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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01730248




Registration number
NCT01730248
Ethics application status
Date submitted
12/11/2012
Date registered
21/11/2012

Titles & IDs
Public title
A Study to Find the Maximum Tolerated Dose of the Experimental Combination of the Drugs INC424 and BKM120 in Patients With Primary or Secondary Myelofibrosis
Scientific title
A Phase Ib, Open-label, Multi-center, Two-arm, Dose-finding Study to Assess Safety and Efficacy of the Oral Combination or INC424 (INC424) and BKM120 in Patients With Primary Myelofibrosis (PMF), Postpolycythemia Vera-myelofibrosis (PPV-MF), or Post-essential Thrombocythemia-myelofibrosis (PET-MF)
Secondary ID [1] 0 0
CINC424A2104
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myelofibrosis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - INC424
Treatment: Drugs - BKM120

Experimental: JAK Inhibitor Naive - Two treatment periods applicable to all patients; Treatment Period (6 cycles / 28 days per cycle) and Extension Period ( 6 or more cycles of 28 days, with visits every 28days for 6 cycles and then visits every 12 weeks) following the treatment period dependent on patient continued eligibility. Two Study Phases: Dose Escalation Phase to determine maximum tolerated dose (MTD) / Recommended Phase II dose (RPIID) \& an Expansion Phase

Experimental: Prior JAK Inhibitor - Two treatment periods applicable to all patients; Treatment Period (6 cycles / 28 days per cycle) and Extension Period (6 or more cycles of 28 days, with visits every 28 days for 6 cycles then visits every 12 weeks) following the treatment period dependent on patient continued eligibility. Two Study Phases: Dose Escalation Phase to determine MTD / RPIID \& an Expansion Phase


Treatment: Drugs: INC424
5 mg tablets administered orally twice daily

Treatment: Drugs: BKM120
10 mg and 50 mg hard gelatin capsules administered orally once daily
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of dose limiting toxicities
Timepoint [1] 0 0
baseline, when the maximum tolerated dose is established.
Secondary outcome [1] 0 0
Frequency of adverse events
Timepoint [1] 0 0
after each cohort is enrolled at baseline until the maximum tolerated dose is established
Secondary outcome [2] 0 0
Frequency of serious adverse events
Timepoint [2] 0 0
after each cohort is enrolled at baseline until the maximum tolerated dose is established
Secondary outcome [3] 0 0
Abnormalities in vital signs
Timepoint [3] 0 0
baseline, days 2, 8, 15, 22 of cycle 1, day 1 and 15 at Cycle 2, Day 1 from cycle 3 to 12, day 28 on Cycle 12 and every 12 weeks from Week 60 to 96 and at End of treatment
Secondary outcome [4] 0 0
Laboratory test values including Imaging (electrocardiograms (ECGs), abdominal MRI/CT, ECHO/MUGA
Timepoint [4] 0 0
Day 1, 2, 5, 8, 11, 18, 22, 25 of cycle 1, weekly in cycle 2, then at every scheduled visit including End of treatment visit
Secondary outcome [5] 0 0
Maximum plasma concentration (Cmax)
Timepoint [5] 0 0
pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours on days 1, 2, and 8
Secondary outcome [6] 0 0
Maximum plasma concentration time (Tmax)
Timepoint [6] 0 0
pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours on days 1, 2, and 8
Secondary outcome [7] 0 0
Area under the plasma concentration time curve (AUC)
Timepoint [7] 0 0
pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours on days 1, 2, and 8
Secondary outcome [8] 0 0
Maximum plasma concentration (Cmax)
Timepoint [8] 0 0
pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 24 hours on days 2 and 8
Secondary outcome [9] 0 0
Maximum plasma concentration time (Tmax)
Timepoint [9] 0 0
pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 24 hours on days 2 and 8
Secondary outcome [10] 0 0
Area under the plasma concentration time curve (AUC)
Timepoint [10] 0 0
pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 24 hours on days 2 and 8
Secondary outcome [11] 0 0
Duration of adverse events
Timepoint [11] 0 0
after each cohort is enrolled at baseline until the maximum tolerated dose is established
Secondary outcome [12] 0 0
Severity of adverse events
Timepoint [12] 0 0
after each cohort is enrolled at baseline until the maximum tolerated dose is established
Secondary outcome [13] 0 0
Severity of serious adverse events
Timepoint [13] 0 0
after each cohort is enrolled at baseline until the maximum tolerated dose is established
Secondary outcome [14] 0 0
Duration of serious adverse events
Timepoint [14] 0 0
after each cohort is enrolled at baseline until the maximum tolerated dose is established

Eligibility
Key inclusion criteria
* Diagnosed with PMF, PPV-MF or PET-MF irrespective of JAK2 mutation status
* Myelofibrosis patients requiring therapy must be classified as intermediate risk level 1 )1 or more prognostic factors defined by IWG) with at least one criteria other than age
* Must have palpable spleen of at least 5 cm from the costal margin to the point of greatest splenic profusion at Screening
* Must have active symptoms of MF (one symptom score of at least 5 or two symptom scores of at least 3 at Screening) (per MFSSF 0-10)
* PLT counts > or = 75X 10^9/L at Screening or Cycle 1 Day 1 (not with aid of transfusions
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Pregnant or nursing women
* WOCBP not using highly effective methods of contraception
* Sexually active males who refuse condom use
* Previous Treatment with one of the following: PI3 K inhibitors and AKT inhibitors; JAK inhibitors that resulted in clinically significant toxicities per the Investigator;
* Patients who have had splenic irradiation within 12 months prior to Screening
* Patients with specific mood disorders
* Any history of bleeding diathesis
* Patients receiving the following treatments / medications:

EIAED within 2 wks. prior to study treatment; medication known to prolong QT interval or induce Torsades de Pointes; treatment with potent systemic systemic inhibitor or systemic inducer of CYP3A4; any use of drug that interferes with coagulation or inhibits PLT function

-current and willing candidates for a stem cell transplantation

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
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/12/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
28/09/2017
Sample size
Target
Accrual to date
Final
63
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Herston
Recruitment hospital [2] 0 0
Novartis Investigative Site - Melbourne
Recruitment postcode(s) [1] 0 0
4029 - Herston
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Vienna
Country [2] 0 0
France
State/province [2] 0 0
Paris
Country [3] 0 0
Germany
State/province [3] 0 0
Berlin
Country [4] 0 0
Germany
State/province [4] 0 0
Rostock
Country [5] 0 0
Israel
State/province [5] 0 0
Jerusalem
Country [6] 0 0
Israel
State/province [6] 0 0
Ramat Gan
Country [7] 0 0
Italy
State/province [7] 0 0
FI
Country [8] 0 0
Italy
State/province [8] 0 0
VA
Country [9] 0 0
Singapore
State/province [9] 0 0
Singapore
Country [10] 0 0
Spain
State/province [10] 0 0
Madrid
Country [11] 0 0
United Kingdom
State/province [11] 0 0
Birmingham
Country [12] 0 0
United Kingdom
State/province [12] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Incyte Corporation
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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/NCT01730248