Follow-up Study on Chronic Myeloid Leukemia Patients Achieving Treatment-free Remission

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Myeloid Leukemia, BCR/ABL-Positive

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

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Wen-Chien Chou, MD. PhD.; Phone Number: 265997 +886-2312-3456; Email: wchou@ntu.edu.tw

Study Locations

• Taiwan
  • Taipei, Taiwan, 10002
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Wen-Chien Chou, MD. PhD.; Phone Number: 265997 +886-2312-3456; Email: wchou@ntu.edu.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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

Description

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.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of patients who were in major molecular response (MMR) without re-initiation of treatment	Real-time quantitative polymerase chain reaction (RT-qPCR) would be done to determined the transcript level of BCR-ABL fusion gene in peripheral blood samples	at week 48 of tyrosine kinase inhibitor (TKI) discontinuation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of patients who were in MR4.5 (BCR-ABL transcript level ⩽0.0032% IS) and off treatment	Real-time quantitative polymerase chain reaction (RT-qPCR) would be done to determined the transcript level of BCR-ABL fusion gene in peripheral blood samples	at week 48 of TKI discontinuation
Treatment-free survival		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
The proportion of patients who reachieved of MMR after TKI restart	Real-time quantitative polymerase chain reaction (RT-qPCR) would be done to determined the transcript level of BCR-ABL fusion gene in peripheral blood samples	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).
The proportion of patients who reachieved of MR4.5 after TKI restart	Real-time quantitative polymerase chain reaction (RT-qPCR) would be done to determined the transcript level of BCR-ABL fusion gene in peripheral blood samples	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).
Incidence and severity of treatment-related adverse events [Safety and Tolerability]	Adverse events (AEs) would be assessed according to the CTCAE v4.03	Evaluation of AEs would be conducted on an ongoing basis on study until 30 days after the last day of TFR

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2022
• Primary Completion (Anticipated): August 11, 2028
• Study Completion (Anticipated): August 11, 2032

Study Registration Dates

• First Submitted: June 15, 2022
• First Submitted That Met QC Criteria: June 26, 2022
• First Posted (Actual): June 30, 2022

Study Record Updates

• Last Update Posted (Actual): September 7, 2022
• Last Update Submitted That Met QC Criteria: September 5, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Chronic myeloid leukemia; Treatment free remission
• 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
• Other Study ID Numbers: 202202074RINB

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No