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

Primary Myelofibrosis Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00931762
• Other study ID #: CLBH589BUS58
• Status: Terminated
• Phase: Phase 2
• Start date: August 31, 2009
• Est. completion date: August 29, 2011

Study information

• Verified date: July 2021
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 35
• Est. completion date: August 29, 2011
• Est. primary completion date: August 29, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. 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).

2. 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.

3. Eastern cooperative oncology group (ECOG) performance status of = 2.

4. Clinically euthyroid. Note: Participants are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism.

Exclusion Criteria:

1. Prior histone deacetylases (HDAC), deacetylase (DAC), heat shock protein 90 (HSP90) inhibitors or valproic acid for the treatment of cancer.

2. Previous treatment with JAK2 inhibitors.

3. Any participant who has previously received radiation therapy to = 30% of the bone marrow.

4. Impaired cardiac function or clinically significant cardiac diseases.

5. Participant with unresolved diarrhoea = grade 2.

6. 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.

7. Participants 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 participants whose sexual partners are WOCBP not using effective birth control.

10. 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).

11. Participants 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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Panobinostat
Panobinostat oral capsules

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Medical College of Georgia	Augusta	Georgia
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Northwestern University Feinberg School of Medicine	Chicago	Illinois
United States	City of Hope National Medical Center	Duarte	California
United States	New York Presbyterian Hospital - Weill Cornell Medical College	New York	New York
United States	Mayo Clinic - Rochester	Rochester	Minnesota
United States	Mayo Clinic - Scottsdale	Scottsdale	Arizona
United States	Stanford Comprehensive Cancer Center	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & 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-essent — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Monthly Capsule Counts to Assess Compliance to Panobinostat Treatment		Up to approximately 2 years
Other	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
Primary	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	Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores At Cycle 6	The MF-SAF consists of seven questions about key symptoms and impact of MF. Questions were scored on a scale of 0-10, with higher scores indicating more severe symptoms and greater inactivity. Questions 1-6 investigate the following symptoms: night sweats, pruritus/itching, abdominal discomfort, pain under the ribs, early satiety and bone/muscle pain. Question 7 asked participants to report levels of inactivity. Negative change from baseline indicates improvement.	Baseline, Cycle 6 (each cycle was of 28 days)
Secondary	Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores	The MF-SAF consists of seven questions about key symptoms and impact of MF. Questions were scored on a scale of 0-10, with higher scores indicating more severe symptoms and greater inactivity. Questions 1-6 investigate the following symptoms: night sweats, pruritus/itching, abdominal discomfort, pain under the ribs, early satiety and bone/muscle pain. Question 7 asked participants to report levels of inactivity. Negative change from baseline indicates improvement.	Baseline, Cycles 2, and 4 (each cycle was of 28-days)
Secondary	Number of Participants With Adverse Events (AEs), and Serious Adverse Events (SAEs)	An adverse event is the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after starting the study drug even if the event is not considered to be related to study drug. SAEs was an undesirable sign, symptom or medical condition which is: life-threatening, persistent or significant disability/incapacity, congenital anomaly/birth defect, requires hospitalizations or prolongation of hospitalizations, or is medically significant	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)