A Study to Evaluate Safety and Efficacy of Panobinostat in Participants With Primary Myelofibrosis

NCT00931762 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: CLBH589BUS58
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 9

Brief Summary

This study assessed the safety and efficacy of Panobinostat as a single agent in the treatment of Primary Myelofibrosis, Post-Polycythemia Vera and Post-Essential Thrombocythemia. There were two cohorts - participants with JAK2 mutation and participants without JAK2 mutation.

Conditions

Primary Myelofibrosis; Post-Polycythemia Vera; Post-Essential Thrombocytopenia

Keywords

Bone marrow; Myelofibrosis; JAK2mutation; Post-Polycythemia Vera; Post-Essential Thrombocytopenia

Outcome Measures

Primary Outcomes (1)

• Overall Response (OR) Rate Per International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) Criteria

  Overall response (OR) = Complete remission (CR) + Partial remission (PR) + Clinical improvement (CI). CR: complete resolution of disease-related symptoms and signs with hemoglobin level 110 grams per deciliter (g/L), platelet count 100 x 10\^9/liter (L), and absolute neutrophil count (ANC) 1.0 x 10\^9/L, all 3 blood counts \< upper normal limit (UNL), normal leukocyte differential, and bone marrow histologic remission. PR= all of the criteria for CR except the requirement for bone marrow histologic remission. CI= minimum 20 g/L increase in hemoglobin for transfusion or becoming transfusion independent or reduction in splenomegaly ≥ 50% or 100% increase in platelet count and absolute platelet count of 50 x 10\^9/L and 100% increase in ANC of at least 0.5 x 10\^9/L.

  Up to approximately 2 years

Secondary Outcomes (3)

• Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores At Cycle 6

  Baseline, Cycle 6 (each cycle was of 28 days)

• Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores

  Baseline, Cycles 2, and 4 (each cycle was of 28-days)

• Number of Participants With Adverse Events (AEs), and Serious Adverse Events (SAEs)

  AE: From the start of treatment up to 28 days after last study dose (up to approximately 2 years); SAE: From time of informed consent up to 4 weeks after last study dose (approximately 2 years)

Other Outcomes (2)

• Monthly Capsule Counts to Assess Compliance to Panobinostat Treatment

  Up to approximately 2 years

• To Compare the Response to Panobinostat in Patients With the JAK2 V617F Mutation to Those Without the JAK2 V617F Mutation

  Up to approximately 2 years

Study Arms (1)

Panobinostat

EXPERIMENTAL

Participants received panobinostat 40 mg, capsules, orally, with or without food, three times a week on Monday, Wednesday, and Friday for up to 6 treatment cycles (each cycle of 28-days) with dose adjustments possible.

Drug: Panobinostat

Interventions

Panobinostat DRUG

Panobinostat oral capsules

Also known as: LBH589, H-DAC Inhibitor

Panobinostat

Eligibility Criteria

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

You may qualify if:

• Diagnosis of myelofibrosis, either primary myelofibrosis (PMF), post- polycythemia vera (PV) or post-essential thrombocythemia (ET) myelofibrosis (MF) with international prognostic scoring system (IPSS) score of 2 (intermediate risk) or 3 (high risk) plus at least one of the following:
• Symptomatic spenomegaly (≥10 centimeter \[cm\] below costal margin \[BCM\]) Hemoglobin \< 10 or red cell transfusion dependent. (The presence of a janus kinase (JAK2) V617F mutation is not required for study entry).
• Participants must meet the following laboratory criteria:
• Participants can be either JAK2 V617F mutated or wild type.
• Serum potassium, magnesium, phosphorous, sodium, total calcium (corrected for serum albumin) or ionized calcium within normal limits (WNL) for the institution Note: Potassium, magnesium, phosphorous, sodium, and/or calcium supplements maybe given to correct values that are \< lower limit of normal (LLN). Post correction values must not be deemed to be a clinically significant abnormality prior to participants being dosed.
• Creatinine \< 1.5 X upper limit of normal (ULN) or calculated creatinine clearance (CrCl) ≥ 50 milliliter per minute (mL/min) (modification of diet in renal diseases \[MDRD\] formula).
• Aspartate aminotransferase \[AST\] and alanine transaminase \[ALT\] ≤ 2.5 x ULN.
• Serum total bilirubin ≤ 1.5 x ULN.
• Eastern cooperative oncology group (ECOG) performance status of ≤ 2.
• Clinically euthyroid. Note: Participants are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism.

You may not qualify if:

• Prior histone deacetylases (HDAC), deacetylase (DAC), heat shock protein 90 (HSP90) inhibitors or valproic acid for the treatment of cancer.
• Previous treatment with JAK2 inhibitors.
• Any participant who has previously received radiation therapy to ≥ 30% of the bone marrow.
• Impaired cardiac function or clinically significant cardiac diseases.
• Participant with unresolved diarrhoea ≥ grade 2.
• Participants 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.
• Participants who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of surgery.
• Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) not using an effective method of birth control. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months). Women of childbearing potential must have a negative serum pregnancy test at screening and at baseline.
• Male participants whose sexual partners are WOCBP not using effective birth control.
• Participants with a prior malignancy with in the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix).
• Participants with known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (9)

Mayo Clinic - Scottsdale

Scottsdale, Arizona, 85259, United States

Location

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Stanford Comprehensive Cancer Center

Stanford, California, 94305, United States

Location

Medical College of Georgia

Augusta, Georgia, 30912, United States

Location

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

New York Presbyterian Hospital - Weill Cornell Medical College

New York, New York, 10021, United States

Location

Related Publications (1)

• DeAngelo DJ, Mesa RA, Fiskus W, Tefferi A, Paley C, Wadleigh M, Ritchie EK, Snyder DS, Begna K, Ganguly S, Ondovik MS, Rine J, Bhalla KN. Phase II trial of panobinostat, an oral pan-deacetylase inhibitor in patients with primary myelofibrosis, post-essential thrombocythaemia, and post-polycythaemia vera myelofibrosis. Br J Haematol. 2013 Aug;162(3):326-35. doi: 10.1111/bjh.12384. Epub 2013 May 23.

  PMID: 23701016 RESULT

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

Panobinostat

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: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2009
• First Posted: July 2, 2009
• Study Start: August 31, 2009
• Primary Completion: August 29, 2011
• Study Completion: August 29, 2011
• Last Updated: July 30, 2021
• Results First Posted: July 30, 2021

Record last verified: 2021-07

Locations

US (9)