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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Myeloid Leukemia; Treatment-free Remission
• Intervention / Treatment: Other: TFR(Treatment-Free Remission)

• Study Type: Observational
• Enrollment (Anticipated): 203

Contacts and Locations

• Study Contact: Name: Jianyu Weng, PhD; Phone Number: +86-020-83827812; Email: gdph_wjy21@gd.gov.cn
• Study Contact Backup: Name: Lisi Huang; Phone Number: +86-020-83827812; Email: lisi_huang5413@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Newly diagnosed CML-CP patients; Treat with TKI (Imatinib or Flumatinib or Nilotinb or Dasatinib).	Other: TFR(Treatment-Free Remission); Withdrawal TKIs(Tyrosine kinase inhibitors: Imatinib or Flumatinib or Nilotinb or Dasatinib)
Patients with suboptimal response; 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); Withdrawal TKIs(Tyrosine kinase inhibitors: Imatinib or Flumatinib or Nilotinb or Dasatinib)

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Guangdong Provincial People's Hospital
• Investigators: Study Chair: Jianyu Jianyu, PhD, Sponsor GmbH

Study record dates

Study Major Dates

• Study Start (Anticipated): July 31, 2022
• Primary Completion (Anticipated): October 31, 2024
• Study Completion (Anticipated): October 31, 2031

Study Registration Dates

• First Submitted: April 2, 2022
• First Submitted That Met QC Criteria: June 27, 2022
• First Posted (Actual): July 1, 2022

Study Record Updates

• Last Update Posted (Actual): July 1, 2022
• Last Update Submitted That Met QC Criteria: June 27, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Other Study ID Numbers: GDPH-CML-TFR-2020-12

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: After the study was complete, IPD will be uploaded as an supplementary data of the research paper. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
• IPD Sharing Supporting Information Type: Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No