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

NCT ID: NCT03241199

Last Updated: 2017-08-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-01
• Study Completion Date: 2021-01-01

Brief 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.

Detailed 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.

Conditions

Chronic Myeloid Leukemia; Philadelphia Chromosome Positive CML

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Imatinib Mesylate

imatinib 400mg daily

Group Type: EXPERIMENTAL

Imatinib Mesylate

Intervention Type: DRUG

a first-generation tyrosine kinase inhibitors

Interventions

Imatinib Mesylate

a first-generation tyrosine kinase inhibitors

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Adult (aged 18 years or above) patients diagnosed with chronic-phase CML

2. Must have received a 2G-TKI (nilotinib or dasatinib) as first-line therapy for at least 12 months (Note: Cytoreductive agents, namely hydroxyurea and anagrelide, prior to the use of TKI are allowed.)

3. In sustained, good molecular response (i.e. molecular response (MR3) or below) for at least 6 months, as confirmed with at least 2 consecutive quantitative real time-polymerase chain reaction (RT-PCR) results

Exclusion Criteria

1. Under 18 years old

2. Adults under law protection or without ability to consent

3. Previous or planned autologous/allogeneic haematopoietic stem cell transplantation

4. Documented kinase domain mutation

5. A change to the current TKI because of unsatisfactory response to a previous TKI (Note: patients are still considered eligible if the switch in TKI was due to intolerance or side effects)

6. History of disease progression (accelerated or blast phase)

7. Patients who can speak neither Chinese nor English

8. Any molecular result during the preceding 6 months that is higher than MR3, i.e. BCR-ABL1/ABL1 ratio >0.1% on IS ratio

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Professor Yok-lam Kwong

Chair Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Carol Cheung, MBBS

Role: PRINCIPAL_INVESTIGATOR

Queen Mary Hospital, Hong Kong

Locations

The University of Hong Kong

Hong Kong, , Hong Kong

Site Status: RECRUITING

Countries

Hong Kong

Central Contacts

Carol Cheung, MBBS

Role: CONTACT

drcarolcheung@gmail.com

852 22553111 ext. 3456

Crosby Lu, MMedSc

Role: CONTACT

khlu@hku.hk

852 22553111 ext. 1654

Facility Contacts

Carol Cheung, MBBS

Role: primary

drcarolcheung@gmail.com

852 22553111 ext. 3456

Crosby Lu, MMedSc

Role: backup

khlu@hku.hk

852 22553111 ext. 1654

Other Identifiers

QMH-CML-002

Identifier Type: -

Identifier Source: org_study_id