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)

Overview

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.

Interventions

• Other TFR(Treatment-Free Remission)
  Withdrawal TKIs(Tyrosine kinase inhibitors: Imatinib or Flumatinib or Nilotinb or Dasatinib)

Primary outcome measures

• Deep molecular response(DMR) rate of 12 months [Time frame: The 12th month]
• Treatment-Free Remission(TFR) rate of 2 years [Time frame: The second year]

Secondary outcome measures (8)

• TFR rate [Time frame: The 6months、12months]
• DMR rate [Time frame: The 24/36/48/60 months]
• DMR persistence rate in 2 years [Time frame: 2 years]
• Disease progression rate , time to progression [Time frame: The whole study, up to 7 years]
• Loss of Major Molecular Remission(MMR-loss IS BCR-ABL≥0.1%） [Time frame: TFR phase in the study, up to 2 years]
• Re-Major Molecular Remission [Time frame: The TFR phase, up to 2 years]
• Treatment-related safety [Time frame: The whole study , up to 7 years]
• Patient Report Outcome（PRO） [Time frame: Every 3 months in the whole enrollment period, up to 7 years]

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;

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT05440747 · GDPH-CML-TFR-2020-12

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗