AzTrials
AzTrials

Leukemia, Chronic MyeloidPhase 2EDI-PIONCT02852486

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

A Phase 2 study testing Pioglitazone 30 Mg Oral Tablet and imatinib discontinuation in people with Leukemia, Chronic Myeloid, run by University of Campinas, Brazil at 1 site in Brazil.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Leukemia, Chronic Myeloid
What is being tested?
Pioglitazone 30 Mg Oral Tablet and imatinib discontinuation
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
1 siteBrazil
Study dates
22 Jun 2016to 7 Feb 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

Brazil1 site

  • Centro de Hematologia e Hemoterapia - Universidade Estadual de Campinas

    Campinas, São Paulo, 13083-868

Other trials in Brazil

About this study

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)

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.

Read the 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%.

Being tested
Pioglitazone 30 Mg Oral Tablet, imatinib discontinuation
Keywords
BCR-ABL Positive, Leukemia, Chronic Myeloid, Imatinib, Pioglitazone
Medical subject headings
Leukemia, Myelogenous, Chronic, BCR-ABL Positive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Pioglitazone 30 Mg Oral TabletDrug

    Also called cloridrato de pioglitazona 30mg EMS S/A, Brasil

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

  • imatinib discontinuationOther

    imatinib discontinuation after 3 months of pioglitazone

Study groups in NCT02852486
Study groupRoleWhat they receive
PioglitazoneExperimentalPioglitazone will be given 30 mg/day, orally, for 3 months, before imatinib discontinuation
Receives: Drug: Pioglitazone 30 Mg Oral Tablet; Other: imatinib discontinuation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Treatment-free remission after imatinib discontinuation

    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

    Measured: Through study completion (five years)

  2. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    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

    Measured: 3 months

Secondary outcomes (8)

  1. proportion of patients with MMR, MR4.0, MR4.5

    Proportion of patients with MMR, MR4.0 and MR4.5 at 3, 6 and 12 months after imatinib discontinuation

    Measured: 3, 6 and 12 months

  2. Time from imatinib discontinuation until loss of MMR

    Time measured from the date of imatinib discontinuation until the date of loss of MMR, in days

    Measured: Through study completion (five years)

  3. Rate of loss of complete cytogenetic response

    % of patients who lost complete cytogenetic response

    Measured: Through study completion (five years)

  4. Time to reach MMR after restarting imatinib

    Time measured from the date of the reestart of imatinib until the achievement of MMR, days

    Measured: Through study completion (five years)

  5. Overall survival after imatinib discontinuation

    Overall survival is calculated from the date of imatinib discontinuation until the date of death by any cause

    Measured: Through study completion (five years)

  6. Progression-free survival after imatinib discontinuation

    PFS is calculated from the date of imatinib discontinuatio until the date of progression of the disease

    Measured: Through study completion (five years)

  7. Event-free survival after imatinib discontinuation

    Event-free is calculated from the date of imatinib discontinuation until the date of loss of complete hematologic response, disease progression or death

    Measured: Through study completion (five years)

  8. Molecular relapse free survival

    Calculated from the date of imatinib discontinuation until de loss of major molecular response

    Measured: Through study completion (five years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Aug 2016 (estimated)
  2. Study start22 Jun 2016
  3. Primary completion7 Feb 2024
  4. Study completion7 Feb 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02852486
Sponsor's protocol ID
EDI-PIO-UNICAMP
Acronym
EDI-PIO
Status last verified
Mar 2025
First submitted
9 Jul 2016
Last updated
30 Mar 2025
Results posted
No
Data monitoring committee
No
Individual data sharing
Yes: 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)

Publications

  • Gambacorti-Passerini C, Antolini L, Mahon FX, Guilhot F, Deininger M, Fava C, Nagler A, Della Casa CM, Morra E, Abruzzese E, D'Emilio A, Stagno F, le Coutre P, Hurtado-Monroy R, Santini V, Martino B, Pane F, Piccin A, Giraldo P, Assouline S, Durosinmi MA, Leeksma O, Pogliani EM, Puttini M, Jang E, Reiffers J, Piazza R, Valsecchi MG, Kim DW. Multicenter independent assessment of outcomes in chronic myeloid leukemia patients treated with imatinib. J Natl Cancer Inst. 2011 Apr 6;103(7):553-61. doi: 10.1093/jnci/djr060. Epub 2011 Mar 21.

    PubMed 21422402

  • Experts in Chronic Myeloid Leukemia. The price of drugs for chronic myeloid leukemia (CML) is a reflection of the unsustainable prices of cancer drugs: from the perspective of a large group of CML experts. Blood. 2013 May 30;121(22):4439-42. doi: 10.1182/blood-2013-03-490003. Epub 2013 Apr 25.

    PubMed 23620577

  • Mahon FX, Rea D, Guilhot J, Guilhot F, Huguet F, Nicolini F, Legros L, Charbonnier A, Guerci A, Varet B, Etienne G, Reiffers J, Rousselot P; Intergroupe Francais des Leucemies Myeloides Chroniques. Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol. 2010 Nov;11(11):1029-35. doi: 10.1016/S1470-2045(10)70233-3. Epub 2010 Oct 19.

    PubMed 20965785

  • Rousselot P, Huguet F, Rea D, Legros L, Cayuela JM, Maarek O, Blanchet O, Marit G, Gluckman E, Reiffers J, Gardembas M, Mahon FX. Imatinib mesylate discontinuation in patients with chronic myelogenous leukemia in complete molecular remission for more than 2 years. Blood. 2007 Jan 1;109(1):58-60. doi: 10.1182/blood-2006-03-011239. Epub 2006 Sep 14.

    PubMed 16973963

  • Ross DM, Branford S, Seymour JF, Schwarer AP, Arthur C, Bartley PA, Slader C, Field C, Dang P, Filshie RJ, Mills AK, Grigg AP, Melo JV, Hughes TP. Patients with chronic myeloid leukemia who maintain a complete molecular response after stopping imatinib treatment have evidence of persistent leukemia by DNA PCR. Leukemia. 2010 Oct;24(10):1719-24. doi: 10.1038/leu.2010.185. Epub 2010 Sep 2.

    PubMed 20811403

  • Ross DM, Branford S, Seymour JF, Schwarer AP, Arthur C, Yeung DT, Dang P, Goyne JM, Slader C, Filshie RJ, Mills AK, Melo JV, White DL, Grigg AP, Hughes TP. Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: results from the TWISTER study. Blood. 2013 Jul 25;122(4):515-22. doi: 10.1182/blood-2013-02-483750. Epub 2013 May 23.

    PubMed 23704092

  • Takahashi N, Kyo T, Maeda Y, Sugihara T, Usuki K, Kawaguchi T, Usui N, Okamoto S, Ohe Y, Ohtake S, Kitamura K, Yamamoto M, Teshima H, Motoji T, Tamaki T, Sawada K, Ohyashiki K. Discontinuation of imatinib in Japanese patients with chronic myeloid leukemia. Haematologica. 2012 Jun;97(6):903-6. doi: 10.3324/haematol.2011.056853. Epub 2011 Dec 16.

    PubMed 22180435

  • Cross NC, White HE, Muller MC, Saglio G, Hochhaus A. Standardized definitions of molecular response in chronic myeloid leukemia. Leukemia. 2012 Oct;26(10):2172-5. doi: 10.1038/leu.2012.104. Epub 2012 Apr 16.

    PubMed 22504141

  • Rousselot P, Charbonnier A, Cony-Makhoul P, Agape P, Nicolini FE, Varet B, Gardembas M, Etienne G, Rea D, Roy L, Escoffre-Barbe M, Guerci-Bresler A, Tulliez M, Prost S, Spentchian M, Cayuela JM, Reiffers J, Chomel JC, Turhan A, Guilhot J, Guilhot F, Mahon FX. Loss of major molecular response as a trigger for restarting tyrosine kinase inhibitor therapy in patients with chronic-phase chronic myelogenous leukemia who have stopped imatinib after durable undetectable disease. J Clin Oncol. 2014 Feb 10;32(5):424-30. doi: 10.1200/JCO.2012.48.5797. Epub 2013 Dec 9.

    PubMed 24323036

  • Yhim HY, Lee NR, Song EK, Yim CY, Jeon SY, Shin S, Kim JA, Kim HS, Cho EH, Kwak JY. Imatinib mesylate discontinuation in patients with chronic myeloid leukemia who have received front-line imatinib mesylate therapy and achieved complete molecular response. Leuk Res. 2012 Jun;36(6):689-93. doi: 10.1016/j.leukres.2012.02.011. Epub 2012 Mar 5.

    PubMed 22398220

  • Branford S, Yeung DT, Ross DM, Prime JA, Field CR, Altamura HK, Yeoman AL, Georgievski J, Jamison BA, Phillis S, Sullivan B, Briggs NE, Hertzberg M, Seymour JF, Reynolds J, Hughes TP. Early molecular response and female sex strongly predict stable undetectable BCR-ABL1, the criteria for imatinib discontinuation in patients with CML. Blood. 2013 May 9;121(19):3818-24. doi: 10.1182/blood-2012-10-462291. Epub 2013 Mar 20.

    PubMed 23515925

  • Falchi L, Kantarjian HM, Wang X, Verma D, Quintas-Cardama A, O'Brien S, Jabbour EJ, Ravandi-Kashani F, Borthakur G, Garcia-Manero G, Verstovsek S, Burger JA, Luthra R, Cortes JE. Significance of deeper molecular responses in patients with chronic myeloid leukemia in early chronic phase treated with tyrosine kinase inhibitors. Am J Hematol. 2013 Dec;88(12):1024-9. doi: 10.1002/ajh.23560. Epub 2013 Sep 12.

    PubMed 23913852

  • Rea D, Rousselot P, Guilhot J, Guilhot F, Mahon FX. Curing chronic myeloid leukemia. Curr Hematol Malig Rep. 2012 Jun;7(2):103-8. doi: 10.1007/s11899-012-0117-2.

    PubMed 22410764

  • Prost S, Relouzat F, Spentchian M, Ouzegdouh Y, Saliba J, Massonnet G, Beressi JP, Verhoeyen E, Raggueneau V, Maneglier B, Castaigne S, Chomienne C, Chretien S, Rousselot P, Leboulch P. Erosion of the chronic myeloid leukaemia stem cell pool by PPARgamma agonists. Nature. 2015 Sep 17;525(7569):380-3. doi: 10.1038/nature15248. Epub 2015 Sep 2.

    PubMed 26331539

  • Wang T, Xu J, Yu X, Yang R, Han ZC. Peroxisome proliferator-activated receptor gamma in malignant diseases. Crit Rev Oncol Hematol. 2006 Apr;58(1):1-14. doi: 10.1016/j.critrevonc.2005.08.011. Epub 2006 Jan 18.

    PubMed 16388966

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pioglitazone 30 Mg Oral Tablet and imatinib discontinuation in people with Leukemia, Chronic Myeloid, run by University of Campinas, Brazil at 1 site in Brazil.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Treatment-free remission after imatinib discontinuation (time frame: Through study completion (five years)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02852486, which also lists 15 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in