Treatment Free Remission (TFR) in CML Patients （CML-CP）Study

Study Overview
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Brief Summary
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Improving the quality of life and achieving Treatment-Free Remission(TFR) is a long-term goal of treatment in CML-CP patients, and deep molecular response (DMR) is necessary to achieve TFR. Cording to the historical literature, it is reported that patients with CML-CP take MMR as the therapeutic target, and the acquisition rate of DMR under long-term TKI treatment is 50%. The 2-year success rate of TFR patients was 50%. Therefore, maybe only 25% of patients with CML can successfully stop the drug for a long time. It cannot meet the withdrawal needs of patients with long-term drug survival. This study is to design a real-world observational registration study for optimal effect. On the premise of taking DMR as the target decision, through initial treatment intervention, improve the DMR rate, which will promote clinical practice, so as to improve the 2-year TFR rate of cml-cp patients. This study is a multicenter, observational, prospective registry to identify the optimal treatment for achieving TFR in CML patients. In this study, the investigators will assess the deep molecular response after 12 months of treatment and the 2-year treatment-free remission rate (TFR 2y) after drug discontinuation. Eligible participants with CML-CP can be enrolled. The observation period of all participants is at least 60 months, of which the first 36 months is the shortest treatment period, and the last 24 months is the TFR observation period after TKIs (Imatinib/Flumatinib/Nilotinb/ Dasatinib) withdrawal. During the treatment phase, participants can receive TKIs ± IFN (or other treatments) as first-line/second-line treatment, and the treatment plan will be adjusted according to the molecular response. Patients should accept TKI treatment for at least 3 years or more, and MR4/MR4.5 should achieve at least 2 years before discontinuation.

Official Title
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A Multicenter, Observational Register Study of Treatment Free Remission in Patients With Chronic Myeloid Leukemia (CML-CP)

Conditions
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Chronic Myeloid Leukemia, Treatment-free Remission

Intervention / Treatment
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* Other: TFR(Treatment-Free Remission)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1) Aged >=14 years old male and female; 2) Patients with Ph+ CML-CP should meet any of the following conditions; Newly diagnosed Patients with CML-CP; The CML-CP patients who treated with TKI (Imatinib, Nilotinib, Dasatinib and Flumatinib) are not achieved optimal （BCR-ABLIS>10% in 3 months, BCR-ABLIS>1% in 6 months, BCR-ABLIS>0.1% in 12 months or BCR-ABLIS>0.01% in 24 months ）or intolerance to these TKIs; The definition of the confirmed diagnosis: Bone marrow cytogenetics Ph chromosome t(9;22) positive and/or BCR-ABL fusion gene positive by FISH, and/or BCR-ABL fusion gene positive(>10%) by Q-PCR ; 3) Never received stem cell transplantation before enrollment; 4) Female patients with fertility have a negative pregnancy test (within 7 days before enrollment). All Patients with TFR requeirement should provid written informed consent before enrollment. Exclusion Criteria: T315I mutation is known; Received stem cell transplantation before enrollment; With other malignant tumors and need active intervention; Those who are unable to follow the protocol steps or follow up on time; Eastern Cooperative Oncology Group physical performance score (ECOG PS) >=3; Other situations deemed unsuitable by the researcher.

Ages Eligible for Study
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Minimum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Newly diagnosed CML-CP patients<br>Treat with TKI (Imatinib or Flumatinib or Nilotinb or Dasatinib). | Other: TFR(Treatment-Free Remission)<br>* Withdrawal TKIs(Tyrosine kinase inhibitors: Imatinib or Flumatinib or Nilotinb or Dasatinib)<br>|
| Patients with suboptimal response<br>Treat with original TKI Treat with original TKI combined with interferon/thymosin; Replace other TKI ; Replace other TKI and combined with interferon/thymosin. | Other: TFR(Treatment-Free Remission)<br>* Withdrawal TKIs(Tyrosine kinase inhibitors: Imatinib or Flumatinib or Nilotinb or Dasatinib)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Deep molecular response(DMR) rate of 12 months | DMR is defined by IS BCR-ABL/ABL achieve MR4.0(≤0.01%) | The 12th month | 
| Treatment-Free Remission(TFR) rate of 2 years | The proportion of drug withdrawal | The second year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TFR rate | TFR rate of 6/12months，Median duration of TFR | The 6months、12months | 
| DMR rate | DMR rate of 24/36/48/60 months, Median duration of DMR, DMR is defined by IS BCR-ABL/ABL achieve MR4.0 | The 24/36/48/60 months | 
| DMR persistence rate in 2 years | DMR is defined by IS BCR-ABL/ABL achieve MR4.0 | 2 years | 
| Disease progression rate , time to progression | Time and proportion from diagnosis to disease progression to AP or BC | The whole study, up to 7 years | 
| Loss of Major Molecular Remission(MMR-loss IS BCR-ABL≥0.1%） | Time and proportion from discontinuation to loss of MMR in TFR phase up to 2 years. | TFR phase in the study, up to 2 years | 
| Re-Major Molecular Remission | Time and proportion from restarting therapy after MMR-lose to obtain MMR through TFR phase. | The TFR phase, up to 2 years | 
| Treatment-related safety | Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | The whole study , up to 7 years | 
| Patient Report Outcome（PRO） | EORTCQLQ-CML-24 survey every 3 months in the whole enrollment period | Every 3 months in the whole enrollment period, up to 7 years |