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

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

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.

Study Overview

• Status: Completed
• Conditions: Leukemia, Chronic Myeloid
• Intervention / Treatment: Drug: imatinib; Drug: nilotinib; Drug: dasatinib

• Study Type: Interventional
• Enrollment (Actual): 229
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Milano, Italy
    • Policlinico Universitario di Milano

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Fixed INTERIM TKI; Intervention: "fixed" intermittent administration (one month ON/one month OFF) of TKIs (imatinib, nilotinib, dasatinib)	Drug: imatinib; Tyrosin kinase inhibitor; Other Names: Glivec; Drug: nilotinib; Tyrosin kinase inhibitor; Other Names: Tasigna; Drug: dasatinib; Tyrosin kinase inhibitor; Other Names: Sprycell
Experimental: 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)	Drug: imatinib; Tyrosin kinase inhibitor; Other Names: Glivec; Drug: nilotinib; Tyrosin kinase inhibitor; Other Names: Tasigna; Drug: dasatinib; Tyrosin kinase inhibitor; Other Names: Sprycell

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
• Investigators: Principal Investigator: Domenico Russo, Professor, Chair of Hematology, BMT Unit

Study record dates

Study Major Dates

• Study Start (Actual): June 10, 2015
• Primary Completion (Actual): December 31, 2023
• Study Completion (Actual): May 29, 2024

Study Registration Dates

• First Submitted: December 17, 2014
• First Submitted That Met QC Criteria: December 22, 2014
• First Posted (Estimated): December 29, 2014

Study Record Updates

• Last Update Posted (Actual): August 13, 2024
• Last Update Submitted That Met QC Criteria: August 11, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Leukemia, Myeloid; Chronic Disease; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Tyrosine Kinase Inhibitors; Imatinib Mesylate; Dasatinib; Nilotinib
• Other Study ID Numbers: AOBSTMO-OPTKIMA-2014