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

NCT ID: NCT02078609

Last Updated: 2020-12-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-20
• Study Completion Date: 2019-04-18

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.

Conditions

AML and High Risk MDS

Keywords

AML,; MDS,; PIM,; LGH447,; acute myelod leukemia,; myelodysplastic syndrome,; midostaurin,; PKC412

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

LGH447 monotherapy arm

LGH447 monotherapy in patients with AML or MDS

Group Type: EXPERIMENTAL

LGH447

Intervention Type: DRUG

LGH447 in patients with AML or MDS

LGH447 + midostaurin combination arm

LGH447 + midostaurin in patients with AML

Group Type: EXPERIMENTAL

LGH447 + midostaurin

Intervention Type: DRUG

LGH447 + midostaurin in patients with AML

Interventions

LGH447

LGH447 in patients with AML or MDS

Intervention Type: DRUG

LGH447 + midostaurin

LGH447 + midostaurin in patients with AML

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

-Male or female patients ≥18 years of age who present with one of the following:

LGH447 monotherapy arm

• Refractory/Relapsed AML following no more than 2 prior therapies, or in previously untreated AML patients who are not candidates for standard therapy.
• High and very high risk MDS according to the revised International Prognostic Scoring System (rIPSS) who have failed prior therapies, such as azacitidine and decitabine
• Patients with rIPSS score of > 4.5

LGH447 and midostaurin combination arm

• Refractory/Relapsed AML following no more than 2 prior therapies, or in previously untreated AML patients who are not candidates for standard therapy. AML patients may have either FLT3 wild type or FLT3-ITD/TKD mutant disease, and FLT3 mutation status needs to be defined at study entry.

• For AML patients, peripheral blast counts < 50,000 blasts/mm3
• For MDS patients;
• Platelet count > 25,000/mm3
• Neutrophils > 500/mm3
• Blood transfusions are allowed to maintain clinically adequate hemoglobin and hematocrit levels

• Patients with active central nervous system (CNS) disease are eligible to participate and may be treated concurrently with intrathecal (or intra Ommaya) chemotherapy
• Patients who are maintained on prophylactic antibiotics are eligible to participate as long as agents comply with the list of approved concomitant medications
• Performance status ≤ 2
• Meet other lab criteria

Exclusion Criteria

• Systemic antineoplastic therapy (including unconjugated therapeutic antibodies and toxin immunoconjugates) or any experimental therapy within 7 days or 5 half-lives, whichever is longer, before the first dose of LGH447 monotherapy or LGH447 in combination with midostaurin
• Radiotherapy with a wide field of radiation within 28 days or radiotherapy with a limited field of radiation for palliation within 7 days of the first dose of LGH447 monotherapy or LGH447 in combination with midostaurin
• Patients who received CNS irradiation for meningeal leukemia, except if radiotherapy occurred > 3 months previously
• Major surgery within 4 weeks before the first dose of LGH447 monotherapy or LGH447 in combination with midostaurin
• Ongoing therapy with corticosteroids greater than 10 mg of prednisone or its equivalent per day. Inhaled and topical steroids are permitted
• Patients who are currently receiving hydroxyurea to control peripheral blood leukemic blasts and cannot be discontinued for at least 48 hours prior to obtaining PD biomarkers at screening/baseline and during the study
• Patients who are currently receiving treatment with prohibited medication and that cannot be discontinued at least one week prior to the start of treatment with LGH447 monotherapy or LGH447 in combination with midostaurin
• Active infection requiring systemic therapy or other severe infection, including pneumonia, within 2 weeks before the first dose of LGH447 monotherapy or LGH447 in combination with midostaurin
• Known human immunodeficiency virus (HIV) positive
• Corrected QT interval (QTc) of > 450 milliseconds (ms) in males and > 470 milliseconds (ms) in females on baseline electrocardiogram (ECG) (using corrected QT interval using Fridericia [QTcF] or local standards).
• Uncontrolled cardiovascular condition, including ongoing cardiac arrhythmias, congestive heart failure, angina, or myocardial infarction within the past 6 months
• Pregnant or nursing

• 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

Ann Arbor, Michigan, United States

Novartis Investigative Site

Prahran, Victoria, Australia

Novartis Investigative Site

Marseille, , France

Novartis Investigative Site

Ulm, , Germany

Novartis Investigative Site

Milan, MI, Italy

Novartis Investigative Site

Milan, MI, Italy

Novartis Investigative Site

Roma, RM, Italy

Novartis Investigative Site

Shinagawa Ku, Tokyo, Japan

Novartis Investigative Site

Amsterdam, , Netherlands

Countries

United States; Australia; France; Germany; Italy; Japan; Netherlands

Related Links

https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17619

Results for CLGH447X2102 can be found on the Novartis Clinical Trial Results Website

Other Identifiers

2013-003756-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLGH447X2102

Identifier Type: -

Identifier Source: org_study_id