Multiple Myeloma
Conditions
Keywords
Myeloma, Multiple Myeloma, MM
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).
Interventions
DRUGLGH447
DRUGmidazolam
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of multiple myeloma that is relapsed and/or refractory for which no curative option exists. * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2. * 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
Exclusion criteria
* 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Estimate the MTD and/or RDE | 12 months | Incidence rate of dose limiting toxicity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
Countries
Germany, Singapore, Spain, United States
Outcome results
None listed