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

Novartis

Status and phase: Terminated; Phase 2

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

Treatments: Drug: Panobinostat

Study type: Interventional

Funder types: Industry

Identifiers

NCT00931762

CLBH589BUS58

Details and patient eligibility

About

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.

Enrollment: 35 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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35 participants in 1 patient group

Panobinostat

Experimental group

Description:

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.

Treatment:

Drug: Panobinostat