Acute Myeloblastic Leukaemia Clinical Trial
— PANOBIDARAOfficial title:
A Phase I/II Multicenter, National, Open-Label Study of Panobinostat in Combination With Idarubicin and Cytarabine in Patients Aged 65 Years or Older With Newly Diagnosed Acute Myeloblastic Leukaemia (AML)
Verified date | December 2018 |
Source | PETHEMA Foundation |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 46 |
Est. completion date | December 2018 |
Est. primary completion date | May 2016 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 65 Years and older |
Eligibility |
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 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 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. |
Country | Name | City | State |
---|---|---|---|
Spain | Hospital Clinic y Provincial de Barcelona | Barcelona | |
Spain | Hospital Germans Trías i Pujol | Barcelona | |
Spain | Hospital Santa Creu y Sant Pau. Barcelona | Barcelona | |
Spain | Hospital 12 de Octubre. Madrid | Madrid | |
Spain | Hospital Clínico San Carlos. Madrid | Madrid | |
Spain | Hospital Ramón y Cajal. Madrid | Madrid | |
Spain | Hospital Morales Messeguer. Murcia | Murcia | |
Spain | Hospital Univ. La Fe de Valencia | Valencia | |
Spain | Hospital Lozano Blesa. Zaragoza | Zaragoza |
Lead Sponsor | Collaborator |
---|---|
PETHEMA Foundation |
Spain,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | To establish the maximum tolerated dose (MTD) of panobinostat in combination with idarubicin and cytarabine after an induction cycle in patients aged 65 years or older with newly diagnosed AML | 1 year | ||
Primary | To analyse efficacy in terms of response to an induction (+/- reinduction) and consolidation regimens with idarubicin and cytarabine in combination with panobinostat | 2 years | ||
Primary | To explore efficacy in terms of TTR during a maintenance period with panobinostat as monotherapy in patients aged 65 years or older with newly diagnosed AML | 2 years | ||
Secondary | Investigation of the overall safety and tolerability of panobinostat when given in combination with idarubicin and cytarabine, with special focus on cardiac safety determined by echocardiography and ECG monitoring | 1 year | ||
Secondary | Survival: Overall survival, disease-free survival, and duration of response | 4 years | ||
Secondary | Impact of Panobinostat in the reduction of the minimum residual disease (MRD) monitored by multiparametric flow cytometry at different time points of the study: During the induction and consolidation treatments and during the maintenance treatment | 4 years | ||
Secondary | To investigate the safety and tolerability of panobinostat in combination with idarubicin and cytarabine and of panobinostat as monotherapy measured in terms of incidence of clinical and biological toxicity | 2 years |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT00464217 -
Treatment of the Acute Myeloblastic Leukaemia in Patients Over 65 Years
|
Phase 4 |