A Study of Oral LGH447 in Patients With Relapsed and/or Refractory Multiple Myeloma

Novartis Pharmaceuticals79 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Multiple Myeloma

Interventions

LGH447DRUG

midazolamDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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/exclusion criteria may apply.

Locations (8)

Novartis Investigative Site

Chicago, Illinois, United States

Novartis Investigative Site

Ann Arbor, Michigan, United States

Novartis Investigative Site

Rochester, Minnesota, United States

Novartis Investigative Site

Houston, Texas, United States

Outcomes

Primary Outcomes

Estimate the MTD and/or RDE

Incidence rate of dose limiting toxicity

Time frame: 12 months

Secondary Outcomes

Number of participants with adverse events and serious adverse events.

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.

Time frame: 18 months

Pharmacokinetic (PK) effects of LGH447

Summary of PK parameters such as AUC, Cmax,

Time frame: 18 months

Pharmacodynamic (PD) effects of LGH447

Changes between pre and post treatment levels in bone marrow aspirates and whole blood.

Time frame: 18 months

Anti-Myeloma activity associated with LGH447

Overall Response Rate (ORR), Duration of Response (DOR), and Progression Free Survival (PFS) based on International Myeloma Working Group Response Criteria.

Time frame: 18 months

Effect of multiple-doses of LGH447 on the PK of midazolam

PK parameters of midazolam and 1-hydroxymidazolam, such as AUC and Cmax, as well as metabolic ratio of midazolam.

Time frame: 6 months

Data from ClinicalTrials.gov

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