Study of Imatinib Discontinuation in Chronic Myeloid Leukemia with Deep Molecular Response (EDI-PIO)

University of Campinas, Brazil

Status and phase

Completed

Phase 2

Conditions

Leukemia, Chronic Myeloid

Treatments

Other: imatinib discontinuation

Drug: Pioglitazone 30 Mg Oral Tablet

Study type

Interventional

Funder types

Other

Identifiers

NCT02852486

EDI-PIO-UNICAMP

Details and patient eligibility

About

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.

Full 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%.

Enrollment

31 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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