Clinical Trial: Therapies in Combination or Sequentially With Tyrosine Kinase Inhibitors (TKIs) in Chronic Phase Chronic Myelogenous Leukemia Patients in CCR (ACTIW)
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: Candidate Therapies in Combination or Sequentially With Tyrosine Kinase Inhibitors in Chronic Phase-chronic Myelogenous Leukemia Patients in CCR Without Achieving a Deep M
Brief Summary:
Patients will be randomized in phase II trials to continue on the same TKI versus one of the alternative treatment approaches. If a patient is not eligible for one of the treatments, he (she) will be randomized between the options for which he (she) is eligible.
The trial will start with current available treatment options (experimental arms). New available treatment options may be open at any times later on. Authorized TKIs are imatinib, nilotinib, dasatinib, bosutinib and ponatinib.
For all options the treatment duration is for a minimum of 12 months and will be continued in the absence of adverse events following investigator decision. Each therapeutic option will be detailed in term of combination modalities, dose, dose adaptation, specific warnings, specific exclusion and inclusion criteria. The decision to introduce a new option will depend on the general pace of recruitment and on the assessment of the potential efficacy and safety of the new treatment, and will be implemented after scientific review by a protocol amendment.
Primary objective:
A. To select molecules in combination or sequentially with imatinib, nilotinib, dasatinib, bosutinib or ponatinib potentially able to produce a 25% increase in the Cumulative Incidence of MR4.5 as compare to control.
Secondary objectives:
A. To determine the safety of selected therapies
B. To determine the rate of MR4 by 12, 24, 36, 48 months in experimental and control arms
C. To determine the rates of MR4.5 by 24, 36, 48 months in experimental and control arms
Patients will be randomised to continue on TKI (same daily dose) versus one of the X alternative novel treatment approaches. If a patient is not eligible for one of the treatments, he will be randomised between the options for which he is eligible.
All treatment options may be open at all times.
The first available treatment arms will be:
- TKI alone same daily dose (control arm)
- TKI in combination with pioglitazone
Planned treatment arms for the future may be :
- TKI in combination with pegylated interferon
- TKI in combination with arsenic trioxide
- TKI in combination with Homoharringtonine
- TKI in combination with anti-PD-L1 antibody
For all options the treatment plan is for at least 12 months depending on each molecule tested.
New treatment options will be introduced over time. The decision to introduce a new option will depend on the general pace of recruitment and the assessment of the potential efficacy and safety of the new treatment in this patient population, and will be implemented after scientific review by a protocol amendment.
Protocol plan:
-
Control arm (Imatinib, nilotinib, dasatinib, bosutinib or ponatinib):
Daily dose and schedule
Sponsor: Versailles Hospital
Current Primary Outcome: Cumulative incidence of patients achieving a deep molecular response [ Time Frame: 12 months ]
The cumulative incidence of patients achieving a deep molecular response defined by MR4.5 or deeper (BCR-ABLIS ≤ 0.0032 %) by 12 months
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Adverse events [ Time Frame: 12 Months ]Adverse events
- The cumulative rate of patients achieving MR4.5 by 24months in experimental and control arms [ Time Frame: 24 months ]The cumulative rate of patients achieving MR4.5 by 24months in experimental and control arms
- The cumulative rate of patients achieving MR4.5 by 36 months in experimental and control arms [ Time Frame: 36 months ]The cumulative rate of patients achieving MR4.5 by 36 months in experimental and control arms
- The cumulative rate of patients achieving MR4.5 by 48 months in experimental and control arms [ Time Frame: 48 months ]The cumulative rate of patients achieving MR4.5 by 48months in experimental and control arms
- The cumulative rate of patients achieving MR4 by 12months in experimental and control arms [ Time Frame: 12 months ]The cumulative rate of patients achieving MR4 by 12,months in experimental and control arms
- The cumulative rate of patients achieving MR4 by 24 months in experimental and control arms [ Time Frame: 24 months ]The cumulative rate of patients achieving MR4 by 24 months in experimental and control arms
- The cumulative rate of patients achieving MR4 by 36 months in experimental and control arms [ Time Frame: 36 months ]The cumulative rate of patients achieving MR4 by 36 months in experimental and control arms
- The cumulative rate of patients achieving MR4 by 48 months in experimental and control arms [ Time Frame: 48 months ]The cumulative rate of patients achieving MR4 by 48 months in experimental and control arms
- The cumulative rate of patients with undetectable BCR-ABL1 transcript (sensitivity 40000 ABL copies) by 12months in experimental and control arms [ Time Frame: 12 months ]The cumulative rate of patients with undetectable BCR-ABL1 transcript (sensitivity 40000 ABL copies) by 12months in experimental and control arms
- The cumulative rate of patients with undetectable BCR-ABL1 transcript (sensitivity 40000 ABL copies) by 24months in experimental and control arms [ Time Frame: 24 months ]The cumulative rate of patients with undetectable BCR-ABL1 transcript (sensitivity 40000 ABL copies) by 24, months in experimental and control arms
- The cumulative rate of patients with undetectable BCR-ABL1 transcript (sensitivity 40000 ABL copies) by 36 months in experimental and control arms [ Time Frame: 36 months ]The cumulative rate of patients with undetectable BCR-ABL1 transcript (sensitivity 40000 ABL copies) by 36 months in experimental and control arms
- The cumulative rate of patients with undetectable BCR-ABL1 transcript (sensitivity 40000 ABL copies) by 48 months in experimental and control arms [ Time Frame: 48 months ]The cumulative rate of patients with undetectable BCR-ABL1 transcript (sensitivity 40000 ABL copies) by 48 months in experimental and control arms
- The rate of patients in treatment free remission during follow-up [ Time Frame: 48 months ]The rate of patients in treatment free remission during follow-up
- Quantification of CML- and normal-CFU in bone marrow by clonogenic assays and RTQ- PCR [ Time Frame: 12 months ]
- Survival [ Time Frame: 48 months ]Survival
- duration of response [ Time Frame: 48 months ]duration of response
- event free survival [ Time Frame: 48 months ]event free survival
- progression free survival [ Time Frame: 48 months ]progression free survival
Original Secondary Outcome: Same as current
Information By: Versailles Hospital
Dates:
Date Received: March 16, 2016
Date Started: July 2016
Date Completion: June 2021
Last Updated: August 19, 2016
Last Verified: August 2016
- Adverse events [ Time Frame: 12 Months ]
