AML and High Risk MDSPhase 1NCT02078609
A Safety and Efficacy Study of LGH447 in Patients With Acute Myeloid Leukemia (AML) or High Risk Myelodysplastic Syndrome (MDS)
A Phase 1 study testing LGH447 and LGH447 + midostaurin in people with AML and High Risk MDS, run by Novartis Pharmaceuticals at 9 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- AML and High Risk MDS
- What is being tested?
- LGH447 and LGH447 + midostaurin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 9 sitesin 7 countries
- Study dates
- 20 Mar 2014to 18 Apr 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- -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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
9 sites in 7 countries.
9 sites in 7 countries
Italy3 sites
Novartis Investigative Site
Milan, MI, 20132
Novartis Investigative Site
Milan, MI, 20162
Novartis Investigative Site
Roma, RM, 00133
United States1 site
Novartis Investigative Site
Ann Arbor, Michigan, 48109
About this study
Official title: A Phase I, Multicenter, Open-label Study of Oral LGH447 in Patients With Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome
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
- Being tested
- LGH447, LGH447 + midostaurin
- Keywords
- AML,, MDS,, PIM,, LGH447,, acute myelod leukemia,, myelodysplastic syndrome,, midostaurin,, PKC412
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LGH447Drug
LGH447 in patients with AML or MDS
LGH447 + midostaurinDrug
LGH447 + midostaurin in patients with AML
| Study group | Role | What they receive |
|---|---|---|
| LGH447 monotherapy arm | Experimental | LGH447 monotherapy in patients with AML or MDS Receives: Drug: LGH447 |
| LGH447 + midostaurin combination arm | Experimental | LGH447 + midostaurin in patients with AML Receives: Drug: LGH447 + midostaurin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Frequency and characteristics of dose limiting toxicities
Measured: 28 days post study treatment
Secondary outcomes (5)
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
Includes changes in hematology and blood chemistry values, assessments of physical examinations, vital signs, and electrocardiograms (ECGs)
Measured: weekly to bi-weekly up to 1.5 years
PK parameters of the LGH447 monotherapy arm in patients with AML or MDS and of the LGH447 + midostaurin treatment arm in patients with AML
LGH447 and midostaurin plasma concentrations and basic PK parameters
Measured: days 1, 2, 15, 16, 29, 30, 44, 57, and approximately monthly through Cycle 3
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
Assess pharmacodynamic effects of LGH447
Measured: screening, days 1 and 29 up to 1.5 years
Anti-tumor activity in AML or high risk MDS associated wtih LGH447
To assess any preliminary anti-tumor activity in AML or high risk MDS associated with LGH447
Measured: Day 29 up to 1.5 years
Anti-tumor activity in AML or high risk MDS associated wtih LGH447 in combination with midostaurin
To assess any preliminary anti-tumor activity in AML or high risk MDS associated with LGH447 in combination with midostaurin
Measured: Day 29 up to 1.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2014 (estimated)
- Study start20 Mar 2014
- Primary completion18 Apr 2019
- Study completion18 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AML and High Risk MDSStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02078609
- Sponsor's protocol ID
- CLGH447X2102
- Other IDs
- 2013-003756-20
- Status last verified
- Jan 2020
- First submitted
- 31 Jan 2014
- Last updated
- 17 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Multicenter, Open-label Study of Oral LGH447 in Patients With Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome
- ClinicalTrials.gov ID
- NCT02078609
- Acronym / sponsor ID
- CLGH447X2102
- Conditions
- AML and High Risk MDS
- Keywords
- AML,, MDS,, PIM,, LGH447,, acute myelod leukemia,, myelodysplastic syndrome,, midostaurin,, PKC412
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 20 Mar 2014 (actual)
- Primary completion
- 18 Apr 2019 (actual)
- Study completion
- 18 Apr 2019 (actual)
- First posted
- 5 Mar 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LGH447 monotherapy arm | Experimental | Drug: LGH447LGH447 monotherapy in patients with AML or MDS |
| LGH447 + midostaurin combination arm | Experimental | Drug: LGH447 + midostaurinLGH447 + midostaurin in patients with AML |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LGH447LGH447 in patients with AML or MDS | Drug | LGH447 monotherapy arm |
| LGH447 + midostaurinLGH447 + midostaurin in patients with AML | Drug | LGH447 + midostaurin combination arm |
Primary outcome
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
Time frame: 28 days post study treatment
Frequency and characteristics of dose limiting toxicities
5 secondary outcomes
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
Time frame: weekly to bi-weekly up to 1.5 years
PK parameters of the LGH447 monotherapy arm in patients with AML or MDS and of the LGH447 + midostaurin treatment arm in patients with AML
Time frame: days 1, 2, 15, 16, 29, 30, 44, 57, and approximately monthly through Cycle 3
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
Time frame: screening, days 1 and 29 up to 1.5 years
Anti-tumor activity in AML or high risk MDS associated wtih LGH447
Time frame: Day 29 up to 1.5 years
Anti-tumor activity in AML or high risk MDS associated wtih LGH447 in combination with midostaurin
Time frame: Day 29 up to 1.5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2020.
- Results for CLGH447X2102 can be found on the Novartis Clinical Trial Results WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
9 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LGH447 and LGH447 + midostaurin in people with AML and High Risk MDS, run by Novartis Pharmaceuticals at 9 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Italy, United States, Australia, France, Germany and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: 28 days post study treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2020.