Safety & Efficacy Study of Oral Panobinostat (LBH589) With Chemotherapy in Patients < 65 Years Old With Acute Myeloid Leukemia (AML)

A Phase Ib, Dose-finding Study of Oral Panobinostat (LBH589) in Combination With Idarubicin and Cytarabine Induction and High-dose Cytarabine-based Consolidation Therapy in Adult Patients Less Than or Equal to 65 Years Old With Acute Myeloid Leukemia (AML)

This study will be conducted to assess the maximum tolerated dose (MTD) of panobinostat given 3 times a week (administered on weeks 2 and 3 of a 4 week cycle) in combination with induction chemotherapy (idarubicin and cytarabine) in newly diagnosed patients with a cytopathologically confirmed diagnosis of high-risk AML, and to investigate the safety of the combination in this regimen.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia (AML)
• Intervention / Treatment: Drug: Panobinostat

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • Hannover, Germany, 30625
    • Novartis Investigative Site
  • Ulm, Germany, 89081
    • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08025
    • Novartis Investigative Site
  • Castilla Y Leon
    • Salamanca, Castilla Y Leon, Spain, 37007
      • Novartis Investigative Site
• United States
  • California
    • Stanford, California, United States, 94304
      • Stanford University Medical Center Stanford U
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute Beth Israel Deaconess Med Ctr
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State Comprehensive Cancer Center/James Cancer Hospital Dept.ofJamesCancerHospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina -Hollings Cancer Center MUSC/HCC (2)
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center, Clinical Trials Center Vanderbilt 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Newly diagnosed adult patients = 65 years old with a cytopathologically confirmed diagnosis of high-risk AML
• = 20% bone marrow blasts via bone marrow aspiration or biopsy
• The patient has not yet been treated for AML
• 1º or 2º AML patients with high-risk category features
• ECOG PS = 2
• Renal function and liver function limits.

Exclusion Criteria:

• Patient with a 'favorable' or 'better-risk' cytogenetic profile = t(15;17); t(8;21); or inv(16) or t(16;16)
• Patient has clinical symptoms suggestive of CNS leukemia and/or CSF findings for CNS leukemia
• Prior treatment with deacetylase inhibitors (DACi) including, panobinostat
• Impaired cardiac function
• Female patient who is pregnant or breast feeding
• Male patient who is not willing to use a barrier method of contraception

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Panobinostat	Drug: Panobinostat; Oral administration of panobinostat given 3 times a week (administered on weeks 2 and 3 of a 4 week cycle) in combination with induction chemotherapy (idarubicin and cytarabine.; Other Names: LBH589

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Define the maximum tolerated dose of Panobinostat (LBH589) that can be given with standard idarubicin and ara-C chemotherapy measured by safety and tolerability.	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
To determine the number of patients who have safety and tolerability events	1 year
To determine Panobinostat's pharmacokinetic parameters (study the amount of Panobinostat in a person's blood over time) following study treatments	1 year
To determine the response of Panobinostat (LBH589) given with standard idarubicin and ara-C chemotherapy (as defined by Cheson 2003)	1 year

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• DeAngelo DJ, Walker AR, Schlenk RF, Sierra J, Medeiros BC, Ocio EM, Rollig C, Strickland SA, Thol F, Valera SZ, Dasgupta K, Berkowitz N, Stuart RK. Safety and efficacy of oral panobinostat plus chemotherapy in patients aged 65 years or younger with high-risk acute myeloid leukemia. Leuk Res. 2019 Oct;85:106197. doi: 10.1016/j.leukres.2019.106197. Epub 2019 Aug 1.

Helpful Links

• Results for CLBH589G2101 can be found on the Novartis Clinical Trial Results Website

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (ACTUAL): May 1, 2014
• Study Completion (ACTUAL): May 1, 2014

Study Registration Dates

• First Submitted: October 17, 2010
• First Submitted That Met QC Criteria: November 16, 2010
• First Posted (ESTIMATE): November 17, 2010

Study Record Updates

• Last Update Posted (ACTUAL): December 19, 2020
• Last Update Submitted That Met QC Criteria: December 16, 2020
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: AML; bone marrow; acute leukemia; HDACi; abnormal blast cells of myeloid; cytogenetic abnormalities
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Histone Deacetylase Inhibitors; Panobinostat
• Other Study ID Numbers: CLBH589G2101; 2009-016809-42 (EUDRACT_NUMBER)