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

Sponsor

University of Campinas, Brazil (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02852486

Collaborator

(none)

Enrollment

Location

Arm

91.3

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia, Chronic Myeloid	Drug: Pioglitazone Other: imatinib discontinuation	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

31 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

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)

Actual Study Start Date :

Jun 22, 2016

Anticipated Primary Completion Date :

Feb 1, 2024

Anticipated Study Completion Date :

Feb 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pioglitazone Pioglitazone will be given 30 mg/day, orally, for 3 months, before imatinib discontinuation	Drug: Pioglitazone 30 mg/day, orally, for 3 months, before imatinib discontinuation Other: imatinib discontinuation imatinib discontinuation after 3 months of pioglitazone

Arm

Intervention/Treatment

Experimental: Pioglitazone

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

Drug: Pioglitazone

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

Other: imatinib discontinuation

imatinib discontinuation after 3 months of pioglitazone

Outcome Measures

Primary Outcome Measures

Treatment-free remission after imatinib discontinuation [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
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [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

Secondary Outcome Measures

proportion of patients with MMR, MR4.0, MR4.5 [3, 6 and 12 months]
Proportion of patients with MMR, MR4.0 and MR4.5 at 3, 6 and 12 months after imatinib discontinuation
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)]
Progression-free survival after imatinib discontinuation [Through study completion (five years)]
Event-free survival after imatinib discontinuation [Through study completion (five years)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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