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

March 25, 2025 updated by: Katia B. B. Pagnano, University of Campinas, Brazil

Pilot Study of Imatinib Discontinuation in Patients with Chronic Myeloid Leukemia with Deep Molecular Response - Evaluation of Pioglitazone in Treatment-free Remission (EDI-PIO)

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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%.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
31

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
    • SP
      • Campinas, SP, Brazil, 13083-868
        • Centro de Hematologia e Hemoterapia - Universidade Estadual de Campinas

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Pioglitazone
Pioglitazone will be given 30 mg/day, orally, for 3 months, before imatinib discontinuation
Other: imatinib discontinuation
imatinib discontinuation after 3 months of pioglitazone
Drug: Pioglitazone 30 Mg Oral Tablet
30 mg/day, orally, for 3 months, before imatinib discontinuation
Other Names:
  • cloridrato de pioglitazona 30mg EMS S/A, Brasil

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame: 3 months
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
3 months
Treatment-free remission after imatinib discontinuation
Time Frame: Through study completion (five years)
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
Through study completion (five years)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
proportion of patients with MMR, MR4.0, MR4.5
Time Frame: 3, 6 and 12 months
Proportion of patients with MMR, MR4.0 and MR4.5 at 3, 6 and 12 months after imatinib discontinuation
3, 6 and 12 months
Time from imatinib discontinuation until loss of MMR
Time Frame: Through study completion (five years)
Time measured from the date of imatinib discontinuation until the date of loss of MMR, in days
Through study completion (five years)
Rate of loss of complete cytogenetic response
Time Frame: Through study completion (five years)
% of patients who lost complete cytogenetic response
Through study completion (five years)
Time to reach MMR after restarting imatinib
Time Frame: Through study completion (five years)
Time measured from the date of the reestart of imatinib until the achievement of MMR, days
Through study completion (five years)
Overall survival after imatinib discontinuation
Time Frame: Through study completion (five years)
Overall survival is calculated from the date of imatinib discontinuation until the date of death by any cause
Through study completion (five years)
Progression-free survival after imatinib discontinuation
Time Frame: Through study completion (five years)
PFS is calculated from the date of imatinib discontinuatio until the date of progression of the disease
Through study completion (five years)
Event-free survival after imatinib discontinuation
Time Frame: Through study completion (five years)
Event-free is calculated from the date of imatinib discontinuation until the date of loss of complete hematologic response, disease progression or death
Through study completion (five years)
Molecular relapse free survival
Time Frame: Through study completion (five years)
Calculated from the date of imatinib discontinuation until de loss of major molecular response
Through study completion (five years)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Campinas, Brazil

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Katia B Pagnano, MD, University of Campinas

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 22, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 7, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 7, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 9, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 28, 2016

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 2, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 30, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 25, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • EDI-PIO-UNICAMP

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data will be available for other researchers upon reasonable request with the principal investigator (Katia Pagnano) (all collected IPD, all IPD that underlie results in a publication)

IPD Sharing Time Frame

Data will be available when summary data are published or otherwise made available

IPD Sharing Access Criteria

The requests will be reviewed by the principal investigator Katia Pagnano and contacts should be done by email (kborgia@unicamp.br)

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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