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

NCT02326311 | Completed Phase 3 DMC

• 1 other identifier: AOBSTMO-OPTKIMA-2014
• Study Type: interventional
• Target: 229
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

Fixed INTERIM TKI

ACTIVE COMPARATOR

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

Drug: imatinib; Drug: nilotinib; Drug: dasatinib

Progressive INTERIM TKI

EXPERIMENTAL

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; Drug: nilotinib; Drug: dasatinib

Interventions

imatinib DRUG

Tyrosin kinase inhibitor

Also known as: Glivec

Fixed INTERIM TKI; Progressive INTERIM TKI

nilotinib DRUG

Tyrosin kinase inhibitor

Also known as: Tasigna

Fixed INTERIM TKI; Progressive INTERIM TKI

dasatinib DRUG

Tyrosin kinase inhibitor

Also known as: Sprycell

Fixed INTERIM TKI; Progressive INTERIM TKI

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• \. 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).

Sponsors & Collaborators

• Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia: lead

Study Sites (1)

Policlinico Universitario di Milano

Milan, Italy

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Imatinib Mesylate; nilotinib; Dasatinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Thiazoles; Sulfur Compounds; Azoles

Study Officials

• Domenico Russo, Professor

  Chair of Hematology, BMT Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor of Hematology

Study Record Dates

• First Submitted: December 17, 2014
• First Posted: December 29, 2014
• Study Start: June 10, 2015
• Primary Completion: December 31, 2023
• Study Completion: May 29, 2024
• Last Updated: August 13, 2024

Record last verified: 2024-08

Locations

IT (1)