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
18 Years
N/A
Both
Chronic Myeloid Leukemia, Imatinib, Complete Molecular Response
Trial Information
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
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
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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Probability of persistent undetectable molecular residual disease (UMRD) and MR4.5
Outcome Description:
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.
Outcome Time Frame:
12 months
Safety Issue:
No
Authority:
Korea: Food and Drug Administration
Study ID:
KC10ENME0465
NCT ID:
NCT01564836
Start Date:
June 2010
Completion Date:
Related Keywords:
- Chronic Myeloid Leukemia
- Imatinib
- Complete Molecular Response
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
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