Optimization of TKIs Treatment and Quality of Life in Ph+ CML Patients ≥60 Years in Deep Molecular Response

Study Overview
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Brief Summary
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In this phase III clinical randomized study, fixed intermittent administration (one month ON/one month OFF) of TKIs (control arm), will be compared with progressive intermittent administration (one month ON/one month OFF for the 1st year; one month ON/two months OFF for the 2nd year; one month ON/three months OFF for the 3rd year) (experimental arm). Imatinib (Glivec), or Nilotinib (Tasigna), or Dasatinib (Sprycel) will be given intermittently at the same daily dose that was given daily at the time of the enrollment . Chronic phase Ph+ CML patients in stable major molecular response (MR3.0 or MR4.0) after ≥2 years of standard treatment with IM, NIL, or DAS will be randomized 1:1 to receive fixed INTERIM or progressive INTERIM. Randomization will be stratified by type of TKI (IM, NIL, or DAS,) and by depth of molecular response (MR3.0or MR4.0). The study is aimed to evaluate if a progressive increase of intermittent treatment discontinuation until 3 months is able to improve QoL outcomes with respect to fixed intermittent administration of TKIs (control arm) and to maintain MR3.0 / MR4.0 molecular response. Patients' self reported EORTC QLQ-C30 outcome measure will be assessed throughout the three years follow up period. The QoL results in this trial will be presented in accordance with high methodological quality criteria for documenting patient-reported outcomes (PRO) data in RCTs, including the CONSORT PRO recommendations. Furthermore, the study could give additional clinical and biological information to optimize TKIs therapy in elderly.

Official Title
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Phase-III Randomized Study to Optimize TKIs Multiple Approaches - (OPTkIMA) - and Quality of Life (QoL) in Elderly Patients (≥60 Years) With Ph+ Chronic Myeloid Leukemia (CML) and MR3.0 / MR4.0 Stable Molecular Response

Conditions
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Leukemia, Chronic Myeloid

Intervention / Treatment
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* Drug: imatinib
* Drug: nilotinib
* Drug: dasatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a confirmed diagnosis of Ph+ CML in CP Age ≥ 60 years old Stable MR3.0/ MR4.0 after at least 2 years of treatment with standard (daily administration) IM, NIL, or DAS therapy; the stability of molecular response will be documented by at least 3 consecutive molecular analyses over the last 12 months. Having completed the QoL baseline evaluation (i.e., before randomization) Written informed consent prior to any study procedures Exclusion Criteria: Patients with Ph+ CML in accelerated/blastic phase (AP/BP), or in late CP previously treated (i.e. IFNalpha+/- low dose Ara-C, Hydroxurea, allogeneic stem cell transplantation, etc) Age < 60 years old Less than 2 years of treatment with standard (continuous administration) IM, NIL or DAS therapy 3. Absence of stable MR3.0/MR4.0 as documented by at least 3 consecutive molecular analyses over the last 12 months 4. No written informed consent prior to any study procedures. 5. Having any kind of psychiatric disorder or major cognitive dysfunction hampering a QoL evaluation (as judged by the physician).

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Fixed INTERIM TKI<br>Intervention: fixed intermittent administration (one month ON/one month OFF) of TKIs (imatinib, nilotinib, dasatinib) | Drug: imatinib<br>* Tyrosin kinase inhibitor<br>* Other names: Glivec;Drug: nilotinib<br>* Tyrosin kinase inhibitor<br>* Other names: Tasigna;Drug: dasatinib<br>* Tyrosin kinase inhibitor<br>* Other names: Sprycell;|
| Experimental: Progressive INTERIM TKI<br>Intervention: progressive intermittent administration (one month ON/one month OFF for the 1st year; one month ON/two months OFF for the 2nd year; one month ON/three months OFF for the 3rd year) (imatinib, nilotinib, dasatinib) | Drug: imatinib<br>* Tyrosin kinase inhibitor<br>* Other names: Glivec;Drug: nilotinib<br>* Tyrosin kinase inhibitor<br>* Other names: Tasigna;Drug: dasatinib<br>* Tyrosin kinase inhibitor<br>* Other names: Sprycell;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in quality of Life |  | Baseline (T0), and then at 3 (T1), 6 (T2), 9 (T3), 12 (T4), 18 (T5), 24 (T6), 30 (T7), and 36 (T8) months |