Status:
COMPLETED
Panobinostat in Combination With Idarubicin and Cytarabine in Patients Aged 65 Years or Older With Newly Diagnosed Acute Myeloblastic Leukaemia (AML)
Lead Sponsor:
PETHEMA Foundation
Conditions:
Acute Myeloblastic Leukaemia
Eligibility:
All Genders
65+ years
Phase:
PHASE1
PHASE2
Brief 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 ...
Detailed Description
A phase Ib will be initially performed to establish the MTD of panobinostat that can be administered in combination with the classic regimen of idarubicin and cytarabine in patients aged 65 years or o...
Eligibility Criteria
Inclusion
- 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 are \<LLN. Post-correction values must not be deemed to be a clinically significant abnormality prior to patients being dosed.
- Left ventricular ejection fraction measured by echocardiography ≥ 50%
Exclusion
- 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.
Key Trial Info
Start Date :
September 1 2009
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 1 2018
Estimated Enrollment :
46 Patients enrolled
Trial Details
Trial ID
NCT00840346
Start Date
September 1 2009
End Date
December 1 2018
Last Update
December 11 2018
Active Locations (9)
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1
Hospital Clinic y Provincial de Barcelona
Barcelona, Spain
2
Hospital Germans Trías i Pujol
Barcelona, Spain
3
Hospital Santa Creu y Sant Pau. Barcelona
Barcelona, Spain
4
Hospital 12 de Octubre. Madrid
Madrid, Spain