LBH589 (Panobinostat) for the Treatment of Myelofibrosis

NCT01298934 | Unknown Phase 1 DMC

• 2 other identifiers: GCO 08-0572LBH589-JM
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

LBH589 is an oral drug that targets the myelofibrosis cells in the bone marrow and induces cell death by allowing for the expression of certain suppressed genes that are important in regulating cell survival. Based on laboratory studies, the hypothesis is that this drug will selectively kill the stem cells responsible for causing myelofibrosis and result in reduction in spleen size and ultimately restoration of normal bone marrow function.

Conditions

Primary Myelofibrosis; Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase; Post-Essential Thrombocythemia Related Myelofibrosis

Outcome Measures

Primary Outcomes (2)

• To assess the safety and tolerability of oral LBH589 in patients with PMF, post-PV/ET MF

  Phase I

  28 days

• Evaluation of treatment response by International Working Group for Myelofibrosis Research and Treatment (IWG-MRT)

  Phase II

  6 months

Secondary Outcomes (1)

• Assess changes in biomarkers

  6 months

Study Arms (1)

LBH589

EXPERIMENTAL

Dose escalation study starting at 20mg by mouth three times a week, given weekly for 24 weeks in the phase I portion of the study.

Drug: LBH589

Interventions

LBH589 DRUG

Dose escalation study starting at 20mg by mouth three times a week, given weekly for 24 weeks in the phase I portion of the study.

Also known as: Panobinostat

LBH589

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged ≥ 18 years old
• Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
• Newly diagnosed MF with intermediate or high risk Lille Scoring System (Hb\<10g/dL, WBC \<4.0 or \>30 X 109/L; risk group 1=intermediate and 2= high), or symptomatic splenomegaly that is \>10cm below costal margin.
• Previously treated MF that are refractory, intolerant or relapsed in disease
• Patients must meet the following laboratory criteria:
• ANC ≥ 1.0 x 109/L
• Platelets ≥ 60 x 109/L
• Calculated CrCl ≥ 45 mL/min (MDRD Formula)
• AST and ALT ≤ 2.5 x ULN
• Serum bilirubin \< 1.5 x ULN
• Albumin \> 3.0 g/dl
• Serum potassium ≥ LLN
• Total serum calcium \[corrected for serum albumin\] or ionized calcium ≥LLN,
• Serum magnesium ≥ LLN
• Serum phosphorus ≥ LLN

You may not qualify if:

• Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer
• Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first LBH589 treatment
• Peripheral neuropathy \> 1
• Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:
• Patients with congenital long QT syndrome
• History or presence of sustained ventricular tachyarrhythmia.(Patients with a history of atrial arrhythmia are eligible but should be discussed with the Sponsor prior to enrollment)
• Any history of ventricular fibrillation or torsade de pointes
• Bradycardia defined as HR\< 50 bpm. Patients with pacemakers are eligible if HR ≥ 50 bpm.
• Screening ECG with a QTc \> 450 msec
• Right bundle branch block + left anterior hemiblock (bifascicular block)
• Patients with myocardial infarction or unstable angina ≤ 6 months prior to starting study drug
• Other clinically significant heart disease (e.g., CHF NY Heart Association class III or IV , uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
• Impairment of GI function or GI disease that may significantly alter the absorption of LBH589
• Patients with diarrhea \> CTCAE grade 1
• Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes or active or uncontrolled infection) including abnormal laboratory values, that could cause unacceptable safety risks or compromise compliance with the protocol

Sponsors & Collaborators

• Ronald Hoffman: lead
• Novartis: collaborator

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Primary Myelofibrosis; Polycythemia Vera

Interventions

Panobinostat

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Ronald Hoffman, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 16, 2011
• First Posted: February 18, 2011
• Study Start: September 1, 2009
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: March 6, 2015

Record last verified: 2015-03

Locations

US (1)