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

NCT00840346 | Completed Phase 1 DMC

• 1 other identifier: PANOBIDARA
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 9

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 with idarubicin and cytarabine and in monotherapy in patients with newly-diagnosed AML aged 65 years or older.

Conditions

Acute Myeloblastic Leukaemia

Keywords

Acute Myeloblastic Leukaemia (AML); Panobinostat

Outcome Measures

Primary Outcomes (3)

• 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

• To analyse efficacy in terms of response to an induction (+/- reinduction) and consolidation regimens with idarubicin and cytarabine in combination with panobinostat

  2 years

• 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 Outcomes (4)

• 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

• Survival: Overall survival, disease-free survival, and duration of response

  4 years

• 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

• 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

Study Arms (1)

1

EXPERIMENTAL

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

Interventions

panobinostat DRUG

20 mg, 30 mg, 40 mg in combination with idarubicin and cytarabine, according to the classical 3+3 schedule.

1

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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%

You may not qualify if:

• 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.
• 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").
• 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.

Sponsors & Collaborators

• PETHEMA Foundation: lead

Study Sites (9)

Hospital Clinic y Provincial de Barcelona

Barcelona, Spain

Location

Hospital Germans Trías i Pujol

Barcelona, Spain

Location

Hospital Santa Creu y Sant Pau. Barcelona

Barcelona, Spain

Location

Hospital 12 de Octubre. Madrid

Madrid, Spain

Location

Hospital Clínico San Carlos. Madrid

Madrid, Spain

Location

Hospital Ramón y Cajal. Madrid

Madrid, Spain

Location

Hospital Morales Messeguer. Murcia

Murcia, Spain

Location

Hospital Univ. La Fe de Valencia

Valencia, Spain

Location

Hospital Lozano Blesa. Zaragoza

Zaragoza, Spain

Location

Related Publications (1)

• Ocio EM, Herrera P, Olave MT, Castro N, Perez-Simon JA, Brunet S, Oriol A, Mateo M, Sanz MA, Lopez J, Montesinos P, Chillon MC, Prieto-Conde MI, Diez-Campelo M, Gonzalez M, Vidriales MB, Mateos MV, San Miguel JF; PETHEMA Group. Panobinostat as part of induction and maintenance for elderly patients with newly diagnosed acute myeloid leukemia: phase Ib/II panobidara study. Haematologica. 2015 Oct;100(10):1294-300. doi: 10.3324/haematol.2015.129577. Epub 2015 Jul 9.

  PMID: 26160880 DERIVED

Related Links

• Spanish Association of Hematology
• CRO

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Panobinostat

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 7, 2009
• First Posted: February 10, 2009
• Study Start: September 1, 2009
• Primary Completion: May 1, 2016
• Study Completion: December 1, 2018
• Last Updated: December 11, 2018

Record last verified: 2018-12

Locations

ES (9)