Phase III study investigating the efficacy and safety of ruxolitinib in Early Myelofibrosis patients with high molecular risk mutations.

• Register: EUCTR
• Last refreshed on: 11 December 2017
• Main ID: EUCTR2014-004928-21-AT
• Date of registration: 21/12/2015
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: Phase III study investigating the efficacy and safety of ruxolitinib in Early Myelofibrosis patients with high molecular risk mutations.
• Scientific title: A randomized, double blind, placebo-controlled, multi-center, Phase III study investigating the efficacy and safety of ruxolitinib in Early Myelofibrosis patients with high molecular risk mutations
• Date of first enrolment: 29/01/2016
• Target sample size: 320
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-004928-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belgium, Brazil, Bulgaria, China, Czech Republic, Denmark, Finland, France, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Japan, Korea, Republic of, Norway, Poland, Portugal, Russian Federation, Singapore, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, United Kingdom

Contacts

• Name: Drug Regulatory Affairs
• Affiliation: Novartis Pharma GmbH

• Name: Drug Regulatory Affairs
• Affiliation: Novartis Pharma GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
Confirmed diagnosis of MF with bone marrow fibrosis of at least Grade 1; irrespective of JAK2 mutational status
Patients with at least one mutation in one of the five HMR genes (ASXL1, EZH2, SRSF2 and IDH1/2)
Patients with non-palpable spleen or spleen palpable = 5 cm from the left costal margin to the point of greatest splenic protrusion
Patients with MF-7 score of = 15, with each individual symptom score of = 3

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 128
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 192

Exclusion criteria:
Patients with prior treatment with ruxolitinib or other JAK inhibitors


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Early Myelofibrosis patients with high molecular risk mutations
MedDRA version: 18.1 Level: PT Classification code 10028537 Term: Myelofibrosis System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: Jakavi
Product Name: Ruxolitinib
Product Code: INC424
Pharmaceutical Form: Tablet
INN or Proposed INN: ruxolitinib
CAS Number: 1092939-17-7
Current Sponsor code: INC424
Other descriptive name: RUXOLITINIB PHOSPHATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Progression free survival (PFS-1) from date of randomization until the occurrence of any of the criteria for disease progression (See Section 10.4.1 for details on criteria and required confirmation):
- Progressive splenomegaly
- Circulating peripheral blast counts > 10%
- Leukemic transformation
- Hb < 10g/dl with absolute decrease of at least 3 g/dl from baseline
- White blood cell (WBC) counts > 25 x 103/ µL
- MF-7 score = 30
- Death from any cause

Main Objective: To evaluate the effect of ruxolitinib in delaying progression of MF from early disease to more advanced disease stages.

Secondary Objective: To evaluate time to disease progression of MF with or without ruxolitinib.
To evaluate the changes in spleen volume with or without ruxolitinib.
To assess the changes in symptoms using MF-7, EuroQol-5D-5L (EQ-5D).
To assess the safety and tolerability of ruxolitinib.
To evaluate the effect of ruxolitinib on overall survival.
To assess the pharmacokinetics of ruxolitinib.

To evaluate the efficacy of ruxolitinib post progression

Timepoint(s) of evaluation of this end point: Primary endpoint evaluated after 90 PFS-1 events are documented.

Secondary Outcome(s)

Secondary end point(s): Time to primary progression
Time to first progressive splenomegaly as determined by spleen volume (by MRI/CT)
Change in spleen volume (by MRI/CT) from baseline
Time to first symptomatic progression as determined by MF-7
Quality-adjusted life years using EQ-5D
Changes in symptoms using MF-7 and EQ-5D from baseline
Monitoring the frequency, duration, and severity of adverse events including abnormalities in vital signs, laboratory parameters and ECG data
Overall survival
Plasma ruxolitinib concentrations. Characterize PK by utilizing a Population PK approach
Progression free survival (PFS-2) assessed by 25% increase over new baseline of PFS-1 in any of the following (See Section 10.5.1 of the protocol for details):
- Progressive splenomegaly
- 25 % increase in MF-7 score with absolute score = 30

Timepoint(s) of evaluation of this end point: Secondary endpoint evaluated after 90 PFS-1 events are documented.

Secondary ID(s)

CINC424A2353

2014-004928-21-ES

Source(s) of Monetary Support

Novartis Pharma Services AG