Clinical trial NCT05439889: Follow-up Study on Chronic Myeloid Leukemia Patients Achieving Treatment-free Remission
Official title: Follow-up Study on Chronic Myeloid Leukemia Patients Achieving Treatment-free Remission
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Chronic Myeloid Leukemia, BCR/ABL-Positive
Keywords: Chronic myeloid leukemia
Treatment free remission
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2022-06-30
Enrollment: 100
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adults with CP-CML and are regularly followed up at National Taiwan University Hospital (NTUH) or at the branch hospitals of the NTUH healthcare system

Brief summary: In recent years, the goal of stopping drug therapy, also known as treatment-free remission (TFR), is emerging as one of the management goals of chronic myeloid leukemia (CML) therapy. Because there is no available data on Asian patients with CML undergoing tyrosine kinase inhibitor discontinuation (TKI), the investigators plan to recruit chronic phase CML patients with deep treatment response and good medical compliance in Taiwan to evaluate the feasibility, safety and clinical consequences of TKI discontinuation.

Detailed description: 1. Primary goal: To evaluate the feasibility, safety and clinical consequences of TKI discontinuation in chronic phase CML(CP-CML) patients with deep treatment response and good medical compliance in Taiwan

2. Molecular response monitoring:

1. After discontinuation of TKI therapy, participants will receive monthly molecular monitoring of BCR-ABL transcript levels by real-time quantitative polymerase chain reaction (RT-qPCR) for one year, every two months for the second year and every three months thereafter.
2. If loss of major molecular response (MMR) (BCR-ABL transcript level ⩽ 0.1% IS) is detected at any time point post TKI discontinuation, the participant should receive repeated testing within two weeks. If loss of MMR is confirmed, TKI should be resumed within four weeks
3. RT-qPCR of BCR-ABL would be ordered every four weeks until MR4 (BCR-ABL transcript level ⩽ 0.01% IS) is re-established, and then every 12 weeks indefinitely.
4. For patients who fails to achieve MMR again within three months after TKI is re-initiated, BCR-ABL kinase domain mutation testing would be performed

Eligibility criteria: Inclusion Criteria:

1. The participant should be an adult (age ⩾20 years) with CP-CML.
2. The BCR-ABL fusion should be in the form of either e13a2 or e14a2 (p210)
3. The participant should not have documented resistance to a 2nd-generation TKI (Nilotinib or Dasatinib)
4. The participant should have received ≥ 5 years of consecutive treatment with imatinib, or ≥ 4 years of consecutive treatment with a 2nd-generation TKI (Nilotinib or Dasatinib)
5. The participant should have achieved MR4.5 (BCR-ABL ⩽0.0032% IS) or undetectable disease in the peripheral blood or bone marrow, for ≥ 2 years, which is documented on ≥ 4 separate tests performed ≥ 3 months apart.
6. Access to a reliable qPCR-based BCR-ABL test with a sensitivity of detecting of at least MR4.5.

Exclusion Criteria:

1. After evaluation, the participant is deemed to be ineligible by the investigator of this study.
2. The participant has no intention to be recruited into this study.

Primary outcomes:
measure: The proportion of patients who were in major molecular response (MMR) without re-initiation of treatment
timeFrame: at week 48 of tyrosine kinase inhibitor (TKI) discontinuation
Secondary outcomes:
measure: The proportion of patients who were in MR4.5 (BCR-ABL transcript level ⩽0.0032% IS) and off treatment
timeFrame: at week 48 of TKI discontinuation
measure: Treatment-free survival
timeFrame: From the start of TKI discontinuation until the earliest occurrence of any of the following: loss of MMR, restart of TKI for any reason, progression to accelerated phase/blast phase, or death of any cause, assessed up to 60 months
measure: The proportion of patients who reachieved of MMR after TKI restart
timeFrame: qPCR of BCR-ABL would be checked every four weeks until MR4 is re-established, and then every 12 weeks until study completion (week 240).
measure: The proportion of patients who reachieved of MR4.5 after TKI restart
timeFrame: qPCR of BCR-ABL would be checked every four weeks until MR4 is re-established, and then every 12 weeks until study completion (week 240).
measure: Incidence and severity of treatment-related adverse events [Safety and Tolerability]
timeFrame: Evaluation of AEs would be conducted on an ongoing basis on study until 30 days after the last day of TFR
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
References: