Nilotinib in Newly Diagnosed Adult Philadelphia Chromosome and /or BCR-ABL Positive Chronic Myeloid Leucaemia in Chronic Phase (ENEST1st)

Overview
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This study will assess the efficacy and safety of nilotinib in adult patients with newly diagnosed Philadelphia chromosome positive/BCR-ABL positive chronic myeloid leukaemia in chronic phase. The aim of the study is to confirm the rates of complete molecular remission (CMR) of nilotinib in newly diagnosed CML chronic phase patients in a pan-European population using the EUTOS standardized laboratories.

SEEK ID: https://cgnbonn.fdm.digital-medicine.org/projects/11

Public web page: Not specified

Organisms: No Organisms specified

NFDI4Health PIs: Cristoph Scheid

Trial Project start date: 5th Jul 2010

Trial Project end date: 1st Jul 2014

Extended Metadata (Nfdi4Health MDS 3.3)

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Id of the project(*) : 29547

Resource classification(*)

Type of the resource : Study

Title(s)/name(s) of the Project

Title/name : Nilotinib in Newly Diagnosed Adult Philadelphia Chromosome and /or BCR-ABL Positive Chronic Myeloid Leucaemia in Chronic Phase (ENEST1st)
Language of the title/name : English

Title/name : A Phase IIIb, Multicentre, Open-label Study of Nilotinib in Adult Patients With Newly Diagnosed Philadelphia Chromosome and/or BCR-ABL Positive CML in Chronic Phase
Language of the title/name : English

Acronym(s) of the Project

Acronym : ENEST1st
Language of the acronym : English

Description(s) of the Project

Description : This study will assess the efficacy and safety of nilotinib in adult patients with newly diagnosed Philadelphia chromosome positive/BCR-ABL positive chronic myeloid leukaemia in chronic phase. The aim of the study is to confirm the rates of complete molecular remission (CMR) of nilotinib in newly diagnosed CML chronic phase patients in a pan-European population using the EUTOS standardized laboratories.
Language of the description : English

Keyword(s) describing the Project

Keyword(*) : Leukemia

Keyword(*) : myeloid

Keyword(*) : myelogenous

Keyword(*) : chronic BCR-ABL positive

Keyword(*) : Nilotinib

Keyword(*) : Philadelphia chromosome

Keyword(*) : CML in chronic phase

Contributor(s) of the Project

Is it a personal or organisational contribution?(*) : Personal
Details about the contributing organisation(s)/institution(s)/group(s)
Contributor type(*) : Not specified
Funding identifier(s) : Not specified
Name of the organisation/institution/group(*) : Not specified
Details about the contributing person(s)
Contributor type(*) : Principal investigator
Given name(*) : Cristoph
Family name(s)(*) : Scheid
Digital identifier(s)
Identifier(*) : 0009-0007-6539-226X
Scheme(*) : ORCID
Email address : christoph.scheid@uk-koeln.de
Phone number : Not specified
Organisation(s) associated with the contributor
Name(*) : Klinik I für Innere Medizin, University Hospital Cologne
Address : Uniklinik Köln, Kerpener Straße 62, 50937 Köln
Web page : https://innere1.uk-koeln.de/
Digital identifier(s)
Identifier(*) : 05mxhda18
Scheme(*) : ROR

Is it a personal or organisational contribution?(*) : Personal
Details about the contributing organisation(s)/institution(s)/group(s)
Contributor type(*) : Not specified
Funding identifier(s) : Not specified
Name of the organisation/institution/group(*) : Not specified
Details about the contributing person(s)
Contributor type(*) : Contact
Given name(*) : Andreas
Family name(s)(*) : Zueiter
Digital identifier(s)
Identifier(*) : Not specified
Scheme(*) : Not specified
Identifier(*) : Not specified
Scheme(*) : Not specified
Email address : Not specified
Phone number : Not specified
Organisation(s) associated with the contributor
Name(*) : Klinik I für Innere Medizin, University Hospital Cologne
Address : Uniklinik Köln, Kerpener Straße 62, 50937 Köln
Web page : https://innere1.uk-koeln.de/
Digital identifier(s)
Identifier(*) : 05mxhda18
Scheme(*) : ROR
Identifier(*) : Not specified
Scheme(*) : Not specified
Name(*) : Not specified
Address : Not specified
Web page : Not specified
Digital identifier(s)
Identifier(*) : Not specified
Scheme(*) : Not specified
Identifier(*) : Not specified
Scheme(*) : Not specified

Is it a personal or organisational contribution?(*) : Organisational
Details about the contributing organisation(s)/institution(s)/group(s)
Contributor type(*) : Sponsor (primary)
Funding identifier(s) : Not specified
Name of the organisation/institution/group(*) : Novartis Pharma GmbH
Details about the contributing person(s)
Contributor type(*) : Not specified
Given name(*) : Not specified
Family name(s)(*) : Not specified
Digital identifier(s)
Identifier(*) : Not specified
Scheme(*) : Not specified
Identifier(*) : Not specified
Scheme(*) : Not specified
Email address : Not specified
Phone number : Not specified
Organisation(s) associated with the contributor
Name(*) : Novartis Pharma GmbH
Address : Not specified
Web page : https://www.novartis.com/de-de/
Digital identifier(s)
Identifier(*) : Not specified
Scheme(*) : Not specified
Identifier(*) : Not specified
Scheme(*) : Not specified
Name(*) : Not specified
Address : Not specified
Web page : Not specified
Digital identifier(s)
Identifier(*) : Not specified
Scheme(*) : Not specified
Identifier(*) : Not specified
Scheme(*) : Not specified

Alternative identifiers

Type of the registry(*) : NCT (ClinicalTrials.gov)
Identifier(*) : NCT01061177

Characteristics of the Project

Is it an interventional or non-interventional Project? : Interventional
Specification of the type of the Project
Interventional Project type : Parallel
Non-interventional Project type : []
Primary health condition(s) or disease(s) considered in the Project
Primary health condition or disease name(*) : Leukemia, Myeloid, Chronic-Phase
Terminology/classification(*) : MeSH
Code of the health condition or disease : D015466
Groups of diseases or conditions(*)
Which groups of diseases or conditions were the data collected on? : Neoplasms (II)
On which diseases or conditions were the data collected? : []
Collects mortality data? : Not specified
Administrative information about the Project
Status of the ethics committee approval : Not specified
Overall Project status : Completed: Recruitment, data collection, and data quality management completed normally
Participants enrolled by invitation? : Not specified
Start date : 5 July 2010
End date : Not specified
Mono- or multicentric? : Multicentric
Number of centers : 321
One or more data providers? : Not specified
Number of data providers : Not specified
Primary subject(*) : Person
Eligibility criteria for Project participants
Eligibility criteria: Minimum age
Minimum eligible age(*) : 18
Unit of age(*) : Years
Eligibility criteria: Maximum age
Maximum eligible age(*) : 99
Unit of age(*) : Years
Eligible gender : Not applicable
Inclusion criteria : - Patients with diagnosis of CP-CML with cytogenetic confirmation of Philadelphia (Ph) chromosome; - Ph negative cases or patients with variant translocations who are BCR-ABL positive in multiplex PCR are also eligible; - WHO performance status 0-2; - Laboratory assessments within normal Limits; - Written informed consent prior to any study procedures being performed
Exclusion criteria : - Known impaired cardiac function; - History of acute or chronic pancreatitis; - Impaired gastrointestinal function or disease that may alter the absorption of study drug; - Concomitant medications with potential QT prolongation, or known to interact with CYP450 isoenzymes (CYP3A4, CYP2C9, and CYP2C8); - Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy; - Patients who are pregnant or breast feeding, or females of reproductive potential not employing an effective method of birth control. Female patients must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug
Population of the Project(*)
Coverage : International
Country(ies) : Germany, France, Spain, United Kingdom
Region(s) and/or city(ies) : Not specified
Interventions of the Project
Name of the intervention(*) : Nilotinib
Type of the intervention : Drug (including placebo)
Additional information about the intervention : This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily. Nilotinib was supplied by Novartis as 150 mg hard gelatin capsules in bottles. Nilotinib was dosed on a flat scale and not dosed by body weight. This form of supply was continued for all participants entered into the core study. Other Names: AMN107
Name(s) of the arm(s) associated with the given intervention : Experimental: Nilotinib
Exposures of the Project
Name of the exposure : Not specified
Type of the exposure : Not specified
Additional information about the exposure : Not specified
Name(s) of the group(s) associated with the given exposure : Not specified
Outcome measures in the Project
Name of the outcome measure(*) : Percentage of Participants With Molecular Response (MR4^0) at 18 Months
Description of the outcome measure : MR4^0 was defined as either (i) detectable disease ≤ 0.01% BCR-ABL ratio (international scale (IS)) with mean ABL transcripts ≥ 10 000 or (ii) undetectable disease in complementary deoxyribonucleic acid (cDNA) with ≥ 10 000 ABL transcripts.
Type of the outcome measure : Primary
Time point(s) of assessment : at 18 months
Name of the outcome measure(*) : Percentage of Participants Free From Progression to Accelerated Phase/Blast Crisis (AP/BC) at 12 and 24 Months
Description of the outcome measure : The following events were considered disease progression to AP/BC: Death due to disease under study; AP, as defined by any of the following: ≥ 15% blasts in the peripheral blood or bone marrow, but < 30% blasts in both the peripheral blood and bone marrow, ≥ 30% blasts plus promyelocytes in peripheral blood or bone marrow, ≥ 20% basophils in the peripheral blood, Thrombocytopenia (< 100 × 109/L) that was unrelated to therapy, Evidence of clonal evolution, as determined by medical review with consensus of the SSMC/DMC. BC was defined as: ≥ 30% blasts in peripheral blood or bone marrow, Appearance of extramedullary involvement other than hepatosplenomegaly proven by biopsy.
Type of the outcome measure : Secondary
Time point(s) of assessment : at 12 and 24 months
Name of the outcome measure(*) : Rate of Event Free Survival at 12 and 24 Months
Description of the outcome measure : EFS was defined as the time from the date of Day 1 (first treatment) + 1 day to the first occurrence of any of the following: Loss of complete hematologic response (CHR), Loss of CCyR, Death from any cause, Progression to the AP or BC of CML, Not achieving CHR up to 3 months (ie, 91 + 15 days), Not achieving CCyR up to 18 months (ie, 548 + 15 days), whichever is earlier.
Type of the outcome measure : Secondary
Time point(s) of assessment : at 12 and 24 months
Name of the outcome measure(*) : Percentage of Participants With Major Molecular Response (MMR) at, as Well as by, 12 and 24 Months
Description of the outcome measure : MMR was defined as BCR-ABL ratio (IS) ≤ 0.1% in a peripheral blood sample. BCR-ABL1 is an abnormal gene found in chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL). The chromosomal defect in the Philadelphia chromosome is a translocation, in which parts of two chromosomes, 9 and 22, swap places. The result is that a fusion gene is created by juxtapositioning the Abl1 gene on chromosome 9 to a part of the BCR ("breakpoint cluster region") gene on chromosome 22. Depending upon the breakpoints on the BCR gene, there are several forms of fusion proteins.
Type of the outcome measure : Secondary
Time point(s) of assessment : at 12 and 24 months
Name of the outcome measure(*) : Percentage of Participants With Complete Cytogenetic Response (CCyR) at, as Well as by, 12 and 24 Months
Description of the outcome measure : CCyR parameters were defined as 0% Philadelphia positive (Ph+) metaphases. Loss of CCyR was defined as a patient exceeding the CCyR criteria (ie, > 0% Ph+ metaphases) at a subsequent visit after the patient had achieved CCyR.
Type of the outcome measure : Secondary
Time point(s) of assessment : 12 and 24 months
Name of the outcome measure(*) : Percentage of Participants With Major Cytogenetic Response (MCyR) at, as Well as by, 12 and 24 Months
Description of the outcome measure : Major cytogenetic response (MCyR) parameters were defined as 0 to 35% Philadelphia positive (Ph+) metaphases.
Type of the outcome measure : Secondary
Time point(s) of assessment : 12 and 24 months
Name of the outcome measure(*) : Percentage of Participants Free From Progression to AP/BC With MR4^0 at 12 Months
Description of the outcome measure : The following events were considered disease progression to AP/BC: Death due to disease under study; AP, as defined by any of the following: ≥ 15% blasts in the peripheral blood or bone marrow, but < 30% blasts in both the peripheral blood and bone marrow, ≥ 30% blasts plus promyelocytes in peripheral blood or bone marrow, ≥ 20% basophils in the peripheral blood, Thrombocytopenia (< 100 × 109/L) that was unrelated to therapy, Evidence of clonal evolution, as determined by medical review with consensus of the SSMC/DMC. BC was defined as: ≥ 30% blasts in peripheral blood or bone marrow, Appearance of extramedullary involvement other than hepatosplenomegaly proven by biopsy.
Type of the outcome measure : Secondary
Time point(s) of assessment : at 12 months
Name of the outcome measure(*) : Percentage of Participants With Event Free Survival in Participants Achieving MR4^0 at 12 Months
Description of the outcome measure : EFS was defined as the time from the date of Day 1 (first treatment) + 1 day to the first occurrence of any of the following: Loss of complete hematologic response (CHR), Loss of CCyR, Death from any cause, Progression to the AP or BC of CML, Not achieving CHR up to 3 months (i.e. 91 + 15 days).
Type of the outcome measure : Secondary
Time point(s) of assessment : at 12 months
Name of the outcome measure(*) : Percentage of Participants With Progression Free Survival (PFS) at 12 and 24 Months
Description of the outcome measure : PFS was defined by the study protocol as the time from the date of start of study drug to the date of earliest progression to AP/BC, or the date of death from any cause.
Type of the outcome measure : Secondary
Time point(s) of assessment : 12 months, 24 months
Name of the outcome measure(*) : Rate of Molecular Response (MR4^0) at, as Well as by, 12 and 24 Months
Description of the outcome measure : MR4^0 was defined as either (i) detectable disease ≤ 0.01% BCR-ABL ratio (international scale (IS)) with mean ABL transcripts ≥ 10 000 or (ii) undetectable disease in complementary deoxyribonucleic acid (cDNA) with ≥ 10 000 ABL transcripts.
Type of the outcome measure : Secondary
Time point(s) of assessment : 12 months, 24 months
Name of the outcome measure(*) : Rate of Molecular Response (MR4^5) at, as Well as by, 12 and 24 Months
Description of the outcome measure : MR4^5 was defined as either (i) detectable disease ≤ 0.0032% BCR-ABL ratio (IS) with mean ABL transcripts ≥ 32 000 or (ii) undetectable disease in cDNA with ≥ 32 000 ABL transcripts).
Type of the outcome measure : Secondary
Time point(s) of assessment : 12 and 24 months
Name of the outcome measure(*) : Rate of Complete Hematologic Response (CHR) at, as Well as by, 12 and 24 Months
Description of the outcome measure : CHR was defined as all of the following present for ≥ 4 weeks in the peripheral blood: WBC count < 10 x 109/L, Platelet count < 450 x 109/L, No circulating peripheral blood blasts, promyelocytes, myelocytes, or metamyelocytes in the peripheral blood, The presence of < 5% basophils, No evidence of disease-related symptoms and extramedullary disease, including spleen and liver. Loss of CHR was defined as the appearance of any of the following after having achieved a CHR confirmed by a second determination ≥ 4 weeks later (unless associated with progression to AP/BC or death, which was considered to be a confirmed loss of CHR event on its own): WBC count that increased to > 20.0 x 109/L, Platelet count that increased to ≥ 600 x 109/L, Any palpable spleen, defined as size of spleen below costal margin > 5 cm, Appearance of > 5% myelocytes plus metamyelocytes, or any promyelocytes or blasts in the peripheral blood.
Type of the outcome measure : Secondary
Time point(s) of assessment : 12 months, 24 months
Name of the outcome measure(*) : Percentage of Participants With Overall Survival at 12 and 24 Months
Description of the outcome measure : OS was defined as the time between the date of Day 1 (first treatment) and the date of death from any cause. Deaths which occurred after the 24-month time window and which were occasionally reported by some Investigators were excluded from the analysis. This is in agreement with the protocol stating that patients were to be followed for survival and progression to AP/BC up to 24 months after the participants treatment start.
Type of the outcome measure : Secondary
Time point(s) of assessment : 12 months, 24 months
Name of the outcome measure(*) : Rate of Molecular Response (MR4^0) by 18 Months
Description of the outcome measure : MR4^0 was defined as either (i) detectable disease ≤ 0.01% BCR-ABL ratio (international scale (IS)) with mean ABL transcripts ≥ 10 000 or (ii) undetectable disease in complementary deoxyribonucleic acid (cDNA) with ≥ 10 000 ABL transcripts. BCR = Breakpoint Cluster Region gene/BCR gene product BCR-ABL is fusion gene formed from the ABL gene from chromosome 9 fusing with the BCR gene on chromosome 22, the gene product is BCR-ABL tyrosine kinase
Type of the outcome measure : Secondary
Time point(s) of assessment : by 18 months
Name of the outcome measure(*) : Rate of Molecular Response (MR4^5) by 18 Months
Description of the outcome measure : MR4^5 was defined as either (i) detectable disease ≤ 0.0032% BCR-ABL ratio (IS) with mean ABL transcripts ≥ 32 000 or (ii) undetectable disease in cDNA with ≥ 32 000 ABL transcripts). BCR = Breakpoint Cluster Region gene/BCR gene product BCR-ABL is fusion gene formed from the ABL gene from chromosome 9 fusing with the BCR gene on chromosome 22, the gene product is BCR-ABL tyrosine kinase
Type of the outcome measure : Secondary
Time point(s) of assessment : by 18 months
Name of the outcome measure(*) : Percentage of Participants With Progression Free Survival in Participants Achieving MR4^0 at 12 Months
Description of the outcome measure : PFS was defined by the study protocol as the time from the date of start of study drug to the date of earliest progression to AP/BC, or the date of death from any cause.
Type of the outcome measure : Secondary
Time point(s) of assessment : 12 months
Additional information about the Project : Not specified
Additional assessments/measurements in the Project : []
Data sharing strategy of the Project(*)
Is it planned to share the data?(*) : No, there is no plan to make data available
Supporting documents available in addition to the data : []
When and for how long will the data be available? : Not specified
Criteria for data access : Not specified
Additional information about data sharing : Not specified
DataSHIELD/Opal infrastructure available? : Not specified
Link to data request application : Not specified
Web page with additional information about data sharing : Not specified
Record linkage possible? : Not specified
Non-interventional aspects of the Project
Temporal design : []
Target follow-up duration of the Project
Target follow-up duration(*) : Not specified
Unit of time(*) : Not specified
Number of follow-ups conducted : Not specified
Biosamples retained in a biorepository : []
Specific types of retained biosamples : Not specified
Interventional aspects of the Project
Numerical phase : Phase-4
Masking of intervention(s) assignment
Masking implemented? : false
Who is masked? : []
Additional information about masking : Not specified
Type of allocation of participants to an arm : Not applicable (for single-arm trials)
Off-label use of a drug product : Not specified

Nilotinib in Newly Diagnosed Adult Philadelphia Chromosome and /or BCR-ABL Positive Chronic Myeloid Leucaemia in Chronic Phase (ENEST1st)

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