~12 spots leftby Nov 2025

TKI Cessation for Chronic Myeloid Leukemia

(TOKIN Trial)

Recruiting in Palo Alto (17 mi)
+3 other locations
MP
Overseen byMartha Mims, MD, PhD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Baylor College of Medicine
Must be taking: Tyrosine kinase inhibitors
Disqualifiers: Stem cell transplant, HIV, others
No Placebo Group
Prior Safety Data

Trial Summary

What is the purpose of this trial?

This is a single-arm, phase II study to evaluate safety and efficacy of tyrosine kinase inhibitor (TKI) cessation for chronic myeloid leukemia (CML) patients with stable molecular response in a real world population.

Will I have to stop taking my current medications?

The trial is specifically about stopping tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia, so you will need to stop taking TKIs if you participate. The protocol does not mention other medications, so it's unclear if you need to stop any other current medications.

What data supports the effectiveness of the drug Bosutinib for treating chronic myeloid leukemia?

Research shows that Bosutinib is effective for patients with chronic myeloid leukemia who are resistant or intolerant to previous treatments like Imatinib. In a study, 60% of patients achieved a major cytogenetic response by year 5, and the overall survival rate was 84% at year 5, indicating its effectiveness in managing the disease.12345

Is TKI cessation for chronic myeloid leukemia safe for humans?

Bosutinib, a type of TKI, has been shown to be generally safe for humans, with common side effects including mild gastrointestinal issues and skin rash. Serious side effects are less common and include diarrhea and rash, but these are usually manageable.23678

How is the TKI cessation treatment for chronic myeloid leukemia unique?

The TKI cessation treatment for chronic myeloid leukemia is unique because it involves stopping the use of tyrosine kinase inhibitors (TKIs) like Bosutinib, Dasatinib, and Imatinib in patients who have achieved a deep molecular response, allowing them to potentially maintain remission without ongoing medication. This approach is different from continuous TKI therapy and offers a treatment-free remission option, which is not common in other cancer treatments.2891011

Research Team

MP

Martha Mims, MD, PhD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

This trial is for adults with chronic myeloid leukemia (CML) who have been on TKI therapy for over 3 years and show a stable molecular response. They must have good blood counts, no signs of aggressive leukemia outside the bone marrow, and be expected to live more than a year without treatment. Participants need to understand the study's research nature and consent in writing.

Inclusion Criteria

Prior evidence of a quantifiable BCR-ABL1 transcript by RT-PCR
Contraception requirements will be as per routine clinical practice.
Absolute Neutrophil Count (ANC) ≥ 1.5 x 10E9/L
See 12 more

Exclusion Criteria

I have an ongoing liver condition like hepatitis or cirrhosis.
I have been diagnosed with HIV.
Any medical condition that, in the opinion of the investigator, would exclude the patient from participating in this study
See 7 more

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants continue TKI therapy for more than 36 months with a current status of complete molecular remission (CMR) before cessation

36+ months

Cessation

Participants stop taking TKI and undergo monthly BCR-ABL1 testing for 24 months

24 months
24 visits (monthly in-person)

Follow-up

Participants are monitored for progression-free survival and molecular relapse-free survival

6 months

Treatment Details

Interventions

  • Bosutinib (Tyrosine Kinase Inhibitor)
  • Dasatinib (Tyrosine Kinase Inhibitor)
  • Imatinib Mesylate (Tyrosine Kinase Inhibitor)
  • Imatinib Mesylate, Dasatinib, Nilotinib or Bosutinib Re-initiation (Drug)
  • Imatinib Mesylate, Dasatinib, Nilotinib or Bosutinib Withdrawal (Other)
  • Nilotinib (Tyrosine Kinase Inhibitor)
Trial OverviewThe study tests if patients with CML can safely stop taking their tyrosine kinase inhibitors (TKIs), which are drugs like Imatinib Mesylate, Dasatinib, Nilotinib or Bosutinib. If needed, it also looks at what happens when these drugs are restarted.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: All Subjects Enrolled (stop taking TKI)Experimental Treatment2 Interventions
Patients with a diagnosis of Philadelphia chromosome- or BCR-ABL1-positive CML (as determined by cytogenetics, FISH, or PCR), prior evidence of a quantifiable BCR-ABL1 transcript by RT-PCR, and whom have been taking TKI for \> 36 months with a current status of complete molecular remission (CMR). TKI cessation begins within 7 days of study registration. Patients undergo BCR-ABL1 test every month in 24 months.

Find a Clinic Near You

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials
1,044
Recruited
6,031,000+
Paul Klotman profile image

Paul Klotman

Baylor College of Medicine

Chief Executive Officer since 2010

MD, PhD

James Versalovic profile image

James Versalovic

Baylor College of Medicine

Chief Medical Officer since 2020

MD from Baylor College of Medicine

Findings from Research

In a phase I/II study involving 284 patients with chronic myeloid leukemia who had previously failed imatinib treatment, bosutinib showed durable efficacy, with 54% of patients remaining on treatment at 2 years and 40% at 5 years.
Bosutinib demonstrated a cumulative major cytogenetic response rate of 60% and a complete cytogenetic response rate of 50% by year 5, with manageable side effects primarily consisting of gastrointestinal issues, confirming its role as an effective second-line treatment.
Safety and efficacy of second-line bosutinib for chronic phase chronic myeloid leukemia over a five-year period: final results of a phase I/II study.Gambacorti-Passerini, C., Cortes, JE., Lipton, JH., et al.[2019]
Bosutinib shows equivalent efficacy to nilotinib and dasatinib in treating newly diagnosed chronic-phase chronic myeloid leukemia (CP-CML), based on an unanchored matching-adjusted indirect treatment comparison using patient-level data from the BFORE trial and aggregated data from other studies.
While there were no statistically significant differences in major molecular response (MMR) or disease progression between bosutinib and the other two drugs, bosutinib demonstrated a trend towards better outcomes in achieving deeper molecular responses (MR4 and MR4.5) compared to nilotinib and dasatinib after 24 months.
An indirect comparison between bosutinib, nilotinib and dasatinib in first-line chronic phase chronic myeloid leukemia.Muresan, B., Mamolo, C., Cappelleri, JC., et al.[2022]
In a phase III study involving 536 patients with newly diagnosed chronic-phase CML, bosutinib demonstrated significantly higher rates of major molecular response (47.2% vs. 36.9%) and complete cytogenetic response (77.2% vs. 66.4%) compared to imatinib after 12 months.
While bosutinib was more effective, it also had a higher incidence of gastrointestinal side effects and liver enzyme elevations, indicating a need for monitoring but suggesting it may be a strong first-line treatment option for CML.
Bosutinib Versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia: Results From the Randomized BFORE Trial.Cortes, JE., Gambacorti-Passerini, C., Deininger, MW., et al.[2022]

References

Safety and efficacy of second-line bosutinib for chronic phase chronic myeloid leukemia over a five-year period: final results of a phase I/II study. [2019]
An indirect comparison between bosutinib, nilotinib and dasatinib in first-line chronic phase chronic myeloid leukemia. [2022]
Bosutinib Versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia: Results From the Randomized BFORE Trial. [2022]
Adherence, persistence and efficacy of dasatinib and nilotinib in the treatment of patients resistant or intolerant to imatinib with chronic myeloid leukemia in chronic phase: an Italian multicenter study over two years in real life. [2022]
Bosutinib shows low cross intolerance, in chronic myeloid leukemia patients treated in fourth line. Results of the Spanish compassionate use program. [2022]
The European medicines agency review of bosutinib for the treatment of adult patients with chronic myelogenous leukemia: summary of the scientific assessment of the committee for medicinal products for human use. [2021]
[Optimizing the use of bosutinib in patients with chronic-phase chronic myeloid leukemia: Recommendations of a panel of experts from the Fi-LMC (French CML working group)]. [2023]
Bosutinib is active in chronic phase chronic myeloid leukemia after imatinib and dasatinib and/or nilotinib therapy failure. [2022]
Successful tyrosine kinase inhibitor discontinuation outside clinical trials - data from the population-based Swedish chronic myeloid leukaemia registry. [2021]
Observational study of chronic myeloid leukemia Italian patients who discontinued tyrosine kinase inhibitors in clinical practice. [2020]
11.United Statespubmed.ncbi.nlm.nih.gov
Discontinuation of dasatinib or nilotinib in chronic myeloid leukemia: interim analysis of the STOP 2G-TKI study. [2022]