A Study of Oral LGH447 in Patients With Relapsed and/or Refractory Multiple Myeloma
- Registration Number
- NCT01456689
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
The primary purpose of this dose escalation study is to estimate the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of LGH447 as a single agent when administered orally once daily to adult patients with Multiple Myeloma (MM).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 79
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Confirmed diagnosis of multiple myeloma that is relapsed and/or refractory for which no curative option exists.
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Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
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During the dose expansion part of the study patients must have measurable disease defined by at least 1 of the following 2 measurements:
- Serum M-protein ≥ 0.5 g/dL
- Urine M-protein ≥ 200 mg/24 hours
- Serum free light chain (FLC) > 100 mg/L of involved FLC
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Patients who are currently receiving treatment with medications that meet one of the following criteria and that cannot be discontinued at least one week prior to the start of treatment with LGH447:
- Strong inhibitors or inducers of CYP3A4
- CYP3A4 substrates with narrow therapeutic index
Other protocol-defined inclusion/exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description LGH447 and midazolam LGH447 Eligible patients will receive midazolam on two separate days, the first dose will be administered prior to the start of LGH447 and the second will be co-administered with LGH447. After that, the patients will continue to be treated with oral LGH447 until disease progression or occurrence of unacceptable toxicity. LGH447 LGH447 Eligible patients will be treated with oral LGH447 until disease progression or occurrence of unacceptable toxicity. LGH447 and midazolam midazolam Eligible patients will receive midazolam on two separate days, the first dose will be administered prior to the start of LGH447 and the second will be co-administered with LGH447. After that, the patients will continue to be treated with oral LGH447 until disease progression or occurrence of unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Estimate the MTD and/or RDE 12 months Incidence rate of dose limiting toxicity
- Secondary Outcome Measures
Name Time Method Number of participants with adverse events and serious adverse events. 18 months Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
Anti-Myeloma activity associated with LGH447 18 months Overall Response Rate (ORR), Duration of Response (DOR), and Progression Free Survival (PFS) based on International Myeloma Working Group Response Criteria.
Pharmacokinetic (PK) effects of LGH447 18 months Summary of PK parameters such as AUC, Cmax,
Pharmacodynamic (PD) effects of LGH447 18 months Changes between pre and post treatment levels in bone marrow aspirates and whole blood.
Effect of multiple-doses of LGH447 on the PK of midazolam 6 months PK parameters of midazolam and 1-hydroxymidazolam, such as AUC and Cmax, as well as metabolic ratio of midazolam.
Trial Locations
- Locations (1)
Novartis Investigative Site
🇪🇸Salamanca, Castilla Y Leon, Spain