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

Leukemia, Chronic Myeloid Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02326311
• Other study ID #: AOBSTMO-OPTKIMA-2014
• Status: Recruiting
• Phase: Phase 3
• Start date: June 10, 2015
• Est. completion date: December 31, 2023

Study information

• Verified date: July 2023
• Source: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
• Contact: Domenico Russo, Professor
• Phone: +390303996810
• Email: domenico.russo[@]unibs.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 502
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Chronic Myeloid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Intervention

Drug:
• imatinib
Tyrosin kinase inhibitor
• nilotinib
Tyrosin kinase inhibitor
• dasatinib
Tyrosin kinase inhibitor

Locations

Country	Name	City	State
Italy	Policlinico Universitario di Milano	Milano

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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