Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Safety and Efficacy of Panobinostat in Patients With Primary Myelofibrosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00931762
First received: July 1, 2009
Last updated: November 15, 2012
Last verified: November 2012
  Purpose

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


Condition Intervention Phase
Primary Myelofibrosis
Post-Polycythemia Vera
Post-Essential Thrombocytopenia
Drug: Panobinostat
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Oral Panobinostat (LBH589), a Novel Deacetylase Inhibitor (DACi) in Patients With Primary Myelofibrosis (PMF), Post Essential Thrombocythemia (ET) Myelofibrosis and Post- Polycythemia Vera (PV) Myelofibrosis

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • To evaluate the overall response (CR, PR, and clinical improvement) to oral panobinostat as a single agent at 40 mg daily every Monday, Wednesday and Friday in patients with myelofibrosis. [ Time Frame: Upon enrollment of 13 participants into each cohort of the study and at the end of the study. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To compare the response to panobinostat in patients with the JAK2 V617F mutation to those without the JAK2 V617F mutation [ Time Frame: Upon enrollment of 13 participants into the study and at the end of the study ] [ Designated as safety issue: No ]
  • To evaluate the symptomatic improvement of myelofibrosis patients treated with panobinostat using the Myelofibrosis Symptom Assessment Form (MF-SAF) at baseline and after 2 and 4 months of treatment [ Time Frame: Upon enrollment of 13 participants in each cohort and at the end of the study ] [ Designated as safety issue: No ]
  • To evaluate the symptomatic improvement of myelofibrosis patients treated with panobinostat using the Myelofibrosis Symptom Assessment Form (MF-SAF) at baseline and after 2 and 4 months of treatment [ Time Frame: throughout the study ] [ Designated as safety issue: Yes ]
  • To assess compliance to panobinostat treatment as assessed by monthly capsule counts [ Time Frame: at the end of the study ] [ Designated as safety issue: No ]

Enrollment: 35
Study Start Date: July 2009
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: JAK2 Mutated Drug: Panobinostat
Panobinostat will be administered orally once a day on Monday, Wednesday and Friday at a fixed dose of 40 mg. A cycle is defined as 28 days of treatment.
Other Names:
  • LBH589
  • Panobinostat
  • H-DAC Inhibitor
Experimental: Non JAK2 Mutated Drug: Panobinostat
Panobinostat will be administered orally once a day on Monday, Wednesday and Friday at a fixed dose of 40mg. A cycle is defined as 28 days of treatment.
Other Names:
  • LBH589
  • Panobinostat
  • H-DAC Inhibitor

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

1. Diagnosis of myelofibrosis, either PMF, post-PV or post-ET MF with IPSS score of 2 (intermediate risk) or 3 (high risk) plus at least one of the following: Symptomatic spenomegaly (≥10cm BCM) Hemoglobin < 10 or red cell transfusion dependent. (The presence of a JAK2 V617F mutation is not required for study entry) 2. Patients must meet the following laboratory criteria:

  • Patients 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 < LLN. Post correction values must not be deemed to be a clinically significant abnormality prior to patients being dosed.
  • Creatinine < 1.5 X ULN or Calculated CrCl ≥ 50 mL/min (MDRD Formula)
  • AST and ALT ≤ 2.5 x ULN
  • Serum total bilirubin ≤ 1.5 x ULN 3. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2 4. Clinically euthyroid. Note: Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism.

Exclusion Criteria:

  1. Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer
  2. Previous treatment with JAK2 inhibitors
  3. Any patient who has previously received radiation therapy to ≥ 30% of the bone marrow
  4. Impaired cardiac function or clinically significant cardiac diseases
  5. Patient with unresolved diarrhea ≥ grade 2
  6. 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
  7. Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of surgery
  8. 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.
  9. Male patients whose sexual partners are WOCBP not using effective birth control
  10. Patients with a prior malignancy with in the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix)
  11. Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required Other protocol-defined inclusion/exclusion criteria may apply -
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00931762

Locations
United States, Arizona
Mayo Clinic - Scottsdale
Scottsdale, Arizona, United States, 85259
United States, California
City of Hope National Medical Center
Duate, California, United States, 91010
Stanford Comprehensive Cancer Center
Stanford, California, United States, 94305
United States, Georgia
Medical College of Georgia
Augusta, Georgia, United States, 30912
United States, Illinois
Northwestern University Feinberg School of Medicine
Chicago, Illinois, United States, 60611
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
Mayo Clinic - Rochester
Rochester, Minnesota, United States, 55905
United States, New York
New York Prebyterian Hospital - Weill Cornell Medical College
New York, New York, United States, 10021
Sponsors and Collaborators
Novartis Pharmaceuticals
  More Information

Additional Information:
No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00931762     History of Changes
Other Study ID Numbers: CLBH589BUS58
Study First Received: July 1, 2009
Last Updated: November 15, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Bone marrow
Myelofibrosis
JAK2mutation
Post-Polycythemia Vera
Post-Essential Thrombocytopenia

Additional relevant MeSH terms:
Polycythemia
Polycythemia Vera
Primary Myelofibrosis
Purpura, Thrombocytopenic
Thrombocytopenia
Blood Coagulation Disorders
Blood Platelet Disorders
Bone Marrow Diseases
Hematologic Diseases
Hemorrhage
Immune System Diseases
Myeloproliferative Disorders
Pathologic Processes
Purpura
Signs and Symptoms
Skin Manifestations
Thrombotic Microangiopathies
Panobinostat
Antineoplastic Agents
Enzyme Inhibitors
Histone Deacetylase Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014