TKI Discontinuation in CML Patients of China (TFR_china)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03251352
Recruitment Status : Recruiting
First Posted : August 16, 2017
Last Update Posted : April 24, 2018
Information provided by (Responsible Party):
Shenzhen Second People's Hospital

Brief Summary:
The primary objective of this study is to describe the maintenance of the molecular remission after tyrosine kinase inhibitor (TKI) disconnection in chronic myeloid leukaemia (CML) patients in China in the real-world clinical practice setting. This is a post-marketing, non-interventional, single-arm, prospective registry study in adult patients with chronic phase (CP) and accelerated phase (AP) in China. Patients will be recruited consecutively from the study sites during the enrollment period. The enrolled patients will be undertaking TKI discontinuation under the conditions of informed consent and frequent monitoring according to the clinical guideline.

Condition or disease
Leukemia Myelogenous Chronic BCR-ABL (Breakpoint Cluster Region-abelson Murine Leukemia) Positive

Detailed Description:
Tyrosine kinase inhibitors (TKIs) are the standard of care for patients with chronic myeloid leukaemia (CML) in chronic phase. Imatinib, the first ATP competitive TKI, received approval for use based on a dramatic and durable survival benefit. Other TKIs, the second generation compounds dasatinib, nilotinib and bosutinib and the third generation drug ponatinib, were designed and tested for a greater target-specific potency. With the development of these effective TKI treatments, CML disease burden can be reduced to minimal levels, and CML patients can have a life expectancy similar to that of the general population. Although TKI treatment may result in a deep, stable molecular remission, CML treatment guidelines recommend that patients continue TKI treatment indefinitely. However, Chronic TKI therapy can cause drug-related adverse reactions and constitute financial difficulties, which can result in decreased adherence to therapy. Therefore, the concept of a lifelong therapy with TKIs has thus been challenged and treatment-free remission (TFR) strategies will soon integrate clinical practice.TFR can be defined as the ability to maintain molecular remission without taking any TKI therapy. Studies have demonstrated the feasibility of successful TFR. In the STIM and TWISTER trials, imatinib discontinuation was proposed providing that patients had achieved deep molecular response for a certain period. The 2-year probability to maintain such deep molecular response levels without any TKI therapy was 38% in STIM and 47% in TWISTER. Subsequently, several studies were conducted and confirmed that imatinib-free remission was possible. Discontinuation of new generation TKIs was also investigated and indicated that dasatinib or nilotinib may promote access to TFR strategies as compared to imatinib. TFR is on the way to become an important goal in clinical practice, implicating an alternation in CML management guidelines in the near future.

Study Type : Observational
Estimated Enrollment : 98 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Tyrosine Kinase Inhibitor Discontinuation in Adults Patients With Chronic Myeloid Leukemia in China
Actual Study Start Date : March 1, 2017
Estimated Primary Completion Date : September 30, 2020
Estimated Study Completion Date : March 30, 2021

TKI Discontinuation Group
The enrolled patients will be undertaking TKI discontinuation under the conditions of informed consent and frequent monitoring according to the clinical guideline.

Primary Outcome Measures :
  1. Molecular Remission Rate [ Time Frame: at 12 months ]
    The molecular remission rate

Secondary Outcome Measures :
  1. Adverse Events [ Time Frame: through study completion, an average of 1 year ]
    Incidence of Treatment-free related Adverse Events

  2. Recurrence [ Time Frame: through study completion, an average of 1 year ]
    CML molecular recurrence

  3. QoL [ Time Frame: through study completion, an average of 1 year ]

Biospecimen Retention:   Samples With DNA
whole blood

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
The targeted population is CML patients under TKI treatment in China.

Inclusion Criteria:

  • Adults with CML-CP/AP and willingness of TKI discontinuation;
  • With ≥ 5 years frontline imatinib, reached MMR (major molecular response) in 2 years, with ≥ 2 years MR (molecular response) 4.5;
  • Reached MMR with frontline imatinib, with ≥ 2 years nilotinib, with ≥ 1 year MR4.5;
  • Failure with frontline imatinib, reached MMR in 1 year with nilotinib, with ≥ 2 years MR4.5;
  • With ≥ 3 years frontline imatinib, reached MMR in 1 year, with ≥ 2 years MR4.5.

Exclusion Criteria:

  • Diagnosed with CML-BP before TKI treatment;
  • With a TKI discontinuation of over 30 days in the first year;
  • With a TKI discontinuation of over 30days on average annually;
  • Reduced the dosage of TKI treatment without instructions;
  • Transferred to the second-generation TKIs after resistance to imatinib.
  • Under the treatment of stem cells transplantation

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03251352

China, Guangdong
Shenzhen Second People's Hospital Recruiting
Shenzhen, Guangdong, China, 518035
Contact: Xin Du, MD    075583366388 ext 8196   
Sponsors and Collaborators
Shenzhen Second People's Hospital

Responsible Party: Shenzhen Second People's Hospital Identifier: NCT03251352     History of Changes
Other Study ID Numbers: 201733572018022
First Posted: August 16, 2017    Key Record Dates
Last Update Posted: April 24, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Shenzhen Second People's Hospital:
TKI, CML, discontinuation

Additional relevant MeSH terms:
Neoplasms by Histologic Type