NCT01433445

Brief Summary

This study will assess safety as well as establish a Recommended Phase II dose of the combination of panobinostat and ruxolitinib in patients with or without the JAK2V617F mutation who have been diagnosed with primary myelofibrosis (PMF), Post Essential Thrombocythemia Myelofibrosis (PET MF), or Post-Polycythemia Vera Myelofibrosis (PPV MF).

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
61

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Nov 2011

Longer than P75 for phase_1

Geographic Reach
5 countries

10 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 27, 2011

Completed
3 months until next milestone

First Posted

Study publicly available on registry

September 14, 2011

Completed
2 months until next milestone

Study Start

First participant enrolled

November 1, 2011

Completed
8.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 22, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 22, 2020

Completed
Last Updated

June 25, 2021

Status Verified

June 1, 2021

Enrollment Period

8.6 years

First QC Date

June 27, 2011

Last Update Submit

June 22, 2021

Conditions

Idiopathic MyelofibrosisPost Essential Thrombocythemia MyelofibrosisPost Polycythemia-Vera Myelofibrosis

Keywords

MyelofibrosisPanobinostatLBH589RuxolitinibMFPMFPPVPPV-MFPETPET-MFJAK2DACi

Outcome Measures

Primary Outcomes (1)

  • Rate of dose limiting toxicities at the different dose levels

    Cycle 1 (a cycle = 28 days)

Secondary Outcomes (4)

  • Rate of adverse events, serious adverse events, notable laboratory, vital signs and ECG results by dose level

    From screening until safety follow up visit (30 days after last treatment), approx. 8.5 years

  • AUC of ruxolitinib and panobinostat at various dose levels

    Ruxolitinib on days 1,2 and 6; Panobinostat on days 2-3 and days 6-7

  • Cmax of ruxolitinib and panobinostat at various dose levels

    Ruxolitinib on days 1,2 and 6; Panobinostat on days 2-3 and days 6-7

  • Tmax of ruxolitinib and panobinostat at various dose levels

    Ruxolitinib on days 1,2 and 6; Panobinostat on days 2-3 and days 6-7

Study Arms (6)

Cohort 1

EXPERIMENTAL

Subjects will be treated with ruxolitinib 5 mg twice daily (BID) and panobinostat 10 mg three times per week (TIW) every other week (QOW) on a 28 day cycle

Drug: panobinostatDrug: ruxolitinib

Cohort 2

EXPERIMENTAL

Subjects will be treated with ruxolitinib 10 mg twice daily (BID) and panobinostat 10 mg three times per week (TIW) every other week (QOW) on a 28 day cycle

Drug: panobinostatDrug: ruxolitinib

Cohort 3

EXPERIMENTAL

Subjects will be treated with ruxolitinib 15 mg twice daily (BID) and panobinostat 10 mg three times per week (TIW) every other week (QOW) on a 28 day cycle

Drug: panobinostatDrug: ruxolitinib

Cohort 4

EXPERIMENTAL

Subjects will be treated with ruxolitinib 15 mg twice daily (BID) and panobinostat 15 mg three times per week (TIW) every other week (QOW) on a 28 day cycle

Drug: panobinostatDrug: ruxolitinib

Cohort 5

EXPERIMENTAL

Subjects will be treated with ruxolitinib 15 mg twice daily (BID) and panobinostat 20 mg three times per week (TIW) every other week (QOW) on a 28 day cycle

Drug: panobinostatDrug: ruxolitinib

Cohort 6/6+

EXPERIMENTAL

Subjects will be treated with ruxolitinib 15 mg twice daily (BID) and panobinostat 25 mg three times per week (TIW) every other week (QOW) on a 28 day cycle

Drug: panobinostatDrug: ruxolitinib

Interventions

panobinostatDRUG

Given 3 times a week, every other week in 28-day cycles.

Also known as: LBH589
Cohort 1Cohort 2Cohort 3Cohort 4Cohort 5Cohort 6/6+
ruxolitinibDRUG

Given twice daily in 28-day cycles.

Also known as: INC424
Cohort 1Cohort 2Cohort 3Cohort 4Cohort 5Cohort 6/6+

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Diagnosis of myelofibrosis, either PMF, PPV or PET MF
  • Palpable splenomegaly ≥ 5cm
  • May have been previously treated with either panobinostat or ruxolitinib (unless discontinued for clinically relevant toxicities)
  • Acceptable lab ranges for all organ systems
  • Specifically: Platelet count \> 100,000 not reached with the aide of transfusions
  • Blast count \< 10% at screening
  • ECOG ≤ 2
  • Must be able to discontinue all drugs being used to treat MF at least 7 days prior to starting study drug

You may not qualify if:

  • Active malignancy
  • Clinically significant heart disease
  • Splenic irradiation within 12 months of starting study drug
  • Need for ongoing systemic anticoagulation with the exception of Aspirin \< 150mg/day or Low Molecular Weight Heparin
  • History of platelet dysfunction or bleeding disorder in the 6 months prior to screening
  • Patient is at risk for spontaneous bleeding
  • Willing and/or eligible for stem-cell transplantation
  • Impairment of gastro-intestinal function that may impact the absorption of study treatment
  • Unwilling to use highly effective methods of contraception during dosing and for 13 weeks (female participants) or for 6 months (male participants and their female partners) after stopping study treatment

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

Novartis Investigative Site

Paris, 75010, France

Location

Novartis Investigative Site

Villejuif, 94800, France

Location

Novartis Investigative Site

Magdeburg, 39120, Germany

Location

Novartis Investigative Site

Mainz, 55131, Germany

Location

Novartis Investigative Site

Dublin, DUBLIN 8, Ireland

Location

Novartis Investigative Site

Galway, Ireland

Location

Novartis Investigative Site

Florence, FI, 50134, Italy

Location

Novartis Investigative Site

Reggio Calabria, RC, 89124, Italy

Location

Novartis Investigative Site

Varese, VA, 21100, Italy

Location

Novartis Investigative Site

London, SE1 9RT, United Kingdom

Location

Related Links

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

Panobinostatruxolitinib

Condition Hierarchy (Ancestors)

Myeloproliferative DisordersBone Marrow DiseasesHematologic DiseasesHemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Hydroxamic AcidsHydroxylaminesAminesOrganic ChemicalsHydroxy AcidsCarboxylic AcidsIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Novartis Pharmaceuticals

    Novartis Pharmaceuticals

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 27, 2011

First Posted

September 14, 2011

Study Start

November 1, 2011

Primary Completion

June 22, 2020

Study Completion

June 22, 2020

Last Updated

June 25, 2021

Record last verified: 2021-06

Data Sharing

IPD Sharing
Will not share

Locations

IT(3)GB(1)FR(2)DE(2)IE(2)