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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01456689
Recruitment Status : Completed
First Posted : October 21, 2011
Last Update Posted : December 17, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Description
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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).

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: LGH447 Drug: midazolam Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 79 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multi-Center, Open-Label, Dose Escalation, Phase 1 Study of Oral LGH447 in Patients With Relapsed and/or Refractory Multiple Myeloma
Actual Study Start Date : April 25, 2012
Actual Primary Completion Date : June 5, 2019
Actual Study Completion Date : June 5, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arms and Interventions
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Arm Intervention/treatment
Experimental: LGH447
Eligible patients will be treated with oral LGH447 until disease progression or occurrence of unacceptable toxicity.
 Drug: LGH447
Experimental: LGH447 and 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.
 Drug: LGH447
Drug: midazolam


Outcome Measures
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Primary Outcome Measures :
  1. Estimate the MTD and/or RDE [ Time Frame: 12 months ]
    Incidence rate of dose limiting toxicity


Secondary Outcome Measures :
  1. Number of participants with adverse events and serious adverse events. [ Time Frame: 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.

  2. Pharmacokinetic (PK) effects of LGH447 [ Time Frame: 18 months ]
    Summary of PK parameters such as AUC, Cmax,

  3. Pharmacodynamic (PD) effects of LGH447 [ Time Frame: 18 months ]
    Changes between pre and post treatment levels in bone marrow aspirates and whole blood.

  4. Anti-Myeloma activity associated with LGH447 [ Time Frame: 18 months ]
    Overall Response Rate (ORR), Duration of Response (DOR), and Progression Free Survival (PFS) based on International Myeloma Working Group Response Criteria.

  5. Effect of multiple-doses of LGH447 on the PK of midazolam [ Time Frame: 6 months ]
    PK parameters of midazolam and 1-hydroxymidazolam, such as AUC and Cmax, as well as metabolic ratio of midazolam.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01456689


Locations
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United States, Illinois
Novartis Investigative Site
Chicago, Illinois, United States, 60637
United States, Michigan
Novartis Investigative Site
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
Novartis Investigative Site
Rochester, Minnesota, United States, 55905
United States, Texas
Novartis Investigative Site
Houston, Texas, United States, 77030
Germany
Novartis Investigative Site
Heidelberg, Germany, 69120
Novartis Investigative Site
Kiel, Germany, 24105
Singapore
Novartis Investigative Site
Singapore, Singapore, 169608
Spain
Novartis Investigative Site
Salamanca, Castilla Y Leon, Spain, 37007
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
More Information
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Additional Information:

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01456689    
Other Study ID Numbers: CLGH447X2101
2011-003820-10 ( EudraCT Number )
First Posted: October 21, 2011    Key Record Dates
Last Update Posted: December 17, 2020
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Myeloma
Multiple Myeloma
MM
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Midazolam
 Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action