Real-World Disease Management and Outcomes in Chronic Myeloid Leukaemia

Chronic myeloid leukaemia (CML) diagnosis is based on the demonstration of a BCR-ABL fusion transcript expressed by the Philadelphia (Ph) chromosome by RQ-PCR and/or the demonstration of t(9;22)(q34;q11) by conventional karyotyping or interphase FISH. As per standard practice, response to therapy is monitored using either molecular or cytogenetic tests or both; specifically, patients are monitored by quantitative PCR on peripheral blood, supplemented by bone marrow karyotyping if it was clinically indicated. ABL kinase mutational analysis is carried out when the transcript ratio has increased over two sequential samples or on clinical demand. Testing for T315I mutation is also performed for patients who fail to respond to first line TKI and all patients who acquire TKI resistance over the course of their treatment.

Data collection is initiated six months after date of diagnosis; research nurses working to agreed operating procedures and data standards visit each of the 14 hospitals in the region and abstract a core clinical dataset from the patients' medical records. The information collected includes demographic details, baseline blood count data and first line treatment. All details are abstracted onto structured forms and entered onto the web-based system, which integrates Haematological Malignancy Research Network (HMRN) and Haematological Malignancy Diagnostic Service (HMDS) data. An important feature of data acquisition is the emphasis on primary source information; data from radiology reports, blood tests, clinical examination, and clinician summaries are recorded, enabling embedded algorithms in the database system to automatically generate stage and prognostic scores. Further data abstraction from the medical records has been undertaken to capture information on subsequent treatment lines. Information on date and cause of death were obtained from the National Health Service (NHS) Central Register.

Study Overview

• Status: Completed
• Conditions: Chronic Myeloid Leukaemia

• Study Type: Observational
• Enrollment (Actual): 555

Contacts and Locations

Study Locations

• United Kingdom
  • York, United Kingdom
    • Haematological Malignancy Research Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This was a retrospective, noninterventional cohort study

Description

Inclusion Criteria:

• Adult (18+ years) patients newly diagnosed with CML in chronic phase (ICD-O-3: 9875/3) by HMDS between 1st September, 2004 to 31st August, 2019 whilst resident in the HMRN region and treated within the Network.

Exclusion Criteria:

None specified.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of patients who received tyrosine kinase inhibitors (TKIs), by treatment llne	Up to 18 years
Year treatment started, by TKI	Up to 18 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with response to TKIs	Disease response was defined as either a major molecular response (MMR, ≤ 0.1% BCR-ABL1) or as an MR2, which is a molecular response (MR, ≤ 1.0% BCR-ABL1), or complete cytogenetic remission (CCyR).	Up to 12 months
Time to response to TKIs		Up to 12 months
Reason for switching TKI		Up to 12 months
Number of patients tested for T315I mutation by treatment line		Up to 12 months
Overall survival (OS)	OS was defined as the time (in years) from initiation of treatment (i.e., the index date) to death (any cause).	Up to 10 years
Progression-free survival	PFS was defined from the initiation of treatment (i.e., the index date) to the earliest documentation of disease progression to accelerated phase/blast crisis (AP/BC) or date of death from any cause.	Up to 10 years
Time to treatment discontinuation		Up to 10 years
Relative survival by treatment line	Relative survival (RS) was estimated to examine the CML-specific mortality rate. The Stata program strel (v1.2.7) was used to estimate RS and corresponding 95% Confidence Intervals (95%CI); with age and sex-specific background mortality rates being obtained from national life tables.	Up to 10 years

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2021
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): June 30, 2021

Study Registration Dates

• First Submitted: May 17, 2023
• First Submitted That Met QC Criteria: June 7, 2023
• First Posted (Actual): June 8, 2023

Study Record Updates

• Last Update Posted (Actual): June 8, 2023
• Last Update Submitted That Met QC Criteria: June 7, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Chronic Disease; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Other Study ID Numbers: CABL001AGB01