A study investigating the safety and efficacy of LDE225 and INC424 in patients with myelofibrosis

Phase 1

• Conditions: myelofibrosis; MedDRA version: 18.0Level: PTClassification code 10028537Term: MyelofibrosisSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-004023-20-GB
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-04-11
• Last Update Posted: 28 May 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 82

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 counts > or = 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 may apply.
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 41
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 41

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 per day) and 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To establish the MTD and/or recommended phase II dose of the co-administration of LDE225 and INC424 in patients with MF, who have not previously received therapy with a JAK inhibitor;Secondary Objective: - To evaluate the safety of the co-administration of LDE225 and INC424 in patients with MF<br>- To characterize the single and multiple dose pharmacokinetics following the co-administration of LDE225 and INC424 <br>;Primary end point(s): Dose Limiting Toxicities (DLTs) occurring during the first 6 weeks of the co-administration of INC424 and LDE225;Timepoint(s) of evaluation of this end point: During the first 6 weeks of the co-administration of INC424 and LDE225

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Adverse and serious adverse events, abnormalities in physical examinations, vital signs and laboratory test values, including ECG data<br>- LDE225 and INC424 PK parameters <br>;Timepoint(s) of evaluation of this end point: As defined in Table 7-1 of the protocol.