Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Novartis
Sponsor:
Collaborator:
Incyte Corporation
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01730248
First received: November 12, 2012
Last updated: May 21, 2014
Last verified: May 2014

November 12, 2012
May 21, 2014
December 2012
January 2016   (final data collection date for primary outcome measure)
Incidence of dose limiting toxicities [ Time Frame: baseline, when the maximum tolerated dose is established. ] [ Designated as safety issue: Yes ]
The incidence of dose limiting toxicities will be analyzed to establish the maximum tolerated dose. To assess the maximum tolerated dose, labs and adverse events are monitored.
Same as current
Complete list of historical versions of study NCT01730248 on ClinicalTrials.gov Archive Site
  • Frequency of adverse events [ Time Frame: after each cohort is enrolled at baseline until the maximum tolerated dose is established ] [ Designated as safety issue: Yes ]
    Adverse Events are monitored at each study visit and 30 days post last dose of study drug
  • Frequency of serious adverse events [ Time Frame: after each cohort is enrolled at baseline until the maximum tolerated dose is established ] [ Designated as safety issue: Yes ]
    Serious Adverse events monitored at each study visit and 30 days post last dose of study drug
  • Abnormalities in vital signs [ Time Frame: baseline, days 2, 8, 15, 22 of cycle 1, day 1 of every additional cycle ] [ Designated as safety issue: Yes ]
    cycle = 28 days for the first 12 cycles, then every 12 weeks thereafter
  • Laboratory test values including Imaging (electrocardiograms (ECGs), abdominal MRI/CT, ECHO/MUGA [ Time Frame: Days 2, 5, 8, 11, 18, 22 of cycle 1, weekly in cycle 2, then on every cycle visit thereafter ( every 28 days until cycle 12, then every 12 weeks thereafter) ] [ Designated as safety issue: Yes ]
    ECGs are performed baseline, days 2, 8, 15, 22 of cycle 1 then day 1 of every additional cycle. Magnetic resonance imaging (MRI) or Cat Scan (CT) performed at baseline, cycle 4, day 1, cycle 7 day 1, cycle 12 day 28, then every 24 weeks thereafter, and end of treatment. Echocardiography (ECHO) or Multiple Gated Acquisition (MUGA) is performed at baseline and then every 4 cycles until cycle 12, then every 24 weeks therafter or as clinically indicated. Hematology is performed at baseline and days 2, 5, 8, 11, 15, 18, 22 of cycle 1, weekly in cycle 2, then on every cycle visit thereafter (every 28 days until cycle 12, then every 12 weeks thereafter).
  • Maximum plasma concentration (Cmax) [ Time Frame: pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours on days 1, 2, and 8 ] [ Designated as safety issue: No ]
    To characterize the pharmacokinetics (PK) of INC424 alone or in combination with BKM120
  • Maximum plasma concentration time (Tmax) [ Time Frame: pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours on days 1, 2, and 8 ] [ Designated as safety issue: No ]
    To characterize the pharmacokinetics (PK) of INC424 alone or in combination with BKM120
  • Area under the plasma concentration time curve (AUC) [ Time Frame: pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours on days 1, 2, and 8 ] [ Designated as safety issue: No ]
    To characterize the pharmacokinetics (PK) of INC424 alone or in combination with BKM120
  • Maximum plasma concentration (Cmax) [ Time Frame: pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 24 hours on days 2 and 8 ] [ Designated as safety issue: No ]
    To characterize the pharmacokinetics (PK) of BKM120 alone or in combination with INC424
  • Maximum plasma concentration time (Tmax) [ Time Frame: pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 24 hours on days 2 and 8 ] [ Designated as safety issue: No ]
    To characterize the pharmacokinetics (PK) of BKM120 alone or in combination with INC424
  • Area under the plasma concentration time curve (AUC) [ Time Frame: pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 24 hours on days 2 and 8 ] [ Designated as safety issue: No ]
    To characterize the pharmacokinetics (PK) of BKM120 alone or in combination with INC424
  • Duration of adverse events [ Time Frame: after each cohort is enrolled at baseline until the maximum tolerated dose is established ] [ Designated as safety issue: Yes ]
    Adverse Events are monitored at each study visit and 30 days post last dose of study drug
  • Severity of adverse events [ Time Frame: after each cohort is enrolled at baseline until the maximum tolerated dose is established ] [ Designated as safety issue: Yes ]
    Adverse Events are monitored at each study visit and 30 days post last dose of study drug
  • Duration of serious adverse events [ Time Frame: after each cohort is enrolled at baseline until the maximum tolerated dose is established ] [ Designated as safety issue: Yes ]
    Serious Adverse events monitored at each study visit and 30 days post last dose of study drug
  • Severity of serious adverse events [ Time Frame: after each cohort is enrolled at baseline until the maximum tolerated dose is established ] [ Designated as safety issue: Yes ]
    Serious Adverse events monitored at each study visit and 30 days post last dose of study drug
  • Frequency of adverse events [ Time Frame: after each cohort is enrolled at baseline until the maximum tolerated dose is established ] [ Designated as safety issue: Yes ]
    Adverse Events are monitored at each study visit and 30 days post last dose of study drug
  • Frequency of serious adverse events [ Time Frame: after each cohort is enrolled at baseline until the maximum tolerated dose is established ] [ Designated as safety issue: Yes ]
    Serious Adverse events monitored at each study visit and 30 days post last dose of study drug
  • Abnormalities in vital signs [ Time Frame: baseline, days 2, 8, 15, 22 of cycle 1, day 1 of every additional cycle ] [ Designated as safety issue: Yes ]
    cycle = 28 days
  • Laboratory test values including Imaging (electrocardiograms (ECGs), abdominal MRI/CT, ECHO/MUGA [ Time Frame: Days 2, 5, 8, 11, 18, 22 and then weekly for every other cycle after ] [ Designated as safety issue: Yes ]
    ECGs are performed baseline, days 2, 8, 15, 22 of cycle 1 then day 1 of every additional cycle. Magnetic resonance imaging (MRI) or Cat Scan (CT) and Echocardiography (ECHO) or Multiple Gated Acquisition (MUGA) is performed at baseline and then every 3 cycles until the end of treatment. . Hematology is performed at baseline and days 2, 5, 8, 11, 15, 18, 22 and then weekly in subsequent cycles.
  • Maximum plasma concentration (Cmax) [ Time Frame: pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours on days 1, 2, and 8 ] [ Designated as safety issue: No ]
    To characterize the pharmacokinetics (PK) of INC424 alone or in combination with BKM120
  • Maximum plasma concentration time (Tmax) [ Time Frame: pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours on days 1, 2, and 8 ] [ Designated as safety issue: No ]
    To characterize the pharmacokinetics (PK) of INC424 alone or in combination with BKM120
  • Area under the plasma concentration time curve (AUC) [ Time Frame: pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours on days 1, 2, and 8 ] [ Designated as safety issue: No ]
    To characterize the pharmacokinetics (PK) of INC424 alone or in combination with BKM120
  • Maximum plasma concentration (Cmax) [ Time Frame: pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 24 hours on days 2 and 8 ] [ Designated as safety issue: No ]
    To characterize the pharmacokinetics (PK) of BKM120 alone or in combination with INC424
  • Maximum plasma concentration time (Tmax) [ Time Frame: pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 24 hours on days 2 and 8 ] [ Designated as safety issue: No ]
    To characterize the pharmacokinetics (PK) of BKM120 alone or in combination with INC424
  • Area under the plasma concentration time curve (AUC) [ Time Frame: pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 24 hours on days 2 and 8 ] [ Designated as safety issue: No ]
    To characterize the pharmacokinetics (PK) of BKM120 alone or in combination with INC424
  • Duration of adverse events [ Time Frame: after each cohort is enrolled at baseline until the maximum tolerated dose is established ] [ Designated as safety issue: Yes ]
    Adverse Events are monitored at each study visit and 30 days post last dose of study drug
  • Severity of adverse events [ Time Frame: after each cohort is enrolled at baseline until the maximum tolerated dose is established ] [ Designated as safety issue: Yes ]
    Adverse Events are monitored at each study visit and 30 days post last dose of study drug
  • Duration of serious adverse events [ Time Frame: after each cohort is enrolled at baseline until the maximum tolerated dose is established ] [ Designated as safety issue: Yes ]
    Serious Adverse events monitored at each study visit and 30 days post last dose of study drug
  • Severity of serious adverse events [ Time Frame: after each cohort is enrolled at baseline until the maximum tolerated dose is established ] [ Designated as safety issue: Yes ]
    Serious Adverse events monitored at each study visit and 30 days post last dose of study drug
Not Provided
Not Provided
 
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
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)

The purpose of this phase Ib clinical trial is to evaluate the safety of the combination of INC424 and BKM120 in the myelofibrosis population and to establish the maximum tolerated dose and or the Recommended Phase II dose of the combination guided by the Bayesian dose escalation model. INC424 has shown efficacy in myelofibrosis (MF) and is approved in the US and EU for the treatment of MF. BKM120 is a PI3K inhibitor. Preclinical and early clinical experience support inhibition of the PI3K/mTOR pathway in MF as aberrant activation of the pathway has been observed in MF models and may contribute to the pathogenesis of the disease.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Myelofibrosis
  • Drug: INC424
    5 mg tablets administered orally twice daily
  • Drug: BKM120
    10 mg and 50 mg hard gelatin capsules administered orally once daily
  • Experimental: JAK Inhibitor Naive
    Two treatment periods applicable to all patients; Treatment Period (6 cycles / 28 days per cycle) and Extension Period (6 cycles of 28 days, then cycles 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
    Interventions:
    • Drug: INC424
    • Drug: BKM120
  • Experimental: Prior JAK Inhibitor
    Two treatment periods applicable to all patients; Treatment Period (6 cycles / 28 days per cycle) and Extension Period (6 cycles of 28 days, then cycles 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
    Interventions:
    • Drug: INC424
    • Drug: BKM120
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
62
January 2016
January 2016   (final data collection date for primary outcome measure)

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

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

Both
18 Years and older
No
Contact: Novartis Pharmaceuticals +41613241111
Contact: Novartis Pharmaceuticals
Australia,   Austria,   France,   Germany,   Israel,   Italy,   Singapore,   Spain,   United Kingdom
 
NCT01730248
CINC424A2104
No
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Incyte Corporation
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP