The Efficacy and Safety of Induction-Maintenance Protocol for Patients With Chronic Myelogenous Leukaemia

Chronic Myeloid Leukemia Clinical Trial

Official title: A Phase II Study to Determine the Efficacy and Safety of Induction-Maintenance Protocol for Patients With Chronic-Phase Chronic Myelogenous Leukaemia

Status Recruiting

Clinical Trial Summary

The purpose of this pilot study is to investigate whether some patients who were started on a 2G-TKI as first-line treatment can be safely switched to imatinib, a first-generation TKI, while maintaining or even deepening the molecular response as a cost-effective treatment. Eligible patients will be switched to imatinib 400mg daily, with regular molecular monitoring.

Clinical Trial Description

Imatinib, nilotinib and dasatinib are standard first-line options for newly diagnosed patients with chronic-phase chronic myeloid leukemia (CML). While nilotinib and dasatinib, also known as second-generation TKI (2G-TKI), have been shown to result in earlier and deeper molecular response, they have not been proven superior to imatinib in terms of clinical outcomes like progression-free survival and overall survival. Moreover, their long-term safety has been questioned: nilotinib is associated with increased cardiovascular risk while dasatinib causes pleural effusion in significant proportion of patients and may even lead to pulmonary hypertension.

The purpose of this pilot study is to investigate whether some patients who were started on a 2G-TKI as first-line treatment can be safely switched to imatinib, a first-generation TKI, while maintaining or even deepening the molecular response as a cost-effective treatment. Eligible patients will be switched to imatinib 400mg daily, with regular molecular monitoring.

In case of molecular progression

The following should be systematically performed:

• Clinical examination

• Baseline blood test including complete blood count (CBC), liver and renal function, lactate dehydrogenase (LDH), urate

• Restart the original 2G-TKI and in same dose as given before study entry unless medically indicated to change therapy

• Screening of breakpoint cluster region- Abelson murine leukemia (BCR-ABL) kinase domain mutations

• In the absence of signs of haematological relapse or breakpoint cluster region- Abelson murine leukemia (BCR-ABL1) ≥ 1% (IS ratio), bone marrow aspiration and cytogenetics are not routinely performed unless deemed indicated by the physician in charge.

The patient will be followed until major molecular response (MMR) is re-achieved and further 6 months beyond. Date of progression, hematological data at progression (molecular, cytogenetic, and hematological), and treatment proposed for molecular progression and response to it (molecular, cytogenetic, hematological) will be collected. Follow-up for overall survival (OS) and progression-free survival (PFS) will last 2 years since the date of switch of TKI.

In case of loss of complete hematological response (CHR) or any sign of accelerated or blastic phase of CML, the patient will be immediately considered as in disease progression and TKI should be started immediately. ;

Related Conditions & MeSH terms

• Chronic Myeloid Leukemia
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Chronic-Phase
• Philadelphia Chromosome
• Philadelphia Chromosome Positive CML

• NCT number: NCT03241199
• Study type: Interventional
• Source: The University of Hong Kong
• Contact: Carol Cheung, MBBS
• Phone: 852 22553111
• Email: drcarolcheung@gmail.com
• Status: Recruiting
• Phase: Phase 2
• Start date: August 1, 2017
• Completion date: January 1, 2021