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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02078609




Registration number
NCT02078609
Ethics application status
Date submitted
31/01/2014
Date registered
5/03/2014
Date last updated
17/12/2020

Titles & IDs
Public title
A Safety and Efficacy Study of LGH447 in Patients With Acute Myeloid Leukemia (AML) or High Risk Myelodysplastic Syndrome (MDS)
Scientific title
A Phase I, Multicenter, Open-label Study of Oral LGH447 in Patients With Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome
Secondary ID [1] 0 0
2013-003756-20
Secondary ID [2] 0 0
CLGH447X2102
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
AML and High Risk MDS 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - LGH447
Treatment: Drugs - LGH447 + midostaurin

Experimental: LGH447 monotherapy arm - LGH447 monotherapy in patients with AML or MDS

Experimental: LGH447 + midostaurin combination arm - LGH447 + midostaurin in patients with AML


Treatment: Drugs: LGH447
LGH447 in patients with AML or MDS

Treatment: Drugs: LGH447 + midostaurin
LGH447 + midostaurin in patients with AML
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
28 days post study treatment
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
weekly to bi-weekly up to 1.5 years
Secondary outcome [2] 0 0
PK parameters of the LGH447 monotherapy arm in patients with AML or MDS and of the LGH447 + midostaurin treatment arm in patients with AML
Timepoint [2] 0 0
days 1, 2, 15, 16, 29, 30, 44, 57, and approximately monthly through Cycle 3
Secondary outcome [3] 0 0
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
Timepoint [3] 0 0
screening, days 1 and 29 up to 1.5 years
Secondary outcome [4] 0 0
Anti-tumor activity in AML or high risk MDS associated wtih LGH447
Timepoint [4] 0 0
Day 29 up to 1.5 years
Secondary outcome [5] 0 0
Anti-tumor activity in AML or high risk MDS associated wtih LGH447 in combination with midostaurin
Timepoint [5] 0 0
Day 29 up to 1.5 years

Eligibility
Key inclusion 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/03/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
18/04/2019
Sample size
Target
Accrual to date
Final
70
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Prahran
Recruitment postcode(s) [1] 0 0
3181 - Prahran
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Michigan
Country [2] 0 0
France
State/province [2] 0 0
Marseille
Country [3] 0 0
Germany
State/province [3] 0 0
Ulm
Country [4] 0 0
Italy
State/province [4] 0 0
MI
Country [5] 0 0
Italy
State/province [5] 0 0
RM
Country [6] 0 0
Japan
State/province [6] 0 0
Tokyo
Country [7] 0 0
Netherlands
State/province [7] 0 0
Amsterdam

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT02078609
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02078609