search
Back to results

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

Primary Purpose

Multiple Myeloma

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
LGH447
midazolam
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring Myeloma, Multiple Myeloma, MM

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

LGH447

LGH447 and midazolam

Arm Description

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

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.

Outcomes

Primary Outcome Measures

Estimate the MTD and/or RDE
Incidence rate of dose limiting toxicity

Secondary Outcome Measures

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.
Pharmacokinetic (PK) effects of LGH447
Summary of PK parameters such as AUC, Cmax,
Pharmacodynamic (PD) effects of LGH447
Changes between pre and post treatment levels in bone marrow aspirates and whole blood.
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.
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.

Full Information

First Posted
October 11, 2011
Last Updated
December 16, 2020
Sponsor
Novartis Pharmaceuticals
search

1. Study Identification

Unique Protocol Identification Number
NCT01456689
Brief Title
A Study of Oral LGH447 in Patients With Relapsed and/or Refractory Multiple Myeloma
Official Title
A Multi-Center, Open-Label, Dose Escalation, Phase 1 Study of Oral LGH447 in Patients With Relapsed and/or Refractory Multiple Myeloma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
April 25, 2012 (Actual)
Primary Completion Date
June 5, 2019 (Actual)
Study Completion Date
June 5, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Myeloma, Multiple Myeloma, MM

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
79 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LGH447
Arm Type
Experimental
Arm Description
Eligible patients will be treated with oral LGH447 until disease progression or occurrence of unacceptable toxicity.
Arm Title
LGH447 and midazolam
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
LGH447
Intervention Type
Drug
Intervention Name(s)
midazolam
Primary Outcome Measure Information:
Title
Estimate the MTD and/or RDE
Description
Incidence rate of dose limiting toxicity
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Number of participants with adverse events and serious adverse events.
Description
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
Title
Pharmacokinetic (PK) effects of LGH447
Description
Summary of PK parameters such as AUC, Cmax,
Time Frame
18 months
Title
Pharmacodynamic (PD) effects of LGH447
Description
Changes between pre and post treatment levels in bone marrow aspirates and whole blood.
Time Frame
18 months
Title
Anti-Myeloma activity associated with LGH447
Description
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
Title
Effect of multiple-doses of LGH447 on the PK of midazolam
Description
PK parameters of midazolam and 1-hydroxymidazolam, such as AUC and Cmax, as well as metabolic ratio of midazolam.
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Novartis Investigative Site
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Novartis Investigative Site
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Novartis Investigative Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Novartis Investigative Site
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Novartis Investigative Site
City
Kiel
ZIP/Postal Code
24105
Country
Germany
Facility Name
Novartis Investigative Site
City
Singapore
ZIP/Postal Code
169608
Country
Singapore
Facility Name
Novartis Investigative Site
City
Salamanca
State/Province
Castilla Y Leon
ZIP/Postal Code
37007
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17667
Description
Results for CLGH447X2101 can be found on the Novartis Clinical Trial Results Website

Learn more about this trial

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

We'll reach out to this number within 24 hrs