Clinical trial NCT05440747: Treatment Free Remission (TFR) in CML Patients （CML-CP）Study
Official title: A Multicenter, Observational Register Study of Treatment Free Remission in Patients With Chronic Myeloid Leukemia (CML-CP)
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Chronic Myeloid Leukemia
Treatment-free Remission
Lead sponsor: Guangdong Provincial People's Hospital
Sponsor class: OTHER
First posted: 2022-07-01
Enrollment: 203
Sex: ALL
Minimum age (years): 14
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The participants should older than 14 years old, and Newly diagnosed with CML-CP or had been 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.

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 1) Aged \>=14 years old male and female;
* 2) Patients with Ph+ CML-CP should meet any of the following conditions;

  1. Newly diagnosed Patients with CML-CP;
  2. 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:

1. T315I mutation is known;
2. Received stem cell transplantation before enrollment;
3. With other malignant tumors and need active intervention;
4. Those who are unable to follow the protocol steps or follow up on time;
5. Eastern Cooperative Oncology Group physical performance score (ECOG PS) \>=3;
6. Other situations deemed unsuitable by the researcher.

Primary outcomes:
measure: Deep molecular response(DMR) rate of 12 months
timeFrame: The 12th month
measure: Treatment-Free Remission(TFR) rate of 2 years
timeFrame: The second year
Secondary outcomes:
measure: TFR rate
timeFrame: The 6months、12months
measure: DMR rate
timeFrame: The 24/36/48/60 months
measure: DMR persistence rate in 2 years
timeFrame: 2 years
measure: Disease progression rate , time to progression
timeFrame: The whole study, up to 7 years
measure: Loss of Major Molecular Remission(MMR-loss IS BCR-ABL≥0.1%）
timeFrame: TFR phase in the study, up to 2 years
measure: Re-Major Molecular Remission
timeFrame: The TFR phase, up to 2 years
measure: Treatment-related safety
timeFrame: The whole study , up to 7 years
measure: Patient Report Outcome（PRO）
timeFrame: Every 3 months in the whole enrollment period, up to 7 years
Other outcomes:
measure: Clonal evolution in CML patients without optimal efficacy
timeFrame: After participants loss optimal efficacy in milestone,and once a years after that, up to 7 years
measure: Resistant mutation rate
timeFrame: The whole study, up to 7 years
Locations:
Study officials:
affiliation: Sponsor GmbH
name: Jianyu Jianyu, PhD
role: STUDY_CHAIR
References: