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

November 28, 2023 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

Active, not recruiting

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

31

Phase

  • 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

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
Intervention / Treatment
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

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

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

University of Campinas, Brazil

Investigators

  • 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)

June 22, 2016

Primary Completion (Estimated)

February 1, 2024

Study Completion (Estimated)

February 1, 2024

Study Registration Dates

First Submitted

July 9, 2016

First Submitted That Met QC Criteria

July 28, 2016

First Posted (Estimated)

August 2, 2016

Study Record Updates

Last Update Posted (Estimated)

December 4, 2023

Last Update Submitted That Met QC Criteria

November 28, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID 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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