Treatment Free RemissionNCT04769947
Italian Treatment Free Remission Registry
An observational study of Treatment Free Remission and Chronic Myeloid Leukemia, run by University of Turin, Italy at 1 site in Italy.
Trial summary
The investigator propose an extension of the previous National, multicentric study, promoting an observational registry, both retrospective and prospective, in order to expand and further characterize the series of Italian patients with Philadelphia-positive, chronic phase CML (CP-CML) who discontinue TKIs in an… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Treatment Free Remission, Chronic Myeloid Leukemia
- How many people
- 800 participants
- Where
- 1 siteItaly
- Study dates
- 9 Aug 2021to 8 Feb 2030
- How long will I take part?
- 5 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients with CP-CML who discontinued treatment with TKIs in Italy will be selected.
Who may be able to join
- Patients with CP-CML, treated with TKI monotherapy or TKI in association with other drugs (such as interferon, BCR-ABL1 peptidic vaccine and others)
- Treatment with TKI discontinued for any reason
- Deep Molecular Response (DMR), defined as MR4 (BCR-ABL1 ratio ≤ 0.01% with at least 10,000 ABL1 copies), or MR4.5 (BCR-ABL1 ratio ≤ 0.0032% with at least 32,000 ABL1 copies), or MR5 (BCR-ABL1 ratio ≤ 0.001% with at least 100,000 ABL1 copies), confirmed at least three times before TKI discontinuation. In patients who discontinued TKIs before the establishment of molecular standardization, DMR will be defined as a level of BCR-ABL1 transcript undetectable by qPCR or by qualitative PCR, confirmed in at least two controls.
- Participant is willing and able to give informed consent for participation in the study Data regarding patients discontinuing in less than DMR (as defined above) will be collected and analysed separately.
Who cannot join
- Patients who were diagnosed with accelerated or blastic phase CML will be excluded
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Division of Hematology-AO Mauriziano Hospital, University of Turin
Turin, 10128
Carmen Fava, MD, PhD
About this study
Official title: Observational Study in Adult Patient With Chronic Myeloid Leukemia Who Discontinue Tyrosine Kinase Inhibitors in Italy
The investigator propose an extension of the previous National, multicentric study, promoting an observational registry, both retrospective and prospective, in order to expand and further characterize the series of Italian patients with Philadelphia-positive, chronic phase CML (CP-CML) who discontinue TKIs in an off-protocol setting. As safety concerns may arise for patients receiving long-term treatments, and due to the growing number of patients discontinuing TKIs in clinical practice, the study aim to collect all available data regarding feasibility and freedom from progression of the cohort of patients.
Read the detailed description
This is an observational, retrospective and prospective study of CP-CML patients who discontinue TKIs in Italy. The study will not imply additional costs for the participating centers. Data already present in the clinical charts will be collected.
The patients, answering to inclusion/exclusion criteria will be enrolled in one of the follow cohorts
- Cohort 1 retrospective/prospective study: 293 patients enrolled and reported in Fava et al 2019 with at least 1 year of follow up at the end of the study (February 2017) and 107 patients enrolled but not reported in Fava et al 2019 since their follow-up was shorter than 1 year. The data for these patients will be collected since the end of previous study.
- Cohort 2 retrospective/prospective study: patient not enrolled in the previous study (Fava et al 2019). The data for these patients will be collected since patient diagnosis to the end of the study.
- Cohort 3 prospective study: patients who have discontinued TKI therapy after the study approval in each center. These patients will also participate in the validation process of Phase 2 of a questionnaire developed by an expert panel of eight CML patients with the purpose of capturing the experiences of people along all phases of the TFR.
Patients participating in the study will not be subjected to any procedure that falls outside the clinical practice; in the same way, clinical variables that will be collected for the study are those that are commonly collected by physician in daily clinical practice.
Any decision about drug administration or suspension is made by the physician based on his clinical judgment in the context of clinical practice, independently from decision to include the patient in this study.
Registration of enrolled patients will be done on-line on a key restricted accessible web-database.
Primary objective and endpoint To assess the TFR rate at 1 year from discontinuation of TKIs. Secondary objectives and endpoints
- To further describe the observed population of patients in terms of:
- treatment-free duration; o survival in MR4.5;
- survival in MR3;
- event-free survival;
- progression-free survival;
- deaths after treatment discontinuation;
- rate of achievement of MMR and DMR after treatment re-initiation
- To identify clinical and biological prognostic factors affecting the persistence of off-therapy remission.
- To identify optimal timing and modalities of molecular monitoring of BCR-ABL1 transcript
- Evaluation of the safe minimum monitoring during and after treatment discontinuation
- Evaluation of the maximum MRD positivity level acceptable to safely stay off-treatment
- Evaluation of short-term adverse events (withdrawal syndrome: fever, arthralgia, myalgia, bone pain, weight loss) after treatment discontinuation
- Evaluation of long-term adverse events (i.e. cardiovascular adverse events, second neoplasia) after treatment discontinuation
- Validation of the Italian version of the "Phase 2" of a questionnaire developed by an expert panel of eight CML patients to capture the experiences of people along all phases of the TFR
- Evaluation of patient-reported outcomes describing quality of life of patients off therapy and after resumption of TKIs
- Conditions
- Treatment Free Remission, Chronic Myeloid Leukemia
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Cohort 1 retrospective/prospective study: 293 patients enrolled and reported in Fava et al 2019 (1) with at least 1 year of follow up at the end of the study (February 2017) and 107 patients enrolled but not reported in Fava et al 2019 since their follow-up was shorter than 1 year. The data for these patients will be collected since the end of previous study. | |
| Cohort 2 | Cohort 2 retrospective/prospective study: patient not enrolled in the previous study (Fava et al 2019). The data for these patients will be collected since patient diagnosis to the end of the study. | |
| Cohort 3 | Cohort 3 prospective study: patients who have discontinued TKI therapy after the study approval in each center. These patients will also participate in the validation process of Phase 2 of a questionnaire developed by an expert panel of eight CML patients with the purpose of capturing the experiences of people along all phases of the TFR. |
What is being measured
The primary outcome is the main question the study is designed to answer.
TFR rate at 1 year from discontinuation of TKIs
To assess the TFR rate at 1 year from discontinuation of TKIs
Measured: 1 year
Secondary outcomes (1)
Secondary objectives
treatment-free duration (months); survival in MR4.5 (%); survival in MR3 (%); event-free survival (%); progression-free survival (%); deaths after treatment discontinuation (%); rate of achievement of MMR and DMR after treatment re-initiation (%)
Measured: 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2021
- Study start9 Aug 2021
- Primary completion8 Jul 2022 (estimated)
- Study completion8 Feb 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Treatment Free RemissionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 800 participants (estimated)
- Target duration
- 5 Years
Sponsor and investigators
- Lead sponsor
- University of Turin, Italy
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04769947
- Sponsor's protocol ID
- ITALY-TFR
- Status last verified
- May 2021
- First submitted
- 10 Feb 2021
- Last updated
- 18 Nov 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Observational Study in Adult Patient With Chronic Myeloid Leukemia Who Discontinue Tyrosine Kinase Inhibitors in Italy
- ClinicalTrials.gov ID
- NCT04769947
- Acronym / sponsor ID
- ITALY-TFR
- Conditions
- Treatment Free Remission, Chronic Myeloid Leukemia
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 800 participants (estimated)
- Lead sponsor
- University of Turin, ItalyUniversity, hospital or other
- Study start
- 9 Aug 2021 (actual)
- Primary completion
- 8 Jul 2022 (estimated)
- Study completion
- 8 Feb 2030 (estimated)
- First posted
- 25 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigator propose an extension of the previous National, multicentric study, promoting an observational registry, both retrospective and prospective, in order to expand and further characterize the series of Italian patients with Philadelphia-positive, chronic phase CML (CP-CML) who discontinue TKIs in an off-protocol setting. As safety concerns may arise for patients receiving long-term treatments, and due to the growing number of patients discontinuing TKIs in clinical practice, the study aim to collect all available data regarding feasibility and freedom from progression of the cohort of patients.
Detailed description
This is an observational, retrospective and prospective study of CP-CML patients who discontinue TKIs in Italy. The study will not imply additional costs for the participating centers. Data already present in the clinical charts will be collected.
The patients, answering to inclusion/exclusion criteria will be enrolled in one of the follow cohorts
- Cohort 1 retrospective/prospective study: 293 patients enrolled and reported in Fava et al 2019 with at least 1 year of follow up at the end of the study (February 2017) and 107 patients enrolled but not reported in Fava et al 2019 since their follow-up was shorter than 1 year. The data for these patients will be collected since the end of previous study.
- Cohort 2 retrospective/prospective study: patient not enrolled in the previous study (Fava et al 2019). The data for these patients will be collected since patient diagnosis to the end of the study.
- Cohort 3 prospective study: patients who have discontinued TKI therapy after the study approval in each center. These patients will also participate in the validation process of Phase 2 of a questionnaire developed by an expert panel of eight CML patients with the purpose of capturing the experiences of people along all phases of the TFR.
Patients participating in the study will not be subjected to any procedure that falls outside the clinical practice; in the same way, clinical variables that will be collected for the study are those that are commonly collected by physician in daily clinical practice.
Any decision about drug administration or suspension is made by the physician based on his clinical judgment in the context of clinical practice, independently from decision to include the patient in this study.
Registration of enrolled patients will be done on-line on a key restricted accessible web-database.
Primary objective and endpoint To assess the TFR rate at 1 year from discontinuation of TKIs. Secondary objectives and endpoints
- To further describe the observed population of patients in terms of:
- treatment-free duration; o survival in MR4.5;
- survival in MR3;
- event-free survival;
- progression-free survival;
- deaths after treatment discontinuation;
- rate of achievement of MMR and DMR after treatment re-initiation
- To identify clinical and biological prognostic factors affecting the persistence of off-therapy remission.
- To identify optimal timing and modalities of molecular monitoring of BCR-ABL1 transcript
- Evaluation of the safe minimum monitoring during and after treatment discontinuation
- Evaluation of the maximum MRD positivity level acceptable to safely stay off-treatment
- Evaluation of short-term adverse events (withdrawal syndrome: fever, arthralgia, myalgia, bone pain, weight loss) after treatment discontinuation
- Evaluation of long-term adverse events (i.e. cardiovascular adverse events, second neoplasia) after treatment discontinuation
- Validation of the Italian version of the "Phase 2" of a questionnaire developed by an expert panel of eight CML patients to capture the experiences of people along all phases of the TFR
- Evaluation of patient-reported outcomes describing quality of life of patients off therapy and after resumption of TKIs
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 5 Years
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | – | –Cohort 1 retrospective/prospective study: 293 patients enrolled and reported in Fava et al 2019 (1) with at least 1 year of follow up at the end of the study (February 2017) and 107 patients enrolled but not reported in Fava et al 2019 since their follow-up was shorter than 1 year. The data for these patients will be collected since the end of previous study. |
| Cohort 2 | – | –Cohort 2 retrospective/prospective study: patient not enrolled in the previous study (Fava et al 2019). The data for these patients will be collected since patient diagnosis to the end of the study. |
| Cohort 3 | – | –Cohort 3 prospective study: patients who have discontinued TKI therapy after the study approval in each center. These patients will also participate in the validation process of Phase 2 of a questionnaire developed by an expert panel of eight CML patients with the purpose of capturing the experiences of people along all phases of the TFR. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with CP-CML who discontinued treatment with TKIs in Italy will be selected.
Key inclusion criteria (4 listed)
- Patients with CP-CML, treated with TKI monotherapy or TKI in association with other drugs (such as interferon, BCR-ABL1 peptidic vaccine and others)
- Treatment with TKI discontinued for any reason
- Deep Molecular Response (DMR), defined as MR4 (BCR-ABL1 ratio ≤ 0.01% with at least 10,000 ABL1 copies), or MR4.5 (BCR-ABL1 ratio ≤ 0.0032% with at least 32,000 ABL1 copies), or MR5 (BCR-ABL1 ratio ≤ 0.001% with at least 100,000 ABL1 copies), confirmed at least three times before TKI discontinuation. In patients who discontinued TKIs before the establishment of molecular standardization, DMR will be defined as a level of BCR-ABL1 transcript undetectable by qPCR or by qualitative PCR, confirmed in at least two controls.
- Participant is willing and able to give informed consent for participation in the study Data regarding patients discontinuing in less than DMR (as defined above) will be collected and analysed separately.
Key exclusion criteria (1 listed)
- Patients who were diagnosed with accelerated or blastic phase CML will be excluded
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
TFR rate at 1 year from discontinuation of TKIs
Time frame: 1 year
To assess the TFR rate at 1 year from discontinuation of TKIs
1 secondary outcome
Secondary objectives
Time frame: 10 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Treatment Free Remission and Chronic Myeloid Leukemia, run by University of Turin, Italy at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Carmen Fava, MD, PhD (0115085523 ext. +39, carmen.fava@unito.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
TFR rate at 1 year from discontinuation of TKIs (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2021.