Study of Imatinib Discontinuation in Chronic Myeloid Leukemia With Deep Molecular Response

NCT ID: NCT02852486

Last Updated: 2025-03-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-22
• Study Completion Date: 2024-02-07

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%.

Conditions

Leukemia, Chronic Myeloid

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Pioglitazone

Pioglitazone will be given 30 mg/day, orally, for 3 months, before imatinib discontinuation

Group Type: EXPERIMENTAL

Pioglitazone 30 Mg Oral Tablet

Intervention Type: DRUG

30 mg/day, orally, for 3 months, before imatinib discontinuation

imatinib discontinuation

Intervention Type: OTHER

imatinib discontinuation after 3 months of pioglitazone

Interventions

Pioglitazone 30 Mg Oral Tablet

30 mg/day, orally, for 3 months, before imatinib discontinuation

Intervention Type: DRUG

imatinib discontinuation

imatinib discontinuation after 3 months of pioglitazone

Intervention Type: OTHER

Other Intervention Names

cloridrato de pioglitazona 30mg EMS S/A, Brasil

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Campinas, Brazil

OTHER

Sponsor Role: lead

Responsible Party

Katia B. B. Pagnano

Hematologist, Hemocentro-Unicamp

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Katia B Pagnano, MD

Role: PRINCIPAL_INVESTIGATOR

University of Campinas

Locations

Centro de Hematologia e Hemoterapia - Universidade Estadual de Campinas

Campinas, São Paulo, Brazil

Countries

Brazil

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Other Identifiers

EDI-PIO-UNICAMP

Identifier Type: -

Identifier Source: org_study_id