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.

Overall Study

Imatinib Mesylate

Protein Kinase Inhibitors

Randomized Cohort: Adapted strategy of dosage of Imatinib Mesylate : 600mg/d po

Randomized Cohort: Standard strategy of dosage of Imatinib Mesylate : 400mg/d po

Parallel Cohort: Standard strategy of dosage of Imatinib Mesylate : 400mg/d po

Imatinib Mesylate 600 MG Oral Tablet

Imatinib Mesylate 400 MG Oral Tablet

ETIENNE Gabriel, MD

The Imatinib Mesylate at a dose of 400 mg / day is the standard treatment for patients with CML-CP. Recent studies show that the quality of response rate (complete cytogenetic response and major molecular response rate) is dependent on the residual plasma Imatinib.

The Imatinib Mesylate at a dose of 400 mg / day is the standard treatment for patients with CML-CP. Recent studies show that the quality of response rate (complete cytogenetic response and major molecular response rate) is dependent on the residual plasma Imatinib. This study aims to evaluate the effectiveness of a strategy for dose adjustment of Imatinib Mesylate based on the measurement of the residual plasma imatinib in patients treated for at least 2 years Imatinib 400 mg / d in complete cytogenetic response for at least 1 year.

IM concentration \< 1000ng/mL Randomized Cohort : "adapted strategy" versus "standard strategy" / IM concentration \>= 1000ng/mL Parallel Cohort: "standard strategy"

Phase III Trial Evaluating the Effectiveness of a Dose Adjustment of Imatinib Mesylate on the Molecular Response

Phase III Trial Evaluating the Effectiveness of a Dose Adjustment of IM on the Molecular Response in Patients With LMC in Chronic Phase Treated With IM 400 mg / Day for at Least Two Years, Complete Cytogenetic Response for at Least One Year

The BCR-ABL transcript rate was analysed by molecular biology by RQ-PCR at study entry, 3 months, 6 months, 9 months and 12 months.

Treatment is considered effective at 12 months if:

* for patients with an inclusion transcript rate less than 0.1%: the transcript rate at 12 months is less or equal to 0.001% or undetectable.
* for patients with an inclusion transcript rate greater than 0.1% : the transcript rate at 12 months is less or equal to 0.1% or undetectable.

If BCR-ABL transcript level was unavailable at M12, the treatment was considered ineffective.

The BCR-ABL transcript rate was analysed by molecular biology by RQ-PCR at study entry, 3 months, 6 months, 9 months and 12 months.

Efficacy was also evaluated at 3, 6, 9 and 12 months in terms of decreasing the rate of BCR-ABL transcripts of 2 logarithms, relative to the initial value (inclusion). The lack of data on the transcript rate was considered as failure (no decrease).

The molecular response is defined by the measurement of BCR-ABL transcript rate by quantitative RT-PCR (RQ-PCR) on peripheral venous blood according to international standards.

It is defined as:

* Major Molecular Response (MMR): BRC-ABL transcript rate ≤ 0.1%
* Complete Molecular Response (CMR): transcript BCR-ABL undetectable and non quantifiable.

Time to complete molecular response was defined by the time from inclusion/randomization and the first CMR.

The BCR-ABL transcript rate was analysed by molecular biology by RQ-PCR at study entry, 3 months, 6 months, 9 months and 12 months.

The BCR-ABL transcript rate was analysed by molecular biology by RQ-PCR at study entry, 3 months, 6 months, 9 months and 12 months.

Time to the first BCR-ABL undetectable was defined by the time from inclusion/randomization and the first CMR.

Overall survival is defined by the time from de date of inclusion/randomization to the date of death (of any cause).

Progression-free survival was defined by the time from the date of inclusion and the date of progression.

Progression was defined as :

* Death,
* Passage into the acceleration phase defined by one of the following criteria: % of blood or medullary blasts greater than 15% but less than 30%, blasts plus promyelocytes greater than 30% in the blood or marrow, basophils greater than 20% in the blood, thrombocytopenia less than 100x10\^9/L unrelated to treatment, clonal evolution)
* Passage to the blast transformation phase defined by one of the following criteria: % of blasts of blood or bone marrow greater than 30%, occurrence of extramedullary damage other than histologically proven hepato-splenic.
* Increase in BCR-ABL transcripts greater than or equal to 2-log compared to the previous values (this increase must be confirmed within 3 months).

Novartis

Institut Bergonié

All adverse envent (related and unrelated to treatment) were reported.

All serious adverse envent (related and unrelated to treatment) were reported.

Randomized Cohort: Adapted strategy of dosage of Imatinib Mesylate : 600mg/d po

Imatinib Mesylate 600 MG Oral Tablet: Imatinib Mesylate for CP CML

Imatinib 600 (Randomized Trial)

Randomized Cohort: Standard strategy of dosage of Imatinib Mesylate : 400mg/d po

Imatinib Mesylate 400 MG Oral Tablet: Imatinib Mesylate for CP CML

Imatinib 400 (Randomized Trial)

Parallel Cohort: Standard strategy of dosage of Imatinib Mesylate : 400mg/d po

Imatinib Mesylate: Imatinib Mesylate for CP CML

Imatinib400 (Parallel Cohort)

Total

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

France

Region of Enrollment

All patients included, regardless of whether or not treatment was administered, and regardless violations of any eligibility criteria. This population corresponds to Intention to treat population for randomized study, and population assessable for the primary endpoind for the parralel cohort.

Pr Simone Mathoulin-Pelissier

Percentage of Patients Presenting a Decline of the BCR-ABL Transcript Rate at 12 Months From Baseline - Randomised Study

3 months

6 months

9 months

12 months

Rate of Decline of 2-log of the BCR-ABL Transcript Rate at 3 ,6, 9 and 12 Months From Baseline - Randomised Study

3 months - CMR

3 months : MMR

6 months : CMR

6 months : MMR

9 months : CMR

9 months : MMR

12 months : CMR

12 months : MMR

Molecular Response at 3, 6, 9 and 12 Months

Time to Complete Molecular Response (CMR) and Major Molecular Response (MMR)

Rate of BCR-ABL Undetectable

Time to the First BCR-ABL Undetectable

Overall Survival

Progression-free Survival

Imatinib400 (Cohort)

Philadelphia Chromosome

Translocation, Genetic

Chromosome Aberrations

Non-Interventional

Bristol-Myers Squibb

Observational medical record review of newly diagnosed CML-CP participants in China

Study of Chinese Newly Diagnosed Participants With Philadelphia Chromosome-Positive (Ph+) Chronic Myeloid Leukemia in Chronic Phase (CML-CP)

Treatment Pattern, Clinical Outcome and Healthcare Resource Utilization Associated With Chinese Newly Diagnosed Patients With Philadelphia Chromosome-Positive (Ph+) Chronic Myeloid Leukemia in Chronic Phase (CML-CP): A Retrospective Observational Study

Complete Cytogenetic Response (CCyR): 0% Ph+ cells in metaphase in bone marrow (BM)

Major molecular response (MMR) is defined as 3-log reduction in International Scale of BCR-ABL mRNA

Including health insurance and comorbid conditions

Dasatinib

Flumatinib

Flumatinib 600mg QD orally form 1 to 12 months

Dasatinib 100mg QD orally form 1 to 12 months

Xin Du

Xin Du, MD

The purpose of this study is to explore the efficacy and safety of switching to flumatinib versus dasatinib after imatinib-related low-grade adverse events in patients with chronic myeloid leukemia in chronic phase (CML-CP) in China. This is a post-marketing, interventional, double-arm, prospective, open-label, randomized controlled study in CML-CP patients in China. Patients will be recruited consecutively from the study sites during the enrollment period. The enrolled patients will be given flumatinib or dasatinib under the conditions of informed consent and frequent monitoring according to the clinical guideline.

The Efficacy and Safety of Switching to Flumatinib Versus Dasatinib After Imatinib-related Low-grade Adverse Events in CML-CP Patients

The Efficacy and Safety of Switching to Flumatinib Versus Dasatinib After Imatinib-related Low-grade Adverse Events in Patients With Chronic Myeloid Leukemia in Chronic Phase: an Randomized Controlled Trial.

Shenzhen Second People's Hospital

Asciminib

MAP requests are initiated by a licensed physician.https:// www.novart is.com/healthcare-professionals/managed-access-programs

The purpose of this registration form is to list all Managed Access Programs (MAPs) related to ABL001, asciminib

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Efficacy and Safety of LBH589 in Adult Patients With Refractory Chronic Myeloid Leukemia (CML) in Chronic Phase	NCT00451035	Chronic Myeloid...	LBH589	18 Years -	Novartis
Phase III Trial Evaluating the Effectiveness of a Dose Adjustment of Imatinib Mesylate on the Molecular Response	NCT01827930	Leukemia, Myelo...	Imatinib Mesyla... Imatinib Mesyla... Imatinib Mesyla...	18 Years -	Institut Bergonié
Study of Chinese Newly Diagnosed Participants With Philadelphia Chromosome-Positive (Ph+) Chronic Myeloid Leukemia in Chronic Phase (CML-CP)	NCT03509896	Chronic Myeloid... Philadelphia Ch... Chronic Myeloid...	Non-Interventio...	18 Years -	Bristol-Myers Squibb
The Efficacy and Safety of Switching to Flumatinib Versus Dasatinib After Imatinib-related Low-grade Adverse Events in CML-CP Patients	NCT04933526	Chronic Myeloid...	Flumatinib Dasatinib	18 Years -	Shenzhen Second People's Hospital
Phase III Trial Evaluating the Effectiveness of a Dose Adjustment of Imatinib Mesylate on the Molecular Response	NCT01827930	Leukemia, Myelo...	Imatinib Mesyla... Imatinib Mesyla... Imatinib Mesyla...	18 Years -	Institut Bergonié
Efficacy and Safety of LBH589 in Adult Patients With Refractory Chronic Myeloid Leukemia (CML) in Chronic Phase	NCT00451035	Chronic Myeloid...	LBH589	18 Years -	Novartis
Study of Chinese Newly Diagnosed Participants With Philadelphia Chromosome-Positive (Ph+) Chronic Myeloid Leukemia in Chronic Phase (CML-CP)	NCT03509896	Chronic Myeloid... Philadelphia Ch... Chronic Myeloid...	Non-Interventio...	18 Years -	Bristol-Myers Squibb
Managed Access Programs for ABL001, Asciminib	NCT04360005	Chronic Myeloid...	Asciminib	18 Years - 99 Years	Novartis

Spots Global Cancer Trial Database for chronic myeloid leukemia in chronic phase