Neoplasms

Blood and Lymph Conditions

All Conditions

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Leukemia, Myeloid, Chronic-Phase

Neoplasms by Histologic Type

Hematologic Diseases

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Myeloid Leukemia

Chronic Graft Versus Host Disease

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Tyrosine Kinase Inhibitors

Panobinostat

Histone Deacetylase Inhibitors

Enzyme Inhibitors

Tyrosine

Participants were administered panobinostat 20 milligram (mg) orally once a day (OD) three times a week as part of a 4 week (28 day) treatment cycle. Panobinostat were administered at the same time each morning with 8oz/240 milliliter (ml) of water after a fasting period of at least two hours (water was allowed). Participants could continue treatment until they experienced unacceptable toxicity or disease progression.

LBH589

Novartis Pharmaceuticlas

This study will evaluate the efficacy and safety of LBH589B in adult patients with chronic phase chronic myeloid leukemia with resistant disease following treatment with at least two BCR-ABL tyrosine kinase inhibitors

Efficacy and Safety of LBH589 in Adult Patients With Refractory Chronic Myeloid Leukemia (CML) in Chronic Phase

A Phase II, Multicentre Study of Oral LBH589 in Patients With Chronic Phase Chronic Myeloid Leukemia With Resistant Disease Following Treatment With at Least Two Fusion Gene of the BCR and ABL Genes (BCR-ABL) Tyrosine Kinase Inhibitors

The CyR, based on the percentage of Ph+ metaphases by karyotype analysis on a bone marrow aspirate, was ideally assessed from a minimum of 20 metaphases in each bone marrow sample. The CyR was defined as: major response including complete (CCyR; 0% Ph+ metaphases) or partial (PCyR; 1 to 35% Ph+ metaphases), minor (36 to 65% Ph+ metaphases), minimal (66 to 95% Ph+ metaphases) or none (96 to 100% Ph+ metaphases).

The duration of response was defined as the time between the first documented response to the date of discontinuation due to progressive disease (PD) or death.

CHR was defined by meeting all criteria: white blood cell count \< 10 x 109/L, platelet count \< 450 x 109/L, myelocytes and metamyelocytes in peripheral blood \< 5%, basophils in peripheral blood ≤ 5%, no myeloblasts or promyelocytes in peripheral blood, and no evidence of extramedullary involvement.

Cytogenetic response was assessed by bone marrow assessment based on the percentage of Ph+ metaphases by karyotype analysis on a bone marrow aspirate, was ideally assessed from a minimum of 20 metaphases in each bone marrow sample.

Molecular response was defined as major (≤ 0.1% on the International Scale) and complete \[absence of fusion gene of the BCR and ABL genes (BCR-ABL) on an quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay with a sensitivity of at least 4.5 logs below baseline\].

BCR-ABL messenger ribose nucleic acid (mRNA) expression (molecular response) was performed by quantitative polymerase chain reaction (qPCR) and mutational analysis was performed by direct sequencing technology, and both analyses were performed by Genzyme.

Progression-free survival time is defined as the time from the treatment start to the first documentation of the disease progression or the date of death, whichever occurs first

Cmax is defined as the Maximum (peak) plasma drug concentration after single dose administration. Cmax will be reported in units of nanogram/milliliter (ng/ML).

Time to reach peak or maximum plasma drug concentration following drug administration. Tmax will be reported in units of hour (hr).

Area under the curve (AUC) is defined as the area under concentration-time curve as a measure of drug exposure. The area under the plasma concentration-time curve from time zero to 24 hours.

Clast is defined as the Last observed (quantifiable) plasma concentration at last sampling time.

Time of last sampling point. Tlast will be reported in units of hr

QTc monitoring was performed on specified days (Cycle1: Day1, 5 and 26), as well as a single pre-dose ECG once weekly during Cycle1: Week2 and Week3, Cycle2, and all subsequent cycles. Patient eligibility was ensured by a screening QTcF interval calculated by eResearchTechnology(eRT) prior to the baseline assessments. Treatment decisions were based on QTc determined by the automated reading at the investigational site (commonly used the Bazett's correction,QTcB) or measured and calculated by trained personnel at the site. Dosing relied on the investigator's assessment of the 6 baseline ECGs (the average of the 6pre-dose QTc intervals) performed prior to Cycle1/Day1 dosing, of the 3pre-dose ECGs during Cycle1:Day5 and 26, and of the single pre-dose ECGs performed once weekly for the remaining weeks of Cycle1 and subsequent cycles. The Baseline and Change From Baseline to Extreme Value QTcF interval for analysis was calculated by eRT based on the 6 baseline ECGs obtained on Cycle1/Day1.

Adverse events (AEs) are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events (SAEs) are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.

Novartis Pharmaceuticals

Safety population consisted of all patients who received at least one dose of study medication and had one valid post-baseline assessment.

Participants were administered panobinostat 20 mg orally OD three times a week as part of a 4 week (28 day) treatment cycle. Treatment were administered at the same time each morning with 240 ml of water after a fasting period of at least two hours (water was allowed). Participants could continue treatment until they experienced unacceptable toxicity or disease progression.

Participants were administered panobinostat 20 mg orally OD three times a week as part of a 4 week (28 day) treatment cycle. Panobinostat were administered at the same time each morning with 240 ml of water after a fasting period of at least two hours (water was allowed). Participants could continue treatment until they experienced unacceptable toxicity or disease progression.

Panobinostat (LBH589)

Age, Continuous

Sex: Female, Male

Caucasian

Black

Asian

Race/Ethnicity, Customized

The Full Analysis Set (FAS) consisted of all enrolled participants who have received at least one dose of study medication.

Study Director

Full Analysis Set (FAS) consisted of all enrolled participants who have received at least one dose of study medication. The outcome measure was not achieved as the study was terminated due to insufficient clinical efficacy in the targeted participants population. Due to insufficient data, this outcome could not be measured.

Major (Complete/Partial) Cytogenetic Response (MCyR) Rate

The FAS consisted of all enrolled participants who have received at least one dose of study medication. The outcome measure was not achieved as the study was terminated due to insufficient clinical efficacy in the targeted participants population. Due to insufficient data, this outcome could not be measured.

Duration of Major (Complete/Partial) Cytogenetic Response (MCyR) Rate

Complete Hematologic Response (CHR) Rate

Complete Cytogenetic Response (CCyR) and Overall (Complete/Partial/Minor/Minimal) Cytogenetic Response (OCyR) Rates

Major (MMR) and Complete (CMR) Molecular Response Rates

BCR-ABL Mutations of Participants at Study Entry and, in Responding Participants and at the Time of Disease Progression

Progression Free Survival Time

The analysis was performed on Pharmacokinetic (PK) population, defined as all participants who provide at least one post-dose PK plasma sample. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.

Maximum Plasma Concentration (Cmax) of Panobinostat

The analysis was performed on PK population, defined as all participants who provide at least one post-dose PK plasma sample. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.

Time to Peak Concentration (Tmax) of Panobinostat

Area Under the Plasma Concentration (AUC0-24) of Panobinostat

Last Observed Plasma Concentration (Clast) of Panobinostat

The analysis was performed on PK population, defined as all participants who provide at least one post-dose PK plasma sample. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point

Time of Clast (Tlast) of Panobinostat

Baseline

Change from Baseline

Participants were administered panobinostat 20 mg orally OD three times a week as part of a 4 week (28 day) treatment cycle. Treatment were administered at the same time each morning with 240 milliliter (ml) of water after a fasting period of at least two hours (water was allowed). Participants could continue treatment until they experienced unacceptable toxicity or disease progression.

The analysis was performed on Safety population consisted of all participants who had received at least one dose of study medication and had one valid post-baseline assessment.

QT Interval (QTc) in Participants Receiving Oral Panobinostat at Baseline and Change From Baseline to Extreme Value

SAEs

Deaths

AEs leading to discontinuation

Safety and Tolerability Profile of Oral Panobinostat

Participants were administered panobinostat 20 milligram (mg) orally once a day (OD) three times a week as part of a 4 week (28 day) treatment cycle. Panobinostat were administered at the same time each morning with 240 milliliter (ml) of water after a fasting period of at least two hours (water was allowed). Participants could continue treatment until they experienced unacceptable toxicity or disease progression.

Spots Global Cancer Trial Database for Efficacy and Safety of LBH589 in Adult Patients With Refractory Chronic Myeloid Leukemia (CML) in Chronic Phase

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial