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

NCT ID: NCT01730248

Last Updated: 2020-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

63 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-12-18

Study Completion Date

2017-09-28

Brief Summary

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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.

Detailed Description

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Conditions

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Myelofibrosis

Keywords

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Myelofibrosis, PMF, PPV-MF, PET-MF, Primary Myelofibrosis, Post-polycythemia vera myelofibrosis, Post-essential thrombocythemia myelofibrosis

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

INC424

Intervention Type DRUG

5 mg tablets administered orally twice daily

BKM120

Intervention Type DRUG

10 mg and 50 mg hard gelatin capsules administered orally once daily

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

Group Type EXPERIMENTAL

INC424

Intervention Type DRUG

5 mg tablets administered orally twice daily

BKM120

Intervention Type DRUG

10 mg and 50 mg hard gelatin capsules administered orally once daily

Interventions

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INC424

5 mg tablets administered orally twice daily

Intervention Type DRUG

BKM120

10 mg and 50 mg hard gelatin capsules administered orally once daily

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Incyte Corporation

INDUSTRY

Sponsor Role collaborator

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Novartis Investigative Site

Herston, Queensland, Australia

Site Status

Novartis Investigative Site

Melbourne, Victoria, Australia

Site Status

Novartis Investigative Site

Vienna, , Austria

Site Status

Novartis Investigative Site

Paris, , France

Site Status

Novartis Investigative Site

Berlin, , Germany

Site Status

Novartis Investigative Site

Rostock, , Germany

Site Status

Novartis Investigative Site

Jerusalem, , Israel

Site Status

Novartis Investigative Site

Ramat Gan, , Israel

Site Status

Novartis Investigative Site

Florence, FI, Italy

Site Status

Novartis Investigative Site

Varese, VA, Italy

Site Status

Novartis Investigative Site

Singapore, , Singapore

Site Status

Novartis Investigative Site

Madrid, , Spain

Site Status

Novartis Investigative Site

Edgbaston, Birmingham, United Kingdom

Site Status

Novartis Investigative Site

London, , United Kingdom

Site Status

Novartis Investigative Site

London, , United Kingdom

Site Status

Countries

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Australia Austria France Germany Israel Italy Singapore Spain United Kingdom

Related Links

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https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17230

Results for INC424A2104 can be found on the Novartis Clinical Trial Results Website

Other Identifiers

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CINC424A2104

Identifier Type: -

Identifier Source: org_study_id