Clinical trial NCT02852486: Study of Imatinib Discontinuation in Chronic Myeloid Leukemia With Deep Molecular Response
Official title: Pilot Study of Imatinib Discontinuation in Patients With Chronic Myeloid Leukemia With Deep Molecular Response - Evaluation of Pioglitazone in Treatment-free Remission (EDI-PIO)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia, Chronic Myeloid
Keywords: BCR-ABL Positive
Leukemia, Chronic Myeloid
Imatinib
Pioglitazone
Lead sponsor: University of Campinas, Brazil
Sponsor class: OTHER
First posted: 2016-08-02
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: 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.

Detailed description: 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%.

Eligibility criteria: Inclusion Criteria:

* CML in chronic phase
* treatment with imatinib for 3 or more years
* MR4.5 (RQ-PCR\< ou =0.0032%) confirmed by 4 RQ-PCR tests for BCR-ABL in the last 2 years (2 tests within the last 6 months)
* Eastern Cooperative Oncology Group Performance Status (ECOG) 0-2
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 reference level
* Bilirubins ≤ 1.5 reference level
* Contraceptive precautions for women

Exclusion Criteria:

* Patients less than 18 years
* Severe organ disfunction (liver or kidney)
* Severe cardiovascular disease: grade I-IV from New York Heart Association (NYHA) or acute myocardial infarction in the last six months, symptomatic arrhythmias
* Fluid retention grade 3 or 4
* Osteoporosis in treatment
* Patients with previous CML in accelerated or blast phase or blast or Philadelphia positive (Ph+) acute lymphoid leukemia (ALL)
* BCR-ABL mutations related to resistance
* Previous allogeneic bone marrow transplantation

Primary outcomes:
measure: Treatment-free remission after imatinib discontinuation
timeFrame: Through study completion (five years)
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: 3 months
Secondary outcomes:
measure: proportion of patients with MMR, MR4.0, MR4.5
timeFrame: 3, 6 and 12 months
measure: Time from imatinib discontinuation until loss of MMR
timeFrame: Through study completion (five years)
measure: Rate of loss of complete cytogenetic response
timeFrame: Through study completion (five years)
measure: Time to reach MMR after restarting imatinib
timeFrame: Through study completion (five years)
measure: Overall survival after imatinib discontinuation
timeFrame: Through study completion (five years)
measure: Progression-free survival after imatinib discontinuation
timeFrame: Through study completion (five years)
measure: Event-free survival after imatinib discontinuation
timeFrame: Through study completion (five years)
measure: Molecular relapse free survival
timeFrame: Through study completion (five years)
Other outcomes:
Locations:
city: Campinas
country: Brazil
facility: Centro de Hematologia e Hemoterapia - Universidade Estadual de Campinas
state: SP
Study officials:
affiliation: University of Campinas
name: Katia B Pagnano, MD
role: PRINCIPAL_INVESTIGATOR
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