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

Phase 3

Completed

• Conditions: Leukemia, Chronic Myeloid
• Interventions: Drug: imatinib; Drug: nilotinib; Drug: dasatinib

• Registration Number: NCT02326311
• Lead Sponsor: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-12-17
• Study First Submitted QC: 2014-12-22
• Study First Posted: 2014-12-29
• Study Start: 2015-06-10
• Primary Completion: 2023-12-31
• Study Completion: 2024-05-29
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-11
• Last Update Posted: 2024-08-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 229

Inclusion Criteria

1. Patients with a confirmed diagnosis of Ph+ CML in CP
2. Age ≥ 60 years old
3. 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.
4. Having completed the QoL baseline evaluation (i.e., before randomization)
5. Written informed consent prior to any study procedures

Exclusion Criteria

1. 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)

2. Age < 60 years old

3. Less than 2 years of treatment with standard (continuous administration) IM, NIL or DAS therapy

4. 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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fixed INTERIM TKI	dasatinib	Intervention: "fixed" intermittent administration (one month ON/one month OFF) of TKIs (imatinib, nilotinib, dasatinib)
Fixed INTERIM TKI	imatinib	Intervention: "fixed" intermittent administration (one month ON/one month OFF) of TKIs (imatinib, nilotinib, dasatinib)
Fixed INTERIM TKI	nilotinib	Intervention: "fixed" intermittent administration (one month ON/one month OFF) of TKIs (imatinib, nilotinib, dasatinib)
Progressive INTERIM TKI	imatinib	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)
Progressive INTERIM TKI	nilotinib	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)
Progressive INTERIM TKI	dasatinib	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)

Primary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Policlinico Universitario di Milano; 🇮🇹 Milano, Italy