Panobinostat and Ruxolitinib In MyElofibrosis (PRIME Trial)

NCT01693601 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: GCO 12-1225
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, single arm, dose finding study to assess safety and tolerability of the oral combination of Panobinostat and Ruxolitinib in patients with myelofibrosis (MF) in chronic and accelerated phase.

Conditions

Myelofibrosis

Keywords

Myelofibrosis; Panobinostat; Ruxolitinib

Outcome Measures

Primary Outcomes (2)

• Number of Patients That Achieve Stable Disease or Clinical Improvement

  Number of patients that have either stable disease or clinical improvement treatment response as defined by the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT). Stable disease (SD) - response that is not complete remission, partial remission, clinical improvement, anemia response, spleen response, symptoms response, or progressive disease. Clinical improvement (CI) - a response in anemia, splenomegaly, or MF-SB that is not associated with progressive splenomegaly or increase in severity of anemia, thrombocytopenia, or neutropenia.

  at least 6 months

• Number of Participants Who Experienced Dose-Limiting (DLTs)

  Panobinostat related adverse events requiring dose reduction or discontinuing prior to Cycle 6, Day 29 (C6D29)

  up to cycle 6, day 29

Secondary Outcomes (4)

• Percent Change in Spleen Volume

  Baseline and Cycle 6, Day 29

• Percent Change in Spleen Size for Responders and Non-responders

  Cycle 6, Day 29

• Percent Change in Spleen Length

  Cycle 6, Day 29

• Number of Participants With Percent Change on Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF)

  baseline, C1D1 and Cycle 6 Day 29

Study Arms (1)

Panobinostat and Ruxolitinib

EXPERIMENTAL

Combination of Panobinostat and Ruxolitinib

Drug: Panobinostat; Drug: Ruxolitinib

Interventions

Panobinostat DRUG

PO TIW QOW or PO TIW QW

Also known as: LBH589

Panobinostat and Ruxolitinib

Ruxolitinib DRUG

PO BID x 28 days

Also known as: INCB424, Jakafi

Panobinostat and Ruxolitinib

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
• Intermediate-2 and higher by IWG-MRT Post PV/ET MF and PMF patients either in
• Chronic Phase (MF-CP)
• Accelerated Phase (MF-AP)
• Patients must meet the following laboratory criteria:
• ANC ≥ .750 x 109/L
• Platelets ≥ 75 x 109/L
• Creatinine ≤ 1.5 x ULN,
• AST and ALT ≤ 2.5 x ULN
• Serum bilirubin ≤ 1.5 x ULN (unless Gilbert's syndrome and evidence of hemolysis)
• 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:

• Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first PANOBINOSTAT treatment.
• Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:
• With permanent cardiac pacemaker
• Resting bradycardia defined as \<50 beats per minute
• QTcF \>450 msec on screening ECG
• Complete Left bundle branch block, bifascicular block
• Any clinically significant ST segment and/or T-wave abnormalities
• Symptomatic congestive heart failure (NYHA class III-IV)
• Impairment of GI function or GI disease that may significantly alter the absorption of PANOBINOSTAT or RUXOLITINIB
• 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
• Patients using medications that have a relative risk of prolonging the QT interval or inducing torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug
• Concomitant use of CYP3A4 inhibitors
• Patients who have received targeted agents within 2 weeks or within 5 half-lives of the agent and active metabolites (whichever is longer) and who have not recovered from side effects of those therapies.
• Chemotherapy within 3 weeks prior to screening are excluded (other than hydroxyurea at stable doses and will be discontinued 24 hours prior to starting study drug).
• Patients with an active bleeding tendency or are receiving any treatment with therapeutic doses of sodium warfarin (Coumadin®) or coumadin derivatives. Patients will be allowed to enter study on aspirin at doses of 81mg/d.

Sponsors & Collaborators

• John Mascarenhas: lead

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Related Publications (1)

• Mascarenhas J, Marcellino BK, Lu M, Kremyanskaya M, Fabris F, Sandy L, Mehrotra M, Houldsworth J, Najfeld V, El Jamal S, Petersen B, Moshier E, Hoffman R. A phase I study of panobinostat and ruxolitinib in patients with primary myelofibrosis (PMF) and post--polycythemia vera/essential thrombocythemia myelofibrosis (post--PV/ET MF). Leuk Res. 2020 Jan;88:106272. doi: 10.1016/j.leukres.2019.106272. Epub 2019 Nov 16.

  PMID: 31778911 RESULT

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

Panobinostat; ruxolitinib

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: John Mascarenhas
• Organization: Icahn School of Medicine at Mount Sinai

john.mascarenhas@mssm.edu

212-241-3417

Study Officials

• John Mascarenhas, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine, Hematology and Medical Oncology

Study Record Dates

• First Submitted: September 14, 2012
• First Posted: September 26, 2012
• Study Start: January 1, 2013
• Primary Completion: May 18, 2018
• Study Completion: May 18, 2018
• Last Updated: October 31, 2023
• Results First Posted: October 31, 2023

Record last verified: 2023-10

Locations

US (1)