A Phase Ib/II Dose-finding Study to Assess the Safety and Efficacy of LDE225 + INC424 in Patients With MF

NCT ID: NCT01787552

Last Updated: 2020-04-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-05-08
• Study Completion Date: 2018-04-10

Brief Summary

The purpose of this phase Ib/II clinical trial was to: a) evaluate the safety of the co-administration of LDE225 and INC424 in myelofibrosis patients and establish a maximum tolerated dose and/or Recommended Phase II dose of the combination and b) to assess the efficacy of the co-administration of LDE225 and INC424 on spleen volume reduction.

Detailed Description

The study is considered to have been completed because the participants completed the study as per study design at the time of trial termination. If participants were already in extension phase until discontinuation criteria were met or alternative setting was available, they were considered as completed. The study was terminated due to one of the compounds being divested.

Conditions

Primary Myelofibrosis; Thrombocytosis; Essential Thrombocythemia; Polycythemia Vera; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Blood Coagulation Disorders; Blood Platelet Disorders; Hemorrhagic Disorders

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

LDE225 + INC424

LDE225 and INC424 in combination

Group Type: EXPERIMENTAL

LDE225

Intervention Type: DRUG

INC424

Intervention Type: DRUG

Interventions

LDE225

Intervention Type: DRUG

INC424

Intervention Type: DRUG

Eligibility Criteria

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 as demonstrated by one symptom score of at least 5 (0 to10 point scale) or two symptom scores of at least 3 (0 to 10 point scale) on the MF Symptom Assessment Form (MFSAF).

Exclusion Criteria

• Previous therapy with JAK or Smoothened inhibitors.
• Patient is currently on medications that interfere with coagulation (including warfarin) or platelet function with the exception of low dose aspirin (up to 100 mg) and LMWH.
• 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.
• WOCBP not using highly effective methods of contraception
• Sexually active males who refuse condom use
• Patients who have neuromuscular disorders (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy) or are on concomitant treatment with drugs that are recognized to cause rhabdomyolysis, such as HMG CoA inhibitors (statins), clofibrate and gemfibrozil. Pravastatin may be used if necessary, with extra caution.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Camperdown, New South Wales, Australia

Novartis Investigative Site

Woolloongabba, Queensland, Australia

Novartis Investigative Site

Leuven, , Belgium

Novartis Investigative Site

Toronto, Ontario, Canada

Novartis Investigative Site

Montreal, Quebec, Canada

Novartis Investigative Site

Roskilde, , Denmark

Novartis Investigative Site

Marseille, , France

Novartis Investigative Site

Aachen, , Germany

Novartis Investigative Site

Magdeburg, , Germany

Novartis Investigative Site

Galway, , Ireland

Novartis Investigative Site

Florence, FI, Italy

Novartis Investigative Site

Reggio Calabria, RC, Italy

Novartis Investigative Site

Amsterdam, , Netherlands

Novartis Investigative Site

Rotterdam, , Netherlands

Novartis Investigative Site

Barcelona, Catalonia, Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Glasgow, Scotland, United Kingdom

Novartis Investigative Site

London, , United Kingdom

Countries

Australia; Belgium; Canada; Denmark; France; Germany; Ireland; Italy; Netherlands; Spain; United Kingdom

References

Gupta V, Wolleschak D, Hasselbalch H, Vannucchi AM, Koschmieder S, Cervantes F, Li Y, Dong T, Wroclawska M, Bharathy S, Harrison C. Safety and efficacy of the combination of sonidegib and ruxolitinib in myelofibrosis: a phase 1b/2 dose-finding study. Blood Adv. 2020 Jul 14;4(13):3063-3071. doi: 10.1182/bloodadvances.2019001212.

Reference Type: DERIVED

PMID: 32634234 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

2012-004023-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLDE225X2116

Identifier Type: -

Identifier Source: org_study_id