Study of the Safety and Effectiveness of LGH447 and BYL719 in Patients With Relapsed and Refractory Multiple Myeloma

NCT ID: NCT02144038

Last Updated: 2020-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-07-23

Study Completion Date

2015-10-28

Brief Summary

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This is a Phase Ib/II study with the primary purpose of the Phase Ib part being to estimate the MTD and/or recommended phase 2 dose (RP2D) of the combination of LGH447 and BYL719 when administered orally to adult patients with relapsed and refractory multiple myeloma. Once the MTD and/or RP2D is determined for the combination of LGH447 and BYL719, additional patients will be enrolled in the Phase II part to determine whether the combination of LGH447 and BYL719 exhibits improved anti-multiple myeloma activity compared to single agent LGH447. This trial never made it to the Phase II part of the this trial.

Detailed Description

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Conditions

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Relapsed and Refractory Multiple Myeloma

Keywords

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multiple myeloma, relapsed and refractory, LGH447, pan-PIM inhibitor, PIM Kinase, BYL719, PI3K inhibitor

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phase Ib: LGH447 + BYL719

Dose-escalation, LGH447 in combinatinon with BYL719

Group Type EXPERIMENTAL

LGH447

Intervention Type DRUG

pan-PIM inhibitor

BYL719

Intervention Type DRUG

PI3K-alpha inhibitor

Phase II: LGH447 + BYL719

LGH447 + BYL719 (dosing according to MTD/RP2D from Phase Ib portion of the study)

Group Type EXPERIMENTAL

LGH447

Intervention Type DRUG

pan-PIM inhibitor

BYL719

Intervention Type DRUG

PI3K-alpha inhibitor

Phase II: LGH447 alone

LGH447 alone (dosing according to single-agent RDE)

Group Type EXPERIMENTAL

LGH447

Intervention Type DRUG

pan-PIM inhibitor

Interventions

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LGH447

pan-PIM inhibitor

Intervention Type DRUG

BYL719

PI3K-alpha inhibitor

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
* For patients in the Phase II portion of the study, must have measurable disease defined by at least 1 of the following 3 measurements:

* Serum M-protein ≥ 0.5 g/dL
* Urine M-protein ≥ 200 mg/24 hours OR
* Serum free light chain (FLC) \> 100 mg/L of involved FLC
* All patients must be willing to undergo a mandatory bone marrow aspirate and/or biopsy at baseline for the assessment of biomarker/pharmacodynamics and disease status

Exclusion Criteria

* Systemic antineoplastic therapy (including unconjugated therapeutic antibodies and toxin immunoconjugates) or any experimental therapy within 14 days or 5 half-lives, whichever is shorter, before the first dose of either study drug
* Radiotherapy within 14 days before the first dose of either study drug except localized radiation therapy for lytic bone lesions and plasmacytomas
* Major surgery within 2 weeks before the first dose of either study drug
* Ongoing therapy with chronic or high dose corticosteroids. Low dose steroids (i.e. prednisone ≤ 10 mg or an equivalent steroid dose), inhaled and topical steroids are permitted
* Patients who are currently receiving treatment with a prohibited medication that cannot be discontinued at least one week prior to the start of treatment:
* Narrow Therapeutic index substrates, strong inhibitors and strong inducers of CYP3A4
* Strong Inhibitors of CYP2D6
* Narrow therapeutic index substrates of CYP2C8, CYP2C9, CYP2C19 and CYP2D6
* Any of the following clinical laboratory results during screening (i.e., within 28 days before the first dose of either study drug):
* Absolute neutrophil count (ANC) \< 1,000/mm3 without growth factor support within 7 days prior to testing
* Platelet count \< 75,000 mm3 without transfusion support within 7 days prior to testing
* Bilirubin \> 1.5 times the upper limit of the normal range (ULN).
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 3 times the ULN.
* Calculated creatinine clearance \< 30 ml/min according to Cockcroft-Gault equation
* Corrected QT interval (QTc) of \> 450 milliseconds (ms) in males and \> 470 milliseconds (ms) in females on baseline electrocardiogram (ECG) (using Fridericia \[QTcF\] corrected QT interval
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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University of Texas/MD Anderson Cancer Center Dept.ofMDAndersonCancerCtr(SC)

Houston, Texas, United States

Site Status

Seattle Cancer Care Alliance Oncology Dept

Seattle, Washington, United States

Site Status

University of Wisconsin / Paul P. Carbone Comp Cancer Center Dept of Onc.

Madison, Wisconsin, United States

Site Status

Novartis Investigative Site

Prahran, Victoria, Australia

Site Status

Novartis Investigative Site

Heidelberg, , Germany

Site Status

Novartis Investigative Site

Kiel, , Germany

Site Status

Novartis Investigative Site

Milan, MI, Italy

Site Status

Novartis Investigative Site

Singapore, , Singapore

Site Status

Countries

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Hong Kong Spain United States Australia Germany Italy Singapore

Related Links

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https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=15147

Results for CLGH447X2103C can be found on the Novartis Clinical Trial Results Website

Other Identifiers

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2013-004959-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLGH447X2103C

Identifier Type: -

Identifier Source: org_study_id