Dose Escalation Study of LGH447 in Japanese Patients With Relapsed and/or Refractory Hematologic Malignancies

Study Overview
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Brief Summary
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This is a multi-center, open-label, dose escalation, Phase 1 study of oral LGH447 in Japanese patients with relapsed and/or refractory multiple myeloma for which no standard effective treatment options exist. The study consists of a dose escalation part to estimate the maximum tolerated dose and/or the recommended dose for expansion and a dose expansion part to further assess safety and preliminary anti-cancer activity of LGH447 at the maximum tolerated dose and/or the recommended dose for expansion.

Official Title
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A Multi-center, Open-label, Dose Escalation, Phase 1 Study of Oral LGH447 in Japanese Patients With Relapsed and/or Refractory Hematologic Malignancies

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: LGH447


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: -Confirmed diagnosis of relapsed and/or refractory MM for which no standard effective treatment options exist. Exclusion Criteria: -Uncontrolled cardiovascular condition, including ongoing cardiac arrhythmias, congestive heart failure, angina, or myocardial infarction within the past 6 months.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LGH447<br>LGH447, QD | Drug: LGH447<br>* LGH447, QD<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence rate of dose limiting toxicities | Estimate the maximum tolerated dose and/or recommended dose for expansion of LGH447 in Japanese patients | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with adverse events as a measure of safety and tolerability of LGH447 | Adverse events, serious adverse events, changes in laboratory values, and electrocardiograms | 28 days and till the end of the study, an average of 84 days | 
| Pharmacokinetics profile of LGH447 and its metabolites if appropriate | PK parameters such as AUC, Cmax, Tmax, T1/2. Cycle = 28 days | Baseline, 0.5, 1, 2, 3, 4, 5, 6, 8, 24 hours on Cycle1Day1, 14 and 28 and baseline on Cycle2Day14 and Cycle3Day1 | 
| Overall Response Rate | Describe any preliminary anti-cancer activity associated with LGH447 based on International Myeloma Working group Criteria with modification. | Every 28 days till the end of the study, an average of 84 days | 
| Disease control rate | Describe any preliminary anti-cancer activity associated with LGH447 based on International Myeloma Working group Criteria with modification. | Every 28 days till the end of the study, an average of 84 days | 
| Clinical benefit rate | Describe any preliminary anti-cancer activity associated with LGH447 based on International Myeloma Working group Criteria with modification. | Every 28 days till the end of the study, an average of 84 days | 
| Duration of Response | Describe any preliminary anti-cancer activity associated with LGH447 based on International Myeloma Working group Criteria with modification. | Every 28 days till the end of the study, an average of 84 days, from the first documented onset of confirmed PR or better response to the date of documented disease progression/relapse or death due to multiple myeloma | 
| Progression Free Survival | Describe any preliminary anti-cancer activity associated with LGH447 based on International Myeloma Working group Criteria with modification. | Every 28 days till the end of the study, an average of 84 days, from start of treatment to the date of event defined as the first documented disease progression/relapse, or death due to any cause | 
| Time to response | Describe any preliminary anti-cancer activity associated with LGH447 based on International Myeloma Working group Criteria with modification. | Every 28 days till the end of the study, an average of 84 days, from start of treatment until first documented best overall response | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Myeloma,, Phase I,, PIM,, Japanese patients,, LGH447