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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by:
PETHEMA Foundation
ClinicalTrials.gov Identifier:
NCT00840346
First received: February 7, 2009
Last updated: April 2, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Acute Myeloblastic Leukaemia
Drug: panobinostat
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official 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)

Resource links provided by NLM:


Further study details as provided by PETHEMA Foundation:

Primary Outcome Measures:
  • 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 [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • To analyse efficacy in terms of response to an induction (+/- reinduction) and consolidation regimens with idarubicin and cytarabine in combination with panobinostat [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Survival: Overall survival, disease-free survival, and duration of response [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 46
Study Start Date: September 2009
Estimated Study Completion Date: December 2014
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
The first patients enrolled in the trial will be successively distributed into three cohorts of patients for each dose level of panobinostat (20 mg, 30 mg, 40 mg) in combination with idarubicin and cytarabine, according to the classical 3+3 schedule
Drug: panobinostat
20 mg, 30 mg, 40 mg in combination with idarubicin and cytarabine, according to the classical 3+3 schedule.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00840346

Locations
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 Ramón y Cajal. Madrid
Madrid, Spain
Hospital 12 de Octubre. Madrid
Madrid, Spain
Hospital Clínico San Carlos. Madrid
Madrid, Spain
Hospital Morales Messeguer. Murcia
Murcia, Spain
Hospital Univ. La Fe de Valencia
Valencia, Spain
Hospital Lozano Blesa. Zaragoza
Zaragoza, Spain
Sponsors and Collaborators
PETHEMA Foundation
  More Information

Additional Information:
No publications provided

Responsible Party: Josep Mª Ribera/Executive Secretary, PETHEMA
ClinicalTrials.gov Identifier: NCT00840346     History of Changes
Other Study ID Numbers: PANOBIDARA
Study First Received: February 7, 2009
Last Updated: April 2, 2014
Health Authority: Spain: Ministry of Health

Keywords provided by PETHEMA Foundation:
Acute Myeloblastic Leukaemia (AML)
Panobinostat

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Panobinostat
Idarubicin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Histone Deacetylase Inhibitors

ClinicalTrials.gov processed this record on August 21, 2014