Ruxolitinib versus Best Available Therapy in patients with high-risk polycythemia vera or high-risk essential thrombocythemia – The Ruxo-BEAT Trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaetsklinikum Aachen AöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

29 Jun 2015 → ongoing

Decision date (initial)

2024-08-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-515619-23-00

EudraCT number

2013-002132-25

ClinicalTrials.gov

NCT02577926

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

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.

Conditions and MedDRA coding

essential thrombocythemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

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 10^9/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 10^9/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 10^9/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

Exclusion criteria 19

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 10^9/l OR platelet count <50 x 10^9/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 glucosegalactose- malabsorption.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The rate of complete clinicohematologic responses (CHR) at month 6, compared to baseline, as defined by (Barosi, et al., 2009).

Secondary endpoints 6

1. Safety of both regimens.
2. 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).
3. 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).
4. The efficacy as assessed by both the absence of phlebotomy (Hct <45%) and reduction in spleen size (palpable spleen that is reduced by > 50% from baseline measured by palpation or ultrasound) OR platelet count < 600 x 10^9/l (ET) at month 6 and month 24
5. The proportion of subjects achieving both durable absence of phlebotomy eligibility and durable spleen size reduction measured by palpation (PV) OR durable platelet count < 600 x 10^9/l (ET) (durable defined as > 3 months) (Barosi et al. 2009/2013) at month 6, month 12 and month 24.
6. The rate of overall clinicohematologic responses (CR + PR) according to both guidelines (Barosi et al. 2009 and 2013) at month 6 and month 24.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaetsklinikum Aachen AöR

Sponsor organisation

Universitaetsklinikum Aachen AöR

Address

Pauwelsstrasse 30

City

Aachen

Postcode

52074

Country

Germany

Scientific contact point

Organisation

Universitaetsklinikum Aachen AöR

Contact name

Univ.-Prof. Dr. med. Steffen Koschmieder

Public contact point

Organisation

Universitaetsklinikum Aachen AöR

Contact name

Dr. Rainer Schuckelt

Third parties 4

Locations

1 EU/EEA country · 17 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications