CML
Conditions
Keywords
DISCONTINUATION
Brief summary
The principal aim of this study is to evaluate complete molecular remission in patients with chronic myeloid leukemia (CML) in deep molecular response after stopping tyrosine kinase inhibitor (TKI) treatment. The second aim is to characterize the immunological status of patients with CML at the time of TKI interruption and then at 3 months after the interruption.
Detailed description
ARGENTINA STOP TRIAL is a multicentre, open-label, uncontrolled trial to estimate the persistence of molecular remission in patients with chronic phase Chronic Myeloid Leukemia (CML) in Deep Molecular Response after stopping Tyrosine Kinase Inhibitor (TKI) Primary Objective: \- To identify the proportion of patients who continue on Major Molecular Response after discontinuing treatment with TKI. Secondary objectives: * To characterize the immunological status of patients with CML at the time of interruption and then at 3 and 12 months after the interruption. Tertiary objective: To evaluate the pharmacoeconomic impact of interrupting the treatment.
Interventions
DRUGDiscontinuing treatment with Tyrosine Kinase Inhibitor after enrolment
Discontinuing treatment with Tyrosine Kinase Inhibitor after enrolment with a scheduled molecular monitoring until month 24.
Sponsors
Fundaleu
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
multicentre, open-label, uncontrolled trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
1. Signed Informed consent. 2. Patients with a diagnosis of CML BCR-ABL positive in CP treated with approved TKI (Imatinib, Nilotinib or Dasatinib) in 1st line or in 2nd line due to intolerance to the 1st line or in 2nd line due to the lack of deep MR with 1st line TKI, which never presented criteria for treatment failure. 3. Age ≥ 18 years 4. ≥ 4 years of treatment with imatinib, nilotinib or dasatinib. 5. Achievement of MR 4.5 in a standardized laboratory (BCR-ABL1 IS ≤ 0.0032%). 6. Evidence of MR 4.5 sustained for ≥ 2 years, as documented in at least 4 tests performed at least 3 months apart. 7. Evidence of typical quantifiable BCR-ABL1 transcript (b3a2 \[e14a2\] and / or b2a2 \[e13a2\], typical isoforms of p210).
Exclusion criteria
1. Patients who previously discontinued TKI and demonstrated recurrence of the disease. 2. Patients with failure to any TKI at any time. 3. Patients who presented accelerated phase or CML in blast crisis at any time. 4. Patients with atypical transcript not quantifiable by RT qPCR 5. BCR-ABL mutation detected at any time during the course of the resistant disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Molecular relapse free survival during 24 months | 24 months | Molecular relapse free survival, defined as the time from the start of TKI interruption until the loss of the MMR. RQ PCR (IS) \>0.1% BCR ABL will be considered as loss of MMR |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-free survival during 24 months | 24 months | Treatment-free survival , defined as the time from the start of TKI interruption to the restart of the TKI. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Overall survival during 24 months | 24 months | Overall survival, defined from the day of TKI interruption until date of death, date of last contact or loss of follow-up. |
| Pharmacoeconomic analysis during 24 months | 24 months | Calculate the total saving of the included patients un US dollars, considering the costs of TKIs, PCRs performing and medical visits, |
Countries
Argentina
Contacts
Primary ContactCarolina Pavlovsky, MD
Backup ContactMariana Juni
Outcome results
None listed