Study of the Safety of PIM447 in Combination With Ruxolitinib (INC424) and LEE011 in Patients With Myelofibrosis

NCT ID: NCT02370706

Last Updated: 2022-02-09

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

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-05-21

Study Completion Date

2020-11-09

Brief Summary

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This is a phase Ib study with the primary purpose is to estimate the MTD and/or RDE for the triple combination of PIM447, formerly LGH447, plus ruxolitinib and LEE011 as well as for the doublets, PIM447 plus ruxolitinib, and LEE011 plus ruxolitinib, in patients with myelofibrosis (MF). Each regimen will be assessed for safety, tolerability, pharmacokinetics (PK) and pharmacodynamic effects, and preliminary anti-myelofibrosis activity, including changes in spleen volume, JAK2V617F allele burden, and hematologic response.

Detailed Description

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Conditions

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Myelofibrosis

Study Design

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Allocation Method

NA

Intervention Model

PARALLEL

Primary Study Purpose

HEALTH_SERVICES_RESEARCH

Blinding Strategy

NONE

Study Groups

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Dose Escalation Arm 1

Group Type EXPERIMENTAL

PIM447

Intervention Type DRUG

pan-pim inhibitor

Ruxolitinib

Intervention Type DRUG

JAK1/JAK2 inhibitor

Dose Escalation Arm 2

Group Type EXPERIMENTAL

Ruxolitinib

Intervention Type DRUG

JAK1/JAK2 inhibitor

LEE011

Intervention Type DRUG

CDK4/6 inhibitor

Dose Escalation Arm 3

Group Type EXPERIMENTAL

PIM447

Intervention Type DRUG

pan-pim inhibitor

Ruxolitinib

Intervention Type DRUG

JAK1/JAK2 inhibitor

LEE011

Intervention Type DRUG

CDK4/6 inhibitor

Dose Expansion Arm 1

Group Type EXPERIMENTAL

PIM447

Intervention Type DRUG

pan-pim inhibitor

Ruxolitinib

Intervention Type DRUG

JAK1/JAK2 inhibitor

Dose Expansion Arm 2

Group Type EXPERIMENTAL

Ruxolitinib

Intervention Type DRUG

JAK1/JAK2 inhibitor

LEE011

Intervention Type DRUG

CDK4/6 inhibitor

Dose Expansion Arm 3

Group Type EXPERIMENTAL

PIM447

Intervention Type DRUG

pan-pim inhibitor

Ruxolitinib

Intervention Type DRUG

JAK1/JAK2 inhibitor

LEE011

Intervention Type DRUG

CDK4/6 inhibitor

Interventions

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PIM447

pan-pim inhibitor

Intervention Type DRUG

Ruxolitinib

JAK1/JAK2 inhibitor

Intervention Type DRUG

LEE011

CDK4/6 inhibitor

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
* Patient must be diagnosed with JAK2V617F-positive primary or secondary MF.
* Dose-escalation and Expansion parts: Patients with a \< 35% reduction in spleen volume by MRI/CT or \< 50% reduction in spleen size by physical exam, with or without corresponding symptomatic improvement, after at least 6 months of treatment with single agent ruxolitinib at an optimal dose level in line with the label recommendations. Expansion parts only: Ruxolitinib-naive patients and patients who have been previously treated with single agent ruxolitinib and are relapsed and/or refractory.
* Patients must have splenomegaly measuring at least 5 cm by MRI at baseline.
* Have adequate bone marrow function:

* Platelets ≥ 100,000 mm3 without the assistance of growth factors or platelet transfusions
* Absolute Neutrophil Count (ANC) ≥ 1500/mm3 without growth factor support within 7 days prior to testing
* Hemoglobin ≥ 9 g/dL.

Exclusion Criteria

* Systemic antineoplastic therapy (including unconjugated therapeutic antibodies, toxin immunoconjugates, and alpha-interferon) or any experimental therapy within 14 days or 5 half-lives, whichever is shorter, before the first dose of study treatment
* Major surgery within 2 weeks before the first dose of either study drug.
* Patients who have had splenic irradiation within 2 weeks prior to Screening or prior splenectomy.
* Patients with AML, MDS, or peripheral blasts ≥ 10 %
* Prior autologous or allogeneic stem cell transplant at any time.
* Patients who are currently receiving treatment with a prohibited medication that cannot be discontinued at least one week prior to the start of treatment:

* substrates of CYP3A4/5, CYP2B6 or CYP2D6 that have a narrow therapeutic window
* strong inhibitors of CYP3A4/5 or CYP2D6
* potent inducers of CYP3A4/5 or CYP2D6
* Serum total bilirubin \> 1.5 x upper limit of normal (ULN) except in patients with Gilbert's syndrome who are excluded if the total bilirubin is \> 3.0 x ULN or direct bilirubin \> 1.5 x ULN, or aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) or ALT (SGPT) \> 3 x ULN, except in patients with MF involvement of the liver who are excluded if AST or ALT \> 5 x ULN.
* Serum creatinine \> 1.5 x ULN or calculated creatinine clearance \< 60 ml/min according to Cockcroft-Gault equation
* Electrolyte abnormalities CTCAE grade ≥ 2 (e.g. serum potassium, magnesium and calcium) unless they can be repleted during screening and are deemed not clinically significant by the Investigator.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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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

VIC, Melbourne, Australia

Site Status

Novartis Investigative Site

Toronto, Ontario, Canada

Site Status

Novartis Investigative Site

Villejuif, , France

Site Status

Novartis Investigative Site

Mainz, , Germany

Site Status

Novartis Investigative Site

Ulm, , Germany

Site Status

Novartis Investigative Site

Florence, FI, Italy

Site Status

Novartis Investigative Site

Rotterdam, , Netherlands

Site Status

Novartis Investigative Site

Singapore, , Singapore

Site Status

Novartis Investigative Site

London, , United Kingdom

Site Status

Countries

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Australia Canada France Germany Italy Netherlands Singapore United Kingdom

Related Links

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https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17874

Results for CPIM447X2104C can be found on the Novartis Clinical Trial Results Website.

Other Identifiers

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2014-003801-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CPIM447X2104C

Identifier Type: -

Identifier Source: org_study_id

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