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

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01456689
Collaborator
(none)
79
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2
85.3
9.9
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Study Details

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).

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
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 :
Apr 25, 2012
Actual Primary Completion Date :
Jun 5, 2019
Actual Study Completion Date :
Jun 5, 2019

Arms and Interventions

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

Primary Outcome Measures

  1. Estimate the MTD and/or RDE [12 months]

    Incidence rate of dose limiting toxicity

Secondary Outcome Measures

  1. 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.

  2. Pharmacokinetic (PK) effects of LGH447 [18 months]

    Summary of PK parameters such as AUC, Cmax,

  3. Pharmacodynamic (PD) effects of LGH447 [18 months]

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

  4. 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.

  5. 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts 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/exclusion criteria may apply.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Novartis Investigative Site Chicago Illinois United States 60637
2 Novartis Investigative Site Ann Arbor Michigan United States 48109
3 Novartis Investigative Site Rochester Minnesota United States 55905
4 Novartis Investigative Site Houston Texas United States 77030
5 Novartis Investigative Site Heidelberg Germany 69120
6 Novartis Investigative Site Kiel Germany 24105
7 Novartis Investigative Site Singapore Singapore 169608
8 Novartis Investigative Site Salamanca Castilla Y Leon Spain 37007

Sponsors and Collaborators

  • Novartis Pharmaceuticals

Investigators

  • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01456689
Other Study ID Numbers:
  • CLGH447X2101
  • 2011-003820-10
First Posted:
Oct 21, 2011
Last Update Posted:
Dec 17, 2020
Last Verified:
Oct 1, 2019
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:

Study Results

No Results Posted as of Dec 17, 2020