Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.
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 endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/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
Query!
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
Query!
Secondary ID [1]
0
0
2013-004959-21
Query!
Secondary ID [2]
0
0
CLGH447X2103C
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Relapsed and Refractory Multiple Myeloma
0
0
Query!
Condition category
Condition code
Cancer
0
0
0
0
Query!
Other cancer types
Query!
Intervention/exposure
Study type
Interventional
Query!
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
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Phase Ib: Number of Total Dose-limiting Toxicities (DLT)
Query!
Assessment method [1]
0
0
Using a Bayesian logistic regression model (BLRM) to guide dose escalation and predict MTD or determine the RP2D for LGH447 in combination with BYL719 in relapsed and refractory multiple myeloma. The frequency and characteristics of DLTs will be assessed.
Query!
Timepoint [1]
0
0
Cycle 1 (28 days)
Query!
Primary outcome [2]
0
0
Phase II: Overall Response Rate (ORR) as assessed by Investigators
Query!
Assessment method [2]
0
0
The proportion of patients with a confirmed best overall response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) as assessed by Investigators using the International Myeloma Working group (IMWG) Criteria with modifications.
End of Study (defined as the time when all patients have completed at least 6 cycles of treatment or discontinued treatment, or have been lost to follow up, whichever occurs first.
Query!
Timepoint [2]
0
0
29 months (End of Study)
Query!
Secondary outcome [1]
0
0
Phase II: Percent change of ORR (Overall Response Rate) between the two arms
Query!
Assessment method [1]
0
0
The ORR percent change between the two arms, LGH447 in combination with BYL719 and LGH447 alone, is the parameter of interest. Both observed and Bayesian estimates of ORR percent change along with 80% confidence intervals and credible intervals will be calculated. End of Study (defined as the time when all patients have completed at least 6 cycles of treatment or discontinued treatment, or have been lost to follow up, whichever occurs first.
Query!
Timepoint [1]
0
0
29 months (End of Study)
Query!
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.
Query!
Assessment method [2]
0
0
Assessments consisted of recording all adverse events (AEs) and serious adverse events (SAEs), the regular monitoring of hematology, blood chemistry, urinalysis, and coagulation parameters, as well as electrocardiograms.
Query!
Timepoint [2]
0
0
23 months
Query!
Secondary outcome [3]
0
0
Determine single and multiple dose Pharmacokinetics (PK) profiles
Query!
Assessment method [3]
0
0
To determine the single and multiple dose PK profiles of the LGH447 and BYL719 combination (Phase Ib and II) and LGH447 alone (Phase II), by measuring plasma concentrations of LGH447 and BYL719 respectively at different timepoints prior and post study drug combination dosing on several days within cycle 1 and subsequent cycles for all patients in the Phase 1b and for the first 15 patients in each arm in the Phase 2 portion of the study. PK parameters including but not limited to Cmax, AUCinf, AUClast, AUCtau,T1/2, Tmax, Racc, CL/F, and Vz/F
Query!
Timepoint [3]
0
0
Approximately 8 months
Query!
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
Query!
Assessment method [4]
0
0
Cycle 2 = 28 days; LGH447-mediated target modulation of the PIM pathway will be assessed from the collection of bone marrow biopsy and/or aspirates by flow cytometry, immunohistochemistry, or other methods as deemed appropriate. Decreases in the phosphorylation of markers (eg. S6RP and 4EBP1) will be measured in both pre- and post-dose bone marrow aspirate samples and peripheral blood samples.
Query!
Timepoint [4]
0
0
baseline, Cycle 2 Day 1
Query!
Secondary outcome [5]
0
0
Phase II: Absolute difference in ORR
Query!
Assessment method [5]
0
0
Both observed and Bayesian estimates of absolute difference in ORR between the two arms will be calculated. The 80% confidence intervals and credible intervals for the difference will be provided. End of Study (defined as the time when all patients have completed at least 6 cycles of treatment or discontinued treatment, or have been lost to follow up, whichever occurs first.
Query!
Timepoint [5]
0
0
29 months (End of Study)
Query!
Secondary outcome [6]
0
0
Disease Control Rate
Query!
Assessment method [6]
0
0
Proportion of patients with a best overall response of sCR, CR, VGPR, PR, MR, or SD, using International Myeloma Working Group Criteria with modification. End of Study (defined as the time when all patients have completed at least 6 cycles of treatment or discontinued treatment, or have been lost to follow up, whichever occurs first.
Query!
Timepoint [6]
0
0
29 months (End of Study)
Query!
Secondary outcome [7]
0
0
Progression Free Survival
Query!
Assessment method [7]
0
0
Defined as the time from start of treatment to the date of event defined as the first documented PD/relapse, or death due to any cause, whichever comes first. End of Study (defined as the time when all patients have completed at least 6 cycles of treatment or discontinued treatment, or have been lost to follow up, whichever occurs first.
Query!
Timepoint [7]
0
0
29 months (End of Study)
Query!
Secondary outcome [8]
0
0
Time to response
Query!
Assessment method [8]
0
0
The time between date of randomization until first documented best overall response (sCR, CR, VPGR or PR). End of Study (defined as the time when all patients have completed at least 6 cycles of treatment or discontinued treatment, or have been lost to follow up, whichever occurs first.
Query!
Timepoint [8]
0
0
29 months (End of Study)
Query!
Secondary outcome [9]
0
0
Duration of Response
Query!
Assessment method [9]
0
0
Defined as the duration from the first documented onset of PR or better response to the date of documented PD/relapse or death due to multiple myeloma. End of Study (defined as the time when all patients have completed at least 6 cycles of treatment or discontinued treatment, or have been lost to follow up, whichever occurs first.
Query!
Timepoint [9]
0
0
29 months (End of Study)
Query!
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
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
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
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Non-randomised trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 1
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Completed
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
23/07/2014
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
28/10/2015
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
20
Query!
Recruitment in Australia
Recruitment state(s)
VIC
Query!
Recruitment hospital [1]
0
0
Novartis Investigative Site - Prahran
Query!
Recruitment postcode(s) [1]
0
0
3181 - Prahran
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
Texas
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
Washington
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
Wisconsin
Query!
Country [4]
0
0
Germany
Query!
State/province [4]
0
0
Heidelberg
Query!
Country [5]
0
0
Germany
Query!
State/province [5]
0
0
Kiel
Query!
Country [6]
0
0
Italy
Query!
State/province [6]
0
0
MI
Query!
Country [7]
0
0
Singapore
Query!
State/province [7]
0
0
Singapore
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Query!
Name
Novartis Pharmaceuticals
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
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.
Query!
Trial website
https://clinicaltrials.gov/study/NCT02144038
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Novartis Pharmaceuticals
Query!
Address
0
0
Novartis Pharmaceuticals
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT02144038
Download to PDF