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

NCT02852486 | Completed Phase 2

• 1 other identifier: EDI-PIO-UNICAMP
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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.

Conditions

Leukemia, Chronic Myeloid

Keywords

BCR-ABL Positive; Leukemia, Chronic Myeloid; Imatinib; Pioglitazone

Outcome Measures

Primary Outcomes (2)

• 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

  Through study completion (five years)

• 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

  3 months

Secondary Outcomes (8)

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

  3, 6 and 12 months

• Time from imatinib discontinuation until loss of MMR

  Through study completion (five years)

• Rate of loss of complete cytogenetic response

  Through study completion (five years)

• Time to reach MMR after restarting imatinib

  Through study completion (five years)

• Overall survival after imatinib discontinuation

  Through study completion (five years)

Study Arms (1)

Pioglitazone

EXPERIMENTAL

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

Drug: Pioglitazone 30 Mg Oral Tablet; Other: imatinib discontinuation

Interventions

Pioglitazone 30 Mg Oral Tablet DRUG

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

Also known as: cloridrato de pioglitazona 30mg EMS S/A, Brasil

Pioglitazone

imatinib discontinuation OTHER

imatinib discontinuation after 3 months of pioglitazone

Pioglitazone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Campinas, Brazil: lead

Study Sites (1)

Centro de Hematologia e Hemoterapia - Universidade Estadual de Campinas

Campinas, São Paulo, 13083-868, Brazil

Location

Related Publications (15)

• 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.

  PMID: 21422402 BACKGROUND

• 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.

  PMID: 23620577 BACKGROUND

• 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.

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• 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.

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• 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.

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• 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.

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• 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.

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• 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.

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• 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.

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MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Pioglitazone; Tablets

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Katia B Pagnano, MD

  University of Campinas

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Hematologist, Hemocentro-Unicamp

Study Record Dates

• First Submitted: July 9, 2016
• First Posted: August 2, 2016
• Study Start: June 22, 2016
• Primary Completion: February 7, 2024
• Study Completion: February 7, 2024
• Last Updated: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will be available when summary data are published or otherwise made available
• Access Criteria: The requests will be reviewed by the principal investigator Katia Pagnano and contacts should be done by email (kborgia@unicamp.br)

Locations

BR (1)