Study of Treatment Free Remission in Patients With Chronic Myeloid Leukemia in Chronic Phase

Study Overview
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Brief Summary
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The principal aim of this study is to evaluate complete molecular remission in patients with chronic myeloid leukemia (CML) in deep molecular response after stopping tyrosine kinase inhibitor (TKI) treatment. The second aim is to characterize the immunological status of patients with CML at the time of TKI interruption and then at 3 months after the interruption.

Detailed Description
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ARGENTINA STOP TRIAL is a multicentre, open-label, uncontrolled trial to estimate the persistence of molecular remission in patients with chronic phase Chronic Myeloid Leukemia (CML) in Deep Molecular Response after stopping Tyrosine Kinase Inhibitor (TKI) Primary Objective: - To identify the proportion of patients who continue on Major Molecular Response after discontinuing treatment with TKI. Secondary objectives: To characterize the immunological status of patients with CML at the time of interruption and then at 3 and 12 months after the interruption. Tertiary objective: To evaluate the pharmacoeconomic impact of interrupting the treatment.

Official Title
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Prospective Study of Treatment Free Remission in Patients With Chronic Myeloid Leukemia in Chronic Phase Who Achieved Deep Molecular Response With Tyrosine Kinase Inhibitors in Real Life Setting in Argentina - (Argentine Stop Trial)

Conditions
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CML

Intervention / Treatment
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* Drug: Discontinuing treatment with Tyrosine Kinase Inhibitor after enrolment


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Signed Informed consent. Patients with a diagnosis of CML BCR-ABL positive in CP treated with approved TKI (Imatinib, Nilotinib or Dasatinib) in 1st line or in 2nd line due to intolerance to the 1st line or in 2nd line due to the lack of deep MR with 1st line TKI, which never presented criteria for treatment failure. Age ≥ 18 years ≥ 4 years of treatment with imatinib, nilotinib or dasatinib. Achievement of MR 4.5 in a standardized laboratory (BCR-ABL1 IS ≤ 0.0032%). Evidence of MR 4.5 sustained for ≥ 2 years, as documented in at least 4 tests performed at least 3 months apart. Evidence of typical quantifiable BCR-ABL1 transcript (b3a2 [e14a2] and / or b2a2 [e13a2], typical isoforms of p210). Exclusion criteria: Patients who previously discontinued TKI and demonstrated recurrence of the disease. Patients with failure to any TKI at any time. Patients who presented accelerated phase or CML in blast crisis at any time. Patients with atypical transcript not quantifiable by RT qPCR BCR-ABL mutation detected at any time during the course of the resistant disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: multicentre, open-label, uncontrolled trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: CML patient TKI discontinuation study<br>Treatment free remission in patients with chronic myeloid leukemia in chronic phase who achieved deep molecular response with tyrosine kinase inhibitors | Drug: Discontinuing treatment with Tyrosine Kinase Inhibitor after enrolment<br>* Discontinuing treatment with Tyrosine Kinase Inhibitor after enrolment with a scheduled molecular monitoring until month 24.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Molecular relapse free survival during 24 months | Molecular relapse free survival, defined as the time from the start of TKI interruption until the loss of the MMR. RQ PCR (IS) >0.1% BCR ABL will be considered as loss of MMR | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-free survival during 24 months | Treatment-free survival , defined as the time from the start of TKI interruption to the restart of the TKI. | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DISCONTINUATION