Clinical trial NCT01242774: Safety & Efficacy Study of Oral Panobinostat (LBH589) With Chemotherapy in Patients < 65 Years Old With Acute Myeloid Leukemia (AML)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Myeloid Leukemia (AML)
Keywords: AML
bone marrow
abnormal blast cells of myeloid
acute leukemia
cytogenetic abnormalities
HDACi
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2010-11-17
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Define the maximum tolerated dose of Panobinostat (LBH589) that can be given with standard idarubicin and ara-C chemotherapy measured by safety and tolerability.
timeFrame: 1 year
Secondary outcomes:
measure: To determine the number of patients who have safety and tolerability events
timeFrame: 1 year
measure: To determine Panobinostat's pharmacokinetic parameters (study the amount of Panobinostat in a person's blood over time) following study treatments
timeFrame: 1 year
measure: To determine the response of Panobinostat (LBH589) given with standard idarubicin and ara-C chemotherapy (as defined by Cheson 2003)
timeFrame: 1 year
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University Medical Center Stanford U
state: California
city: Boston
country: United States
facility: Dana Farber Cancer Institute Beth Israel Deaconess Med Ctr
state: Massachusetts
city: Columbus
country: United States
facility: Ohio State Comprehensive Cancer Center/James Cancer Hospital Dept.ofJamesCancerHospital
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina -Hollings Cancer Center MUSC/HCC (2)
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center, Clinical Trials Center Vanderbilt 3
state: Tennessee
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Salamanca
country: Spain
facility: Novartis Investigative Site
state: Castilla Y Leon
city: Barcelona
country: Spain
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.