Patient case: 52-year-old male with Lung cancer. Genetic variant: EML4-ALK Fusion transcript. Other conditions: Hypertension, Osteoarthritis.

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

Summary: 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: 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

Eligibility: 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

Relevance to patient case: not relevant