Countries
Germany
Contacts
Public ContactCTC-A
Center for Translational & Clinical Research Aachen (CTC-A)
Outcome results
None listed