Overview

This trial is active, not recruiting.

Condition myelofibrosis
Treatments inc424/incb018424, best available therapy (bat)
Phase phase 3
Sponsor Novartis Pharmaceuticals
Start date July 2009
End date January 2011
Trial size 219 participants
Trial identifier NCT00934544, CINC424A2352, CINCB 18424-352

Summary

This is an open label, randomized study comparing the efficacy and safety of randomized 2:1 INC424/INCB018424 tablets versus best-available therapy, as selected by the investigator. The purpose is to compare the efficacy, safety and tolerability of INC424/INCB018424 given twice daily to the best-available therapy, in subjects with primary myelofibrosis (PMF), post polycythemia vera myelofibrosis (PPV-MF) or post essential thrombocythemia myelofibrosis (PET-MF).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Starting dose of 15 mg BID or 20 mg BID were selected with starting dose based on baseline platelet count. Dose titration ranging from 5 mg BID to a maximum dose of 25 mg BID was permitted during the study based on safety and efficacy. Tablets were to be taken 12 hours apart. Administration instructions were provided at study visits.
inc424/incb018424
Oral 5 mg tablets with packaged as 60-count in high-density polyethylene bottles.
(Active Comparator)
Best-available Investigator-selected therapy included a combination of available agents to treat the disease and/or its symptoms, and was selected by the investigator for each subject. Therapy changed at different times during the treatment phase. No experimental agents (e.g. those not approved for the treatment of any indication) were allowed. BAT also included the option of no treatment.
best available therapy (bat)
Best available investigator-selected therapy (oral or parenteral therapies) was commercially available and was administered according to manufacturer's instructions and investigator discretion. Instructions for prescribing and taking these therapies were found in their respective package inserts.

Primary Outcomes

Measure
Percentage of Participants With at Least 35% Reduction in Spleen Volume From Baseline at Week 48
time frame: Baseline, Week 48

Secondary Outcomes

Measure
Percentage of Participants With at Least 35% Reduction in Spleen Volume From Baseline at Week 24
time frame: Baseline, Week 24
Duration of Maintenance of at Least 35% Reduction in Spleen Volume (DoMSR) From Baseline
time frame: Baseline, every 12 weeks until 25% progression from baseline
Time to First at Least 35% Reduction in Spleen Volume From Baseline by Treatment
time frame: Baseline, every 12 weeks until first 35% reduction in spleen is achieved
Progression Free Survival (PFS) by Treatment
time frame: every three months after EOS until end of extension phase (96 weeks LPLV for the primary endpoint)
Leukemia-free Survival (LFS)
time frame: every three months after EOS until end of extension phase (96 weeks LPLV for the primary end)
Overall Survival (OS) by Treatment
time frame: every three months after EOS until end of extension phase (96 weeks LPLV for the primary end)
Percentage of Participants With Bone Marrow Histomorphology at Week 48
time frame: 48 weeks

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Subjects must be diagnosed with PMF, PPV-MF or PET-MF according to the 2008 World Health Organization criteria - Subjects with MF requiring therapy must be classified as high risk OR intermediate risk level 2 according to the prognostic factors defined by the International Working Group - Subjects with an ECOG performance status of 0, 1, 2 or 3 - Subjects with peripheral blood blast count of < 10%. - Subjects who have not previously received treatment with a JAK inhibitor Exclusion Criteria: - Subjects with a life expectancy of less than 6 months - Subjects with inadequate bone marrow reserve as demonstrated by specific clinical laboratory counts - Subjects with any history of platelet counts < 50,000/µL or ANC < 500/µL except during treatment for a myeloproliferative disorder or treatment with cytotoxic therapy for any other reason - Subjects with inadequate liver or renal function - Subjects with clinically significant bacterial, fungal, parasitic or viral infection which require therapy - Subjects with an active malignancy over the previous 5 years except specific skin cancers - Subjects with severe cardiac conditions - Subjects who have had splenic irradiation within 12 months

Additional Information

Official title A Randomized Study of INC424 (INCB018424) Tablets Compared to Best Available Therapy in Subjects With Primary Myelofibrosis, Post-Polycythemia Vera-Myelofibrosis or Post-Essential Thrombocythemia Myelofibrosis
Description Male or female individuals, aged 18 years or older who have been diagnosed with Myelofibrosis (either Primary Myelofibrosis (PMF) or Post-Polycythemia Vera Myelofibrosis (PPV-MF) or Post-Essential Thrombocythemia Myelofibrosis (PET-MF), were observed to have palpable splenomegaly, were not candidates for stem cell transplantation, and had 2 or more risk factors, thereby placing them in an intermediate-2 or high-risk prognostic group may enroll. Subjects were permitted to have received any or no prior therapy for MF. This is an open label, randomized study comparing the efficacy and safety of INCB018424 tablets versus best-available therapy, as selected by the investigator. The purpose is to compare the efficacy, safety and tolerability of INCB018424 given twice daily to the best-available therapy, in subjects with primary myelofibrosis (PMF), post polycythemia vera myelofibrosis (PPV-MF) or post essential thrombocythemia myelofibrosis (PET-MF).
Trial information was received from ClinicalTrials.gov and was last updated in April 2014.
Information provided to ClinicalTrials.gov by Novartis.