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Decision by Sponsor to to terminate the study early.
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| Name | Class |
|---|---|
| Incyte Corporation | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| JAK Inhibitor Naive | Experimental | 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 |
|
| Prior JAK Inhibitor | Experimental | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| INC424 | Drug | 5 mg tablets administered orally twice daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of dose limiting toxicities | 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. | baseline, when the maximum tolerated dose is established. |
| Measure | Description | Time Frame |
|---|---|---|
| Frequency of adverse events | Adverse Events are monitored at each study visit and 30 days post last dose of study drug | after each cohort is enrolled at baseline until the maximum tolerated dose is established |
| Frequency of serious adverse events |
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Inclusion Criteria:
Exclusion Criteria:
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
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Herston | Queensland | 4029 | Australia | ||
| Novartis Investigative Site |
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| Label | URL |
|---|---|
| Results for INC424A2104 can be found on the Novartis Clinical Trial Results Website | View source |
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| BKM120 | Drug | 10 mg and 50 mg hard gelatin capsules administered orally once daily |
|
Serious Adverse events monitored at each study visit and 30 days post last dose of study drug
| after each cohort is enrolled at baseline until the maximum tolerated dose is established |
| Abnormalities in vital signs | cycle = 28 days | 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 |
| Laboratory test values including Imaging (electrocardiograms (ECGs), abdominal MRI/CT, ECHO/MUGA | ECGs are performed baseline, days 2, 8, 15, 22 of cycle 1 then day 1 from Cycle 2 to cycle 12, and at cycle 12 day 28 and every 12 weeks and end of treatment. 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 , and end of treatment if not done in past 12 weeks. 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 until Week 96. Hematology is performed at baseline and days 2, 5, 8, 11, 15, 18, 22, 25 of cycle 1, weekly in cycle 2, then on every scheduled visit (D1 of Cycle 3 to 12, at Cycle 12 Day 28 ,then every 12 weeks) and end of treatment. | 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 |
| Maximum plasma concentration (Cmax) | To characterize the pharmacokinetics (PK) of INC424 alone or in combination with BKM120 | pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours on days 1, 2, and 8 |
| Maximum plasma concentration time (Tmax) | To characterize the pharmacokinetics (PK) of INC424 alone or in combination with BKM120 | pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours on days 1, 2, and 8 |
| Area under the plasma concentration time curve (AUC) | To characterize the pharmacokinetics (PK) of INC424 alone or in combination with BKM120 | pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours on days 1, 2, and 8 |
| Maximum plasma concentration (Cmax) | To characterize the pharmacokinetics (PK) of BKM120 alone or in combination with INC424 | pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 24 hours on days 2 and 8 |
| Maximum plasma concentration time (Tmax) | To characterize the pharmacokinetics (PK) of BKM120 alone or in combination with INC424 | pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 24 hours on days 2 and 8 |
| Area under the plasma concentration time curve (AUC) | To characterize the pharmacokinetics (PK) of BKM120 alone or in combination with INC424 | pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 24 hours on days 2 and 8 |
| Duration of adverse events | Adverse Events are monitored at each study visit and 30 days post last dose of study drug | after each cohort is enrolled at baseline until the maximum tolerated dose is established |
| Severity of adverse events | Adverse Events are monitored at each study visit and 30 days post last dose of study drug | after each cohort is enrolled at baseline until the maximum tolerated dose is established |
| Severity of serious adverse events | Serious Adverse events monitored at each study visit and 30 days post last dose of study drug | after each cohort is enrolled at baseline until the maximum tolerated dose is established |
| Duration of serious adverse events | Adverse Events are monitored at each study visit and 30 days post last dose of study drug | after each cohort is enrolled at baseline until the maximum tolerated dose is established |
| Melbourne |
| Victoria |
| 3000 |
| Australia |
| Novartis Investigative Site | Vienna | A-1090 | Austria |
| Novartis Investigative Site | Paris | 75010 | France |
| Novartis Investigative Site | Berlin | 13353 | Germany |
| Novartis Investigative Site | Rostock | 18057 | Germany |
| Novartis Investigative Site | Jerusalem | 91120 | Israel |
| Novartis Investigative Site | Ramat Gan | 5265601 | Israel |
| Novartis Investigative Site | Florence | FI | 50134 | Italy |
| Novartis Investigative Site | Varese | VA | 21100 | Italy |
| Novartis Investigative Site | Singapore | 169608 | Singapore |
| Novartis Investigative Site | Madrid | 28041 | Spain |
| Novartis Investigative Site | Edgbaston | Birmingham | B15 2WB | United Kingdom |
| Novartis Investigative Site | London | NW1 2BU | United Kingdom |
| Novartis Investigative Site | London | SE1 9RT | United Kingdom |
| ID | Term |
|---|---|
| D055728 | Primary Myelofibrosis |
| ID | Term |
|---|---|
| D009196 | Myeloproliferative Disorders |
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| C540383 | ruxolitinib |
| C571178 | NVP-BKM120 |
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