Stopping Tyrosine Kinase Inhibitors for Chronic Myeloid Leukemia

Not currently recruiting at 190 trial locations
Age: < 65
Sex: Any
Trial Phase: Phase 2
Sponsor: Children's Oncology Group
Must be taking: Tyrosine kinase inhibitors
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether patients with chronic myeloid leukemia (CML) can maintain a treatment-free remission after stopping tyrosine kinase inhibitors (TKIs). These medications control the disease by maintaining a very low level, known as molecular remission. The trial aims to determine if patients can remain in remission or regain it without continuous medication. It suits those who have been in molecular remission for at least two years and have taken TKIs for three consecutive years. Participants will stop their medication and undergo regular blood tests to monitor their condition. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, providing valuable insights into maintaining remission without medication.

Will I have to stop taking my current medications?

Yes, you will need to stop taking tyrosine kinase inhibitors (TKIs) if you join this trial, as the study is focused on observing the effects of stopping these medications.

Is there any evidence suggesting that stopping tyrosine kinase inhibitors is likely to be safe for patients with chronic myeloid leukemia?

Research shows that stopping tyrosine kinase inhibitors (TKIs) can be safe for some patients with chronic myeloid leukemia (CML) who are in a deep remission. Studies have found that patients usually tolerate TKIs well. However, only about 30% to 50% of patients qualify to stop these medications.

Long-term reviews indicate that while TKIs work effectively, they can sometimes cause side effects like skin rashes or tiredness, though serious side effects are rare. If the disease returns after stopping TKIs, patients can often resume the medication without major problems.

This trial is in phase 2, indicating that earlier studies have shown some safety, but researchers need more information to confirm this. Patients who have been taking TKIs and are considering stopping them might find this trial helpful in determining if it's a safe choice.12345

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores the possibility of stopping tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia patients who are in deep molecular remission. Unlike ongoing treatment with TKIs, this approach aims to see if patients can maintain their remission without continuous medication, which could potentially reduce long-term side effects and improve quality of life. By monitoring patients closely, researchers hope to find out if it's safe to discontinue the drugs while keeping the disease under control. This could mark a significant shift from the standard lifelong treatment approach, offering a glimpse into a more personalized and less burdensome treatment strategy.

What evidence suggests that stopping tyrosine kinase inhibitors might be an effective treatment for chronic myeloid leukemia?

Research has shown that some patients with chronic myeloid leukemia (CML) in the early stage can stop taking tyrosine kinase inhibitors (TKIs) and still control the disease without treatment. This trial will explore this approach by having participants stop taking TKIs and undergo regular monitoring. Studies have found that about 40% to 60% of patients can successfully remain in remission after stopping TKIs. Specifically, one study found that 61% of patients were free from relapse at 6 months, and 50% were relapse-free at 24 months after stopping the medication. These findings suggest that some patients can manage low levels of the disease without ongoing treatment, potentially avoiding the side effects of TKIs. While stopping TKIs doesn't work for everyone, it offers hope for many patients.26789

Who Is on the Research Team?

SC

Sonali Chaudhury

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for patients diagnosed with chronic myeloid leukemia in chronic phase (CML-CP) who were under 18 at diagnosis, have been in deep molecular remission for at least 2 years, and have taken tyrosine kinase inhibitors (TKIs) for a minimum of 3 years. Participants must be over the age of 8, able to understand English or Spanish, and not pregnant or breastfeeding. Those with certain genetic mutations or additional chromosomal abnormalities are excluded.

Inclusion Criteria

All patients and/or their parents or legal guardians must sign a written informed consent
No significant visual or motor impairment that would prevent computer use or recognition of visual test stimuli
All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
See 11 more

Exclusion Criteria

Lactating females are not eligible unless they have agreed not to breastfeed their infants
I am currently pregnant.
I am not pregnant or have confirmed it with a negative pregnancy test.
See 3 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Discontinuation

Participants stop taking TKI medication within 10 days after enrollment

10 days
1 visit (in-person)

Monitoring

Participants undergo peripheral blood collection to monitor loss of MMR every 4 weeks in year 1, every 6 weeks in year 2, and every 12 weeks in year 3

36 months
Regular visits every 4-12 weeks

Re-initiation of Treatment

Participants who lose their molecular remission may restart TKI medication and are monitored every 4 weeks in year 1, every 6 weeks in year 2, and every 12 weeks in year 3

Up to 36 months
Regular visits every 4-12 weeks

Follow-up

Participants are followed up annually after completion of study treatment

Annually

What Are the Treatments Tested in This Trial?

Interventions

  • Drug Withdrawn
  • Tyrosine Kinase Inhibitor
Trial Overview The study is examining if stopping TKI medication affects the ability to maintain or re-enter molecular remission in CML-CP patients. It involves questionnaire administration, biospecimen collection to monitor disease levels, and quality-of-life assessments after drug withdrawal.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: Basic Science (stop taking TKI, biospecimen collection)Experimental Treatment5 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials
467
Recruited
241,000+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Published Research Related to This Trial

In a study of 293 Italian patients with chronic myeloid leukemia (CML) who discontinued tyrosine kinase inhibitors (TKI) after achieving deep molecular response, 62% maintained treatment-free remission (TFR) after a median follow-up of 34 months, indicating that stopping TKI can be safe and effective.
The study found no disease progression during the follow-up period, supporting the feasibility of TKI discontinuation in clinical practice, with the majority of patients stopping treatment due to shared decision-making with their physician.
Observational study of chronic myeloid leukemia Italian patients who discontinued tyrosine kinase inhibitors in clinical practice.Fava, C., Rege-Cambrin, G., Dogliotti, I., et al.[2020]
In the LAST study involving 172 patients with chronic myeloid leukemia (CML), discontinuation of tyrosine kinase inhibitors (TKIs) was found to be safe, with 60.8% of patients achieving treatment-free remission (TFR) after stopping their medication.
Patients who discontinued TKIs reported significant improvements in quality of life, including reductions in fatigue (80.4%), depression (34.8%), and diarrhea (87.5%), highlighting the potential benefits of stopping TKIs beyond just cancer management.
Assessment of Outcomes After Stopping Tyrosine Kinase Inhibitors Among Patients With Chronic Myeloid Leukemia: A Nonrandomized Clinical Trial.Atallah, E., Schiffer, CA., Radich, JP., et al.[2022]

Citations

Tyrosine Kinase Inhibitor discontinuation in Chronic Myeloid ...Relapse‐free survival was 61% at 6 months and 50% at 24 months, with similar results in patients treated with imatinib or 2G‐TKI. Another study that evaluated ...
Estimated Savings After Stopping Tyrosine Kinase Inhibitor ...The findings indicate that an estimated $50 billion could be saved by eligible patients who attempt to stop TKI therapy.
Long-term outcomes of tyrosine kinase inhibitors in chronic ...Long-term outcomes with tyrosine kinase inhibitors (TKIs) show that their impact on chronic myeloid leukemia (CML) is sustained as shown by 13 studies with 5- ...
Discontinuation of Tyrosine Kinase Inhibitor Therapy and ...Discontinuation of TKI therapy and successful TFR can be achieved in 40% to 60% of chronic-phase CML patients. •. Limited data exist on safety and outcomes of ...
interim results from the DAstop2 trial | LeukemiaIn summary, we show that a 2nd TFR attempt after dasatinib treatment is safe, feasible and TFR rates seem in the range of those reported in ...
6.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/39486043/
Long-term outcomes of tyrosine kinase inhibitors in chronic ...Second-generation (2G) TKIs induce responses faster than IM and recognize IM-resistance mutations but do not prolong survival compared with IM.
Long-term safety review of tyrosine kinase inhibitors in ...This review summarizes the safety profiles of the currently approved TKIs and how they impact treatment selection in the first- and later-line settings of CML.
475 Asciminib (ASC) Demonstrates Favorable Safety and ...Tx-free remission is a key Tx goal, but only 30%-40% pts on IMA and 40%-50% on 2nd-generation (2G) TKIs meet discontinuation criteria. A ...
Which Is the Best Tyrosine Kinase Inhibitor for Newly ...Data from ENESTnd are from the 10-year outcome analysis, whereas data from DASISION are from the 5-year analysis. Abbreviations: CML, chronic ...
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