A Phase Ib/II, open-label, multi-center, dose-finding study to assess the safety and efficacy of the oral combination of LDE225 and INC424 (Ruxolitinib) in patients with myelofibrosis

Completed

Conditions: Myelofibrosis
a disorder of the bone marrow
myelofibrosis
10018865

Registration Number: NL-OMON41302

Lead Sponsor: ovartis

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 5

Inclusion Criteria

- Diagnosed with PMF per 2008 WHO criteria, post-PV MF or post-ET MF per IWG-MRT criteria.
- Ineligible or unwilling to undergo stem cell transplantion.
- PLT count * 75X 10^9/L not reached with the aid of transfusions.
- ECOG performance status * 2.
- Palpable splenomegaly defined as * 5 cm below the left costal margin.
- Intermediate risk level 1 (1 prognostic factor which is not age), Intermediate risk level 2, or high risk.
- Active symptoms of MF.;Other protocol defined inclusion criteria apply, see protocol section 5.2 for more detail.

Exclusion Criteria

-Previous therapy with JAK or Smoothened inhibitors.
- Patient is currently on medications that interfere with coagulation (including warfarin) or platelet function. Low dose aspirin (up to 150 mg) and low molecular weight heparin (LMWH) are allowed.
- Impairment of GI function or GI disease that may significantly alter the absorption of INC424 or LDE225 (e.g., uncontrolled nausea, vomiting, diarrhea; malabsorption syndrome; small bowel resection).
- Splenic irradiation within 12 months prior to Screening.
- Pregnant or nursing women.
- Women of childbearing potential not using highly effective methods of contraception
- Sexually active males who refuse condom use
- Patients who have neuromuscular disorders or are on concomitant treatment with drugs that are recognized to cause rhabdomyolysis.;Other protocol defined exclusion criteria may apply, see protocol section 5.3 for more detail.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Dose Limiting Toxicities (DLTs) occurring during the first 6 weeks of the<br /><br>co-administration of INC424 and LDE225</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- Adverse and serious adverse events, abnormalities in physical examinations,<br /><br>vital signs and laboratory test values, including ECG data<br /><br>- LDE225 and INC424 PK parameters</p><br>