NCT01456689

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).

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
79

participants targeted

Target at P75+ for phase_1 multiple-myeloma

Timeline
Completed

Started Apr 2012

Longer than P75 for phase_1 multiple-myeloma

Geographic Reach
4 countries

8 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 11, 2011

Completed
10 days until next milestone

First Posted

Study publicly available on registry

October 21, 2011

Completed
6 months until next milestone

Study Start

First participant enrolled

April 25, 2012

Completed
7.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 5, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 5, 2019

Completed
Last Updated

December 17, 2020

Status Verified

October 1, 2019

Enrollment Period

7.1 years

First QC Date

October 11, 2011

Last Update Submit

December 16, 2020

Conditions

Multiple Myeloma

Keywords

MyelomaMultiple MyelomaMM

Outcome Measures

Primary Outcomes (1)

  • Estimate the MTD and/or RDE

    Incidence rate of dose limiting toxicity

    12 months

Secondary Outcomes (5)

  • Number of participants with adverse events and serious adverse events.

    18 months

  • Pharmacokinetic (PK) effects of LGH447

    18 months

  • Pharmacodynamic (PD) effects of LGH447

    18 months

  • Anti-Myeloma activity associated with LGH447

    18 months

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

    6 months

Study Arms (2)

LGH447

EXPERIMENTAL

Eligible patients will be treated with oral LGH447 until disease progression or occurrence of unacceptable toxicity.

Drug: LGH447

LGH447 and midazolam

EXPERIMENTAL

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.

Drug: LGH447Drug: midazolam

Interventions

LGH447DRUG
LGH447LGH447 and midazolam
midazolamDRUG
LGH447 and midazolam

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

Novartis Investigative Site

Chicago, Illinois, 60637, United States

Location

Novartis Investigative Site

Ann Arbor, Michigan, 48109, United States

Location

Novartis Investigative Site

Rochester, Minnesota, 55905, United States

Location

Novartis Investigative Site

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

Heidelberg, 69120, Germany

Location

Novartis Investigative Site

Kiel, 24105, Germany

Location

Novartis Investigative Site

Singapore, 169608, Singapore

Location

Novartis Investigative Site

Salamanca, Castille and León, 37007, Spain

Location

Related Links

MeSH Terms

Conditions

Multiple MyelomaNeoplasms, Plasma Cell

Interventions

LGH-447Midazolam

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHematologic DiseasesHemic and Lymphatic DiseasesHemorrhagic DisordersLymphoproliferative DisordersImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

BenzodiazepinesBenzazepinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Novartis Pharmaceuticals

    Novartis Pharmaceuticals

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 11, 2011

First Posted

October 21, 2011

Study Start

April 25, 2012

Primary Completion

June 5, 2019

Study Completion

June 5, 2019

Last Updated

December 17, 2020

Record last verified: 2019-10

Data Sharing

IPD Sharing
Will not share

Locations

ES(1)DE(2)SG(1)US(4)