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

NCT05440747 | Not Yet Recruiting

• 1 other identifier: GDPH-CML-TFR-2020-12
• Study Type: observational
• Target: 203
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Chronic Myeloid Leukemia; Treatment-free Remission

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (8)

• TFR rate

  The 6months、12months

• DMR rate

  The 24/36/48/60 months

• DMR persistence rate in 2 years

  2 years

• Disease progression rate , time to progression

  The whole study, up to 7 years

• Loss of Major Molecular Remission(MMR-loss IS BCR-ABL≥0.1%）

  TFR phase in the study, up to 2 years

Other Outcomes (2)

• Clonal evolution in CML patients without optimal efficacy

  After participants loss optimal efficacy in milestone,and once a years after that, up to 7 years

• Resistant mutation rate

  The whole study, up to 7 years

Study Arms (2)

Newly diagnosed CML-CP patients

Treat with TKI (Imatinib or Flumatinib or Nilotinb or Dasatinib).

Other: TFR(Treatment-Free Remission)

Patients with suboptimal response

1. Treat with original TKI 2. Treat with original TKI combined with interferon/thymosin; 3. Replace other TKI ; 4. Replace other TKI and combined with interferon/thymosin.

Other: TFR(Treatment-Free Remission)

Interventions

TFR(Treatment-Free Remission) OTHER

Withdrawal TKIs(Tyrosine kinase inhibitors: Imatinib or Flumatinib or Nilotinb or Dasatinib)

Newly diagnosed CML-CP patients; Patients with suboptimal response

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• \) Aged \>=14 years old male and female;
• \) 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 ;
• \) Never received stem cell transplantation before enrollment;
• \) 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Guangdong Provincial People's Hospital: lead

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jianyu Jianyu, PhD

  Sponsor GmbH

  STUDY CHAIR

Central Study Contacts

Jianyu Weng, PhD

CONTACT

+86-020-83827812; gdph_wjy21@gd.gov.cn

Lisi Huang

CONTACT

+86-020-83827812; lisi_huang5413@163.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 2, 2022
• First Posted: July 1, 2022
• Study Start: July 31, 2022
• Primary Completion: October 31, 2024
• Study Completion (Estimated): October 31, 2031
• Last Updated: July 1, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR