A Safety and Efficacy Study of LGH447 in Patients With Acute Myeloid Leukemia (AML) or High Risk Myelodysplastic Syndrome (MDS)

Phase 1

Completed

• Conditions: AML and High Risk MDS
• Interventions: Drug: LGH447; Drug: LGH447 + midostaurin

• Registration Number: NCT02078609
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

This study will assess the safety and preliminary efficacy of escalating doses of LGH447 monotherapy in AML and MDS and LGH447 in combination with midostaurin in AML.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-01-31
• Study First Submitted QC: 2014-03-03
• Study First Posted: 2014-03-05
• Study Start: 2014-03-20
• Primary Completion: 2019-04-18
• Study Completion: 2019-04-18
• Status Verified: 2020-01
• Last Update Submitted: 2020-12-16
• Last Update Posted: 2020-12-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LGH447 monotherapy arm	LGH447	LGH447 monotherapy in patients with AML or MDS
LGH447 + midostaurin combination arm	LGH447 + midostaurin	LGH447 + midostaurin in patients with AML

Primary Outcome Measures

Name	Time	Method
Incidence rate of dose limiting toxicities (DLTs) of LGH447 monotherapy arm in patients with AML or MDS and of LGH447 + midostaurin in patients with AML	28 days post study treatment	Frequency and characteristics of dose limiting toxicities

Secondary Outcome Measures

Name	Time	Method
Number of participants with the type, frequency, and severity of adverse events (AEs) as a measure of safety and tolerability of the LGH447 monotherapy arm in patients with AML or MDS and of the LGH447 + midostaurin treatment arm in patients with AML	weekly to bi-weekly up to 1.5 years	Includes changes in hematology and blood chemistry values, assessments of physical examinations, vital signs, and electrocardiograms (ECGs)
PK parameters of the LGH447 monotherapy arm in patients with AML or MDS and of the LGH447 + midostaurin treatment arm in patients with AML	days 1, 2, 15, 16, 29, 30, 44, 57, and approximately monthly through Cycle 3	LGH447 and midostaurin plasma concentrations and basic PK parameters
Changes between pre- and post-treatment levels of pS6RP and p4EBP1 in bone marrow aspirates and p4EBP1 in peripheral blood of the LGH447 monotherapy arm in patients with AML or MDS and of the LGH447 + midostaurin treatment arm in patients with AML	screening, days 1 and 29 up to 1.5 years	Assess pharmacodynamic effects of LGH447
Anti-tumor activity in AML or high risk MDS associated wtih LGH447	Day 29 up to 1.5 years	To assess any preliminary anti-tumor activity in AML or high risk MDS associated with LGH447
Anti-tumor activity in AML or high risk MDS associated wtih LGH447 in combination with midostaurin	Day 29 up to 1.5 years	To assess any preliminary anti-tumor activity in AML or high risk MDS associated with LGH447 in combination with midostaurin

Trial Locations

Locations (1)

Novartis Investigative Site; 🇳🇱 Amsterdam, Netherlands