Treatment With Second Generation Tyrosine Kinase Inhibitors (2G TKI) Post Imatinib Failure Survey

Treatment With Second Generation TYROSINE KINASE INHIBITORS (2G TKI) Post Imatinib Failure: Factors Predicting Response and Predictive Value of Response

The purpose of this study is to determine predictive value of Hammersmith score on Complete Cytogenetic Response (CCyR).

Study Overview

• Status: Completed
• Conditions: Leukemia, Myeloid, Chronic-Phase (CML-CP)
• Intervention / Treatment: Drug: Imatinib

Detailed Description

Historic cohort prolonged by a 12-month follow-up period.

Prospective: look forward using periodic observations collected predominantly following subject enrollment: one year of follow up of patients with CP-CML alive at the time of the study.

Retrospective: look back using observations collected predominantly prior to subject selection and enrollment : historical data of patients with CP-CML initiated with a 2G TKIs post-imatinib failure (resistance or intolerance) between 1-Jan-2005 and 30-June-2009.

The inclusion of a historical cohort will allow a rapid enrollment of a large number of patients of this rare pathology, while the prospective follow up of this cohort would allow long term data to be obtained, including the assessment of the impact on survival and appreciate the patient's quality of life (QoL), compliance and satisfaction.

• Study Type: Observational
• Enrollment (Actual): 173

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Hematology centers (hospitals) which have necessary historical data available

Description

Patients with Additional Chromosomal Anomalies (ACA) are accepted to be in CP. Patients enrolled in open-label clinical trials or other observational trials are also allowed (unless explicitly prohibited by the trial).

This trial does not prohibit participation in other observational trials.

Inclusion Criteria:

• Patients diagnosed with CP-CML. (ACA) are allowed
• Age >18 years old
• Prior treatment with imatinib monotherapy as first line treatment, to which the patient is deemed resistant or intolerant.Patients treated by INF and/or AraC prior (but not concomitant) to imatinib are eligible.
• Initiated with a 2G TKIs post-imatinib failure (resistance or intolerance) between 1-Jan-2005 and 30-Jun-2009.

Exclusion Criteria:

• Patients in (or with history of) accelerated or blastic phase CML
• Patients treated by allogeneic stem cell transplantation.
• Any other CML treatment except for INF and/or AraC,and a short period of Hydroxyurea or Anagrelide prior to imatinib.
• Patients treated with 2G TKI for reasons other than imatinib failure.
• Patients with no historical data (e.g. possibility of Sokal Score calculation) available.
• Patients participating in clinical or observational trials which explicitly prohibit enrollment in non interventional studies.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients in CP-CML treated with 2G TKI; Patients in CP-CML treated with 2G TKI (nilotinib or dasatinib) post imatinib failure	Drug: Imatinib; Drug being observed but not provided; Other Names: Dasatinib; Nilotinob

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Predictive value of Hammersmith score on Complete Cytogenetic Response (CCyR)	The purpose of this study is to determine predictive value of Hammersmith score on Complete Cytogenetic Response (CCyR), as assessed by the following: Distribution of patients according to Hammersmith score levels; Characterization of association between Hammersmith score and occurrence of CCyR; Assessment of capacity of Hammersmith score to predict CCyR, using diagnostic test assessment methods. This score is measured at the time of imatinib failure.	CCyR at 6 month of 2GTKI treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Predictive value of Hammersmith score on Major Molecular Response (MMR)	The purpose of this study is to determine predictive value of Hammersmith score on Major Molecular Response(MMR), as assessed by the following: Distribution of patients according to Hammersmith score levels; Characterization of association between Hammersmith score and occurrence of MMR; Assessment of capacity of Hammersmith score to predict MMR, using diagnostic test assessment methods. This score is measured at the time of imatinib failure.	MMR at 3 month of 2GTKI treatment
Predictive factors of Overall survival (including Hammersmith score, MMR at 3 months and CCyR at 6 months of 2G TKI treatment together with patients, disease and treatment characteristics)		From switch to 2G TKI between 01Jan2005 and 30Jun2009 to 31Oct2011 if alive or to the death
Predictive value of Hammersmith score compared to other factors	imatinib treatment duration, mutations at time of failure, best response to imatinib, time between imatinib failure & initiation of 2G TKI on the response to 2G TKI & on the survival end points (Overall Survival (OS)& Progression Free Survival (PFS)).	From switch to 2G TKI between 01Jan2005 and 30Jun2009 to 31Oct2011 if alive or to the death
Patients populations (socio-demographic data, medical history, disease history, co morbidities treated with 2G TKI		When occurs the switch from Imatinib to 2G TKI between 01Jan2005 and 30Jun2009
Patients' satisfaction, Quality of life & compliance to treatment in patients treated with 2G TKIs		For all alive patients treated with 2G TKI during the enrolment period (Jun2010 to Oct2010)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trials Disclosure
• For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: August 24, 2010
• First Submitted That Met QC Criteria: August 24, 2010
• First Posted (Estimate): August 25, 2010

Study Record Updates

• Last Update Posted (Estimate): September 30, 2016
• Last Update Submitted That Met QC Criteria: September 28, 2016
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Imatinib Mesylate; Dasatinib
• Other Study ID Numbers: CA180-291