The purpose of this study is to evaluate treatment-free remission after imatinib discontinuation in patients with chronic myeloid leukemia with deep molecular response. Before discontinuation, patients will receive pioglitazone associated with imatinib during 3 months.
Treatment of chronic myeloid leucemia (CML) with tyrosine kinase inhibitors (TKIs) changed dramatically the prognosis of CML, with high rates of cytogenetic and molecular remission and increase of overall and progression-free survival. However, the long-term treatment of CML has a high cost to the health system, due to the price of these drugs and the need for continued use. In addition, chronic adverse effects may compromise the quality of life of patients. Discontinuation trials of TKIs have been developed in order to identify groups of patients who may benefit from treatment discontinuation if they have obtained deeper molecular responses.The primary objective of this study is to evaluate treatment free remission (TFR) after imatinib discontinuation in patients treated for more than 3 years with imatinib and with deep molecular response stable for two years (defined in the present study as a molecular response of 4.5 log reduction in breakpoint cluster region (BCR)-Abelson murine leukemia viral oncogene homolog 1(ABL) transcripts levels according to the international scale (MR 4.5; BCR-ABL/ABL ratio \< or = 0.0032%). Patients with these criteria will receive pioglitazone for 3 months concomitant with imatinib, prior to discontinuation. After imatinib discontinuation, patients will be evaluated by molecular assessment of BCR-ABL transcripts levels by quantitative real time polymerase chain reaction (RQ-PCR) monthly during the first year, every 2 months in the second year and then every 3 months. The criteria for restarting treatment will be the loss of major molecular response (MMR), documented by a single RQ-PCR test \> 0.1%, or confirmed loss of 4 log reduction molecular response (MR4.0), by 2 consecutive RQ-PCR tests \> 0.01%.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
31
30 mg/day, orally, for 3 months, before imatinib discontinuation
imatinib discontinuation after 3 months of pioglitazone
Centro de Hematologia e Hemoterapia - Universidade Estadual de Campinas
Campinas, São Paulo, Brazil
Treatment-free remission after imatinib discontinuation
Treatment-free remission time after imatinib discontinuation in patients with CML treated with pioglitazone for 3 months before imatinib discontinuation. Calculated from the date of imatinib discontinuation until imatinib reintroduction
Time frame: Through study completion (five years)
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
assessment of number of participants with treatment-related adverse events as assessed by CTCAE v4.0 during the 3 months of treatment with imatinib and pioglitazone
Time frame: 3 months
proportion of patients with MMR, MR4.0, MR4.5
Proportion of patients with MMR, MR4.0 and MR4.5 at 3, 6 and 12 months after imatinib discontinuation
Time frame: 3, 6 and 12 months
Time from imatinib discontinuation until loss of MMR
Time measured from the date of imatinib discontinuation until the date of loss of MMR, in days
Time frame: Through study completion (five years)
Rate of loss of complete cytogenetic response
% of patients who lost complete cytogenetic response
Time frame: Through study completion (five years)
Time to reach MMR after restarting imatinib
Time measured from the date of the reestart of imatinib until the achievement of MMR, days
Time frame: Through study completion (five years)
Overall survival after imatinib discontinuation
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Overall survival is calculated from the date of imatinib discontinuation until the date of death by any cause
Time frame: Through study completion (five years)
Progression-free survival after imatinib discontinuation
PFS is calculated from the date of imatinib discontinuatio until the date of progression of the disease
Time frame: Through study completion (five years)
Event-free survival after imatinib discontinuation
Event-free is calculated from the date of imatinib discontinuation until the date of loss of complete hematologic response, disease progression or death
Time frame: Through study completion (five years)
Molecular relapse free survival
Calculated from the date of imatinib discontinuation until de loss of major molecular response
Time frame: Through study completion (five years)