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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02144038




Registration number
NCT02144038
Ethics application status
Date submitted
1/05/2014
Date registered
21/05/2014
Date last updated
17/12/2020

Titles & IDs
Public title
Study of the Safety and Effectiveness of LGH447 and BYL719 in Patients With Relapsed and Refractory Multiple Myeloma
Scientific title
A Phase Ib/II, Multi-center, Study of Oral LGH447 in Combination With Oral BYL719 in Patients With Relapsed and Refractory Multiple Myeloma
Secondary ID [1] 0 0
2013-004959-21
Secondary ID [2] 0 0
CLGH447X2103C
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsed and Refractory Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - LGH447
Treatment: Drugs - BYL719

Experimental: Phase Ib: LGH447 + BYL719 - Dose-escalation, LGH447 in combinatinon with BYL719

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

Experimental: Phase II: LGH447 alone - LGH447 alone (dosing according to single-agent RDE)


Treatment: Drugs: LGH447
pan-PIM inhibitor

Treatment: Drugs: BYL719
PI3K-alpha inhibitor
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase Ib: Number of Total Dose-limiting Toxicities (DLT)
Timepoint [1] 0 0
Cycle 1 (28 days)
Primary outcome [2] 0 0
Phase II: Overall Response Rate (ORR) as assessed by Investigators
Timepoint [2] 0 0
29 months (End of Study)
Secondary outcome [1] 0 0
Phase II: Percent change of ORR (Overall Response Rate) between the two arms
Timepoint [1] 0 0
29 months (End of Study)
Secondary outcome [2] 0 0
Number of participants with adverse events, serious adverse events, changes in laboratory values, and electrocardiograms (ECGs), as a measure of safety and tolerability.
Timepoint [2] 0 0
23 months
Secondary outcome [3] 0 0
Determine single and multiple dose Pharmacokinetics (PK) profiles
Timepoint [3] 0 0
Approximately 8 months
Secondary outcome [4] 0 0
Changes between pre- and post-treatment levels of pS6RP and 4EBP1 levels in bone marrow aspirates and 4EBP1 in peripheral blood
Timepoint [4] 0 0
baseline, Cycle 2 Day 1
Secondary outcome [5] 0 0
Phase II: Absolute difference in ORR
Timepoint [5] 0 0
29 months (End of Study)
Secondary outcome [6] 0 0
Disease Control Rate
Timepoint [6] 0 0
29 months (End of Study)
Secondary outcome [7] 0 0
Progression Free Survival
Timepoint [7] 0 0
29 months (End of Study)
Secondary outcome [8] 0 0
Time to response
Timepoint [8] 0 0
29 months (End of Study)
Secondary outcome [9] 0 0
Duration of Response
Timepoint [9] 0 0
29 months (End of Study)

Eligibility
Key inclusion criteria
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2

- Patients with a confirmed diagnosis of multiple myeloma who have received two or more
lines of therapy and are refractory to their most recent line of therapy, as defined
as relapse while on therapy or within 60 days from their last line of therapy. If
patient has not received either an immunomodulatory drug (IMID) or proteasome
inhibitor as a prior therapy then Investigator must notify Novartis prior to the
patient enrollment. Patients who have received a prior bone marrow transplant and
otherwise meet the inclusion criteria are eligible for this study

- 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
23/07/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
28/10/2015
Sample size
Target
Accrual to date
Final
20
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Prahran
Recruitment postcode(s) [1] 0 0
3181 - Prahran
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Texas
Country [2] 0 0
United States of America
State/province [2] 0 0
Washington
Country [3] 0 0
United States of America
State/province [3] 0 0
Wisconsin
Country [4] 0 0
Germany
State/province [4] 0 0
Heidelberg
Country [5] 0 0
Germany
State/province [5] 0 0
Kiel
Country [6] 0 0
Italy
State/province [6] 0 0
MI
Country [7] 0 0
Singapore
State/province [7] 0 0
Singapore

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02144038
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02144038