Discontinuation Study of Imatinib in Adult CP CML Patients Who Have a Complete Molecular Response to Imatinib

Study Overview
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Brief Summary
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This prospective study is performed to identify safer and more concrete indicators of successful discontinuation and explore contributing factors for sustained undetectable transcript

Detailed Description
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Imatinib (IM) treatment has been the standard of care for chronic phase (CP) chronic myeloid leukemia (CML) and approximately 50% of CP CML patients who received IM treatment achieve complete molecular response (CMR) at 6-7 years.(Hochhaus A et al. Leukemia 2009;23:1054-1061, Hughes et al. Blood 2008;112:334) The recent data from a study aimed to assess whether IM can be discontinued in patients with a CMR lasting at least 2 years showed the probability of persistent CMR at 12 months was 41%, and suggested IM can be safely discontinued, at least in some patients with sustained CMR. (Mahon et al. Lancet Oncol 2010;11:1029-1035) However, to define whether discontinuation of IM treatment can be safely employed, further validation and much longer follow-up are needed. Aims This prospective study is performed to identify safer and more concrete indicators of successful discontinuation and explore contributing factors for sustained undetectable transcript. Primary Objective: To evaluate the probability of persistent undetectable molecular residual disease (UMRD) and MR4.5 at 12 months after discontinuation To measure the duration of persistent UMRD and MR4.5 after discontinuation To identify contributing factors for sustained undetectable transcript Secondary Objective: To evaluate the probability of major molecular response (MMR) loss To evaluate the time taken to lose MMR at 12 months after discontinuation In patients with loss of MMR, the probability of re-achieving MMR/MR4.5 To measure the time taken to re-achieve MMR/MR4.5 after IM resumption To identify contributing factors for sustained re-achieve MMR/MR4.5 Trial Design This is a prospective, multicenter, non-randomised IM discontinuation study. Response Evaluation After discontinuation, molecular response was monitored using RQ-PCR assay every month up to 6 month follow-up, every 2 months up to 12 month follow-up, and every 3 months thereafter. The loss of MMR, MR4.5, and UMRD were defined on 2 consecutive assessments. If loss of MMR occurred, IM treatment was re-introduced. Written informed consents were obtained for all patients

Official Title
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A Multi-center Study of the Discontinuation of Imatinib in Adult Patients With Ph+ CML in CP Who Have a Complete Molecular Response to Imatinib

Conditions
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Chronic Myeloid Leukemia, Imatinib, Complete Molecular Response

Intervention / Treatment
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* Behavioral: Imatinib treatment discontinuing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult (≥ 18 years-old) Ph+ CP CML patients who were treated with IM for more than 3 years in sustained MR4.5 or undetectable transcript for at least 2 years are enrolled. MR4.5 or undetectable transcript must be sustained by 2 consecutive RQ-PCR assay within 6 months Exclusion Criteria: Patients were diagnosed with AP or BP CML Ph+ ALL Received cytotoxic chemotherapy or any other TKIs except imatinib Any evidence of on-going graft versus-host disease (GVHD) Relapsed patients after allogeneic stem cell transplantation

Ages Eligible for Study
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Minimum Age: 18 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Imatinib treatment discontinuing<br> | Behavioral: Imatinib treatment discontinuing<br>* Ph+ CP CML patients who were treated with IM for more than 3 years in sustained MR4.5 or undetectable transcript for at least 2 years are enrolled<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Probability of persistent undetectable molecular residual disease (UMRD) and MR4.5 | Our primary objectives were to evaluate the probability of persistent undetectable molecular residual disease (UMRD) and MR4.5 at 12 months after discontinuation, to measure the duration of persistent UMRD and MR4.5 after discontinuation, and to identify contributing factors for sustained undetectable transcript. | 12 months |