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

Chronic Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05440747
• Other study ID #: GDPH-CML-TFR-2020-12
• Status: Not yet recruiting
• Start date: July 31, 2022
• Est. completion date: October 31, 2031

Study information

• Verified date: June 2022
• Source: Guangdong Provincial People's Hospital
• Contact: Jianyu Weng, PhD
• Phone: +86-020-83827812
• Email: gdph_wjy21[@]gd.gov.cn
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 203
• Est. completion date: October 31, 2031
• Est. primary completion date: October 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Myeloid Leukemia
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Guangdong Provincial People's Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Clonal evolution in CML patients without optimal efficacy	Bone marrow karyotype analysis once a year in the patients without optimal efficacy in milestone through study completion	After participants loss optimal efficacy in milestone,and once a years after that, up to 7 years
Other	Resistant mutation rate	Molecular Mutation Examination(qPCR) once a year in patient without optimal efficacy through study completion.	The whole study, up to 7 years
Primary	Deep molecular response(DMR) rate of 12 months	DMR is defined by IS BCR-ABL/ABL achieve MR4.0(=0.01%)	The 12th month
Primary	Treatment-Free Remission(TFR) rate of 2 years	The proportion of drug withdrawal	The second year
Secondary	TFR rate	TFR rate of 6/12months,Median duration of TFR	The 6months?12months
Secondary	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
Secondary	DMR persistence rate in 2 years	DMR is defined by IS BCR-ABL/ABL achieve MR4.0	2 years
Secondary	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
Secondary	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
Secondary	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
Secondary	Treatment-related safety	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	The whole study , up to 7 years
Secondary	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