Panobinostat in Combination With Idarubicin and Cytarabine in Patients Aged 65 Years or Older With Newly Diagnosed Acute Myeloblastic Leukaemia (AML)

• Status: Completed
• Trial end date: 2018-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This protocol is a multicenter, national, open-label, single-arm, non-controlled study designed to establish the efficacy (in terms of response and survival) and safety of panobinostat in combination with idarubicin and cytarabine and in monotherapy in patients with newly-diagnosed AML aged 65 years or older.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: PETHEMA Foundation
• Treatments: Cytarabine; Idarubicin; Panobinostat

Criteria

Inclusion Criteria:

• The patient should, in the investigator's opinion, be able to meet all clinical trial requirements.

• The patient should have voluntarily give the informed consent before performing any study test that is not part of the regular care of the patients.

• Age > 65 years.

• The patient should be diagnosed with AML according to the standard criteria of the World Health Organisation (WHO) (see Appendix 8).

• The patient should not have received any prior treatment for AML.

• The patient should have a performance status measured by the ECOG scale <= 2 .

• The patient should have the following laboratory values prior to the start of the treatment:

• Aspartate transaminase (AST): ≤ 2.5 x the upper normal ranges.

• Alanine transaminase (ALT): ≤ 2.5 x the upper normal ranges.

• Total bilirubin: ≤ 1.5 x the upper normal ranges.

• Alkaline phosphatase: ≤ 2.5 x the upper normal ranges.

• Serum creatinine ≤ 2 mg/dl.

• Serum potassium, magnesium, phosphorus, sodium, total calcium (corrected for serum albumin) or ionized calcium within normal limits (WNL) for the institution. Note: Electrolytes (supplemental therapy) should be given to correct values that aresignificant abnormality prior to patients being dosed.

• Left ventricular ejection fraction measured by echocardiography ≥ 50%

Exclusion Criteria:

• Patients previously receiving treatment with histone deacetylase inhibitors (HDACi).

• Patient will need valproic acid for any medical condition during the study or within 5 days prior to the first panobinostat dose.

• Promyelocytic AML (M3).

• Secondary AML or previous history of MDS.

• Male patients whose sexual partners are women of a fertile age and do not use contraceptive.

• Known brain or leptomeningeal involvement.

• Presence of any limitation affecting the ability of the patient to comply with the treatment.

• Patients receiving any investigational agent in the 30 days prior to inclusion.

• Patient carrier of human immunodeficiency virus (HIV), hepatitis B virus surface antigen or active infection by hepatitis C virus.

• Presence of heart disorders or clinically significant heart diseases, including any of the following:

• Congenital QT prolongation "long QT syndrome").

• History or presence of sustained ventricular tachyarrhythmia (patients with a history of atrial arrhythmia are acceptable, but this must be discussed with the sponsor prior to inclusion).

• Any history of ventricular fibrillation or "torsade de pointes".

• Bradycardia defined as HR < 50 bpm. Patients with pacemakers are eligible if HR ≥ 50 bpm.

• Screening ECG with QTc > 450 msec.

• Right bundle branch block + left anterior hemiblock (bifascicular block).

• Patients with acute myocardial infarction or unstable angina ≤ 6 months before the start of the investigational drug.

• Any clinically significant heart disease (e.g., NYHA grades III or IV, or baseline LVEF <45%, uncontrolled hypertension, or history of poor compliance of antihypertensive treatment).

• Gastrointestinal disease making panobinostat absorption significantly difficult.

• Diarrhea > grade 1 according to CTCAE criteria, version 3.0.

• Any serious or uncontrolled medical condition (e.g., uncontrolled diabetes, or active or uncontrolled infection), including laboratory disorders that could involve unacceptable risks or affect protocol compliance.

• Concomitant administration of drugs with a relative risk of increasing the QT interval or inducing "torsade de pointes" if this treatment cannot be discontinued or replaced by another prior to the start of the test drug.

• Patient has active bleeding diathesis or is currently being treated with therapeutic doses of sodium warfarin (Coumadin®) or other vitamin K active agents Note: mini-dose of Coumadin® (e.g., 1 mg/day) or anti-coagulants given to maintain intravenous line patency, as well as unfractionated or low molecular weight heparin therapy is permitted

• Patients undergoing major surgery in the four weeks prior to the start of the study treatment or not recovering from the treatment adverse events.

• Patients with a history of malignancies in the past five years. Basal cell carcinoma, skin epithelioma and carcinoma of the cervix in situ are excluded.