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

• Status: Active, not recruiting
• Trial end date: 2027-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: RWTH Aachen University
• Collaborators: Novartis; Novartis Pharmaceuticals
• Treatments: Hydroxyurea

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, AT LEAST 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, AT LEAST 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 short- term therapy (up to 6 weeks maximum) with ONE of the following drugs: hydroxyurea, anagrelide, or interferon (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