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

NCT ID: NCT02326311

Last Updated: 2024-08-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 229 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-10
• Study Completion Date: 2024-05-29

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.

Conditions

Leukemia, Chronic Myeloid

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Fixed INTERIM TKI

Intervention: "fixed" intermittent administration (one month ON/one month OFF) of TKIs (imatinib, nilotinib, dasatinib)

Group Type: ACTIVE_COMPARATOR

imatinib

Intervention Type: DRUG

Tyrosin kinase inhibitor

nilotinib

Intervention Type: DRUG

Tyrosin kinase inhibitor

dasatinib

Intervention Type: DRUG

Tyrosin kinase inhibitor

Progressive INTERIM TKI

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)

Group Type: EXPERIMENTAL

imatinib

Intervention Type: DRUG

Tyrosin kinase inhibitor

nilotinib

Intervention Type: DRUG

Tyrosin kinase inhibitor

dasatinib

Intervention Type: DRUG

Tyrosin kinase inhibitor

Interventions

imatinib

Tyrosin kinase inhibitor

Intervention Type: DRUG

nilotinib

Tyrosin kinase inhibitor

Intervention Type: DRUG

dasatinib

Tyrosin kinase inhibitor

Intervention Type: DRUG

Other Intervention Names

Glivec; Tasigna; Sprycell

Eligibility Criteria

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

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).

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

OTHER

Sponsor Role: lead

Responsible Party

Prof Domenico Russo

Full Professor of Hematology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Domenico Russo, Professor

Role: PRINCIPAL_INVESTIGATOR

Chair of Hematology, BMT Unit

Locations

Policlinico Universitario di Milano

Milan, , Italy

Countries

Italy

Other Identifiers

AOBSTMO-OPTKIMA-2014

Identifier Type: -

Identifier Source: org_study_id