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Chronic Myeloid LeukemiaNCT04621851

Retro-prospective Observational Study on Risk of Progression in CP-CML Patients Eligible for TKI Discontinuation

An observational study of Chronic Myeloid Leukemia, run by University of Milano Bicocca at 26 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to investigate the safety profile of TKI discontinuation in clinical practice, with particular regard on the risk of progression after treatment discontinuation. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chronic Myeloid Leukemia
How many people
260 participants
Where
26 sitesin 4 countries
Study dates
30 Sep 2020to 14 Aug 2023
How long will I take part?
36 Months
Phase
Observational
Are there results?
None posted in the registry

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
  • No healthy volunteers
  • Adult, Older adult

Study population: The target population will include all CML patients presently eligible for treatment discontinuation independently of whether they discontinued or not. For the time they did not discontinue they will contribute to the reference cohort, while after TD they will contribute data to the discontinuation cohort. In case of treatment resumption, the patient will still contribute to the discontinuation cohort for 36 months after treatment resumption, while he/she will contribute to the reference cohort thereafter, assuming a new TD did not occur.

Who may be able to join

  • Signed and dated IRB/IEC-approved informed consent for the prospective cohort patients.
  • Age >= 18 years.
  • Male or female patients with CML diagnosed in chronic phase (CP).
  • At least 4 years of TKI treatment.
  • At least 18 months of DMR.

Who cannot join

  • Allogeneic hematopoietic stem cell transplantation.
  • CML diagnosed in AP or BC

Trial locations and contacts

26 sites in 4 countries.

26 sites in 4 countries

Italy22 sites

  • Istituto di Ematologia "Lorenzo e A. Seragnoli" Policlinico S. Orsola Malpighi,

    Bologna

  • CTMO Ematologia Ospedale "Businco"

    Cagliari

  • Università di Catania Cattedra di Ematologia Ospedale "Ferrarotto"

    Catania

  • SOC Ematologia Az. Ospedaliera Pugliese Ciaccio (AOPC)

    Catanzaro

  • Ematologia Ospedale Cuneo

    Cuneo

  • UO Ematologia O spedale Milano S. Raffaele

    Miano

  • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico UOC di Ematologia

    Milan, Italy/Milano, 20162

  • ASST-Monza

    Monza, Italy/MB, 20900

  • Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli"

    Naples

  • Azienda Ospedaliera Universitaria Università degli Studi di Napoli "Federico II" Facoltà di Medicina e Chirurgia

    Naples

  • U.O. di Ematologia con trapianto A.U. Policlinico "Paolo Giaccone"

    Palermo

  • Unità operativa Ematologia e CTMO Az Ospedaliera Universitaria

    Parma

  • Fondazione IRCCS Policlinico San Matteo

    Pavia

  • Università di Pisa Azienda Ospedaliera Pisana Divisione di Ematologia

    Pisa

  • Azienda Unità Sanitaria Locale IRCCS

    Reggio Emilia

  • Universita di Tor Vergata Ospedale S. Eugenio

    Rome, Italy/Rome, 00142

  • Dipartimento di Oncologia ed Ematologia S.C. Ematologia 2 A.O. Città della Salute e della Scienza di Torino S. G.Battista

    Torino

  • Struttura Complessa a Dir. Universitaria Ematologia e Terapie Cellulari A.S.O. Ordine Mauriziano, P.O. U mberto I

    Torino

  • S.C. Ematologia, Ospedale di Circolo e Fondazione Macchi Varese, ASST dei Sette Laghi,

    Varese

  • U.O. di Ematologia Ospedale dell'Angelo Mestre

    Venezia

  • Istituti Ospitalieri di Verona Div. di Ematologia Policlinico G.B. Rossi

    Verona

  • U.O. Complessa di Ematologia Azienda ULSS 8 "Berica" Ospedale San Bortolo

    Vicenza

Other trials in Italy

Germany2 sites

  • Charité University of Berlin - Clinic of Medicine - Hematology and Oncology

    Berlin, 13353

  • University of Mannheim, Mannheim, Germania

    Mannheim

Other trials in Germany

Canada1 site

  • McGill University - Jewish General Hospital Division of Hematology and Department of Oncology

    Montreal, Quebec, H3T 1E2

Other trials in Canada

Spain1 site

  • University Hospital Clínic de Barcelona

    Barcelona

Other trials in Spain

About this study

Official title: Retro-prospective Observational Study on Risk of Progression in Chronic Phase-Chronic Myeloid Leukemia Patients Eligible for Tyrosine Kinase Inhibitor Discontinuation (TFR - PRO)

The purpose of this study is to investigate the safety profile of TKI discontinuation in clinical practice, with particular regard on the risk of progression after treatment discontinuation.

Read the detailed description

This study will enroll approximately 3000 CP-CML patients that must have a history of at least 4 years of TKI treatment and at least 18 months of DMR. Events developing in patients after the end of discontinuation and TKI resumption will be considered as linked to the discontinuation if they will develop within 36 months from the end of discontinuation. This rule will apply also to subsequent TD attempts. In case of a second or subsequent discontinuation attempt after the failure of a previous one (for molecular relapse), patients must have re-achieved a DMR with TKI therapy resumption and must keep DMR for at least 18 months before another TD.

Collection of data will be retrospective and prospective, as each center will collect the data for 24 months. Patients who discontinued before the opening of this study will contribute to the retrospective cohort, while those who will discontinue after it will contribute to the prospective cohort. Patients who discontinued before the opening of this study but will continue their discontinuation after it, will contribute to both cohorts. For patients prospectively recruited, monitoring of disease status will be performed to assess the maintenance of the molecular remission during the study period.

Patients with an atypical BCR-ABL1 fusion gene, which does not allow the use of Q-RT-PCR, will be monitored by qualitative PCR and will be analyzed separately. For these patients, negativity of nested qualitative RT-PCR will be considered a surrogate of DMR of patients monitored by Q-RT-PCR, while loss of negativity of first-round qualitative PCR will be considered a surrogate of loss of MMR (i.e. molecular relapse). Accordingly, for patients monitored by qualitative PCR, TKI resumption after TD will be provided in case of a new positivity of first-round PCR.

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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 groups in NCT04621851
Study groupRoleWhat they receive
Retrospective cohortPatients who discontinued before the opening of this study will contribute to the retrospective cohort.
Prospective cohortPatients who will discontinue after it will contribute to the prospective cohort.
Retrospective/Prospective cohortPatients who discontinued before the opening of this study but will continue their discontinuation after it, will contribute to both cohorts.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The quantification of the risk of progression

    To quantify the risk of progression to accelerated phase (AP) or blast phase (BP), expressed as time adjusted rate (TAR), after TKI discontinuation in CML patients who undergo a first or subsequent TKI discontinuation attempt

    Measured: 36 Month

Secondary outcomes (5)

  1. To compare the time adjusted rate (TAR) of progression from Chronic phase-Chronic Myeloid Leukemia to Accelerated phase (AP) or Blastic phase (BP) by using the percentage of blasts, promyelocytes, basophils or platelet in blood or bone marrow

    To compare the TAR (time adjusted rate) of progression to AP or BP that is obtained in the target population to that obtained in a similar population of patients with the same characteristics who do not discontinue TKI treatment

    Measured: 36 Month

  2. Progression free survival (PFS) after TKI discontinuation.

    PFS will be defined as time between discontinuation and progression to AP or BP.

    Measured: 36 Month

  3. Rate of molecular relapse (loss of MR3 or MMR)

    Rate of molecular relapse (loss of MR3 or MMR) at 12 and 24 months after TKI discontinuation.

    Measured: 36 Month

  4. Relapse free survival (RFS) after TKI discontinuation.

    Relapse free survival (RFS) after TKI discontinuation. RFS will be defined as time between discontinuation and loss of MMR (i.e. molecular relapse).

    Measured: 36 Month

  5. Percentage of relapsed patients who obtain a new deep molecular response (DMR) within 6-12 months of treatment resumption among all patients who restart TKI treatment because of a molecular relapse after TKI discontinuation.

    The following criteria will be used to define DMR (43):

    • MR4 = either (i) detectable disease with <0.01% BCR-ABL1IS or (ii) undetectable disease in cDNA with >10 000 ABL1 transcripts.
    • MR4.5 = either (i) detectable disease with <0.0032% BCR-ABL1IS or (ii) undetectable disease in cDNA with >32 000 ABL1 transcripts in the same volume of cDNA used to test for BCR-ABL1.
    • MR5 = either (i) detectable disease with <0.001% BCR-ABL1IS or (ii) undetectable disease in cDNA with >100 000 ABL1 transcripts in the same volume of cDNA used to test for BCR-ABL1.

    Measured: 36 Month

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Nov 2020
  2. Study start30 Sep 2020
  3. Primary completion30 Sep 2021
  4. Study completion14 Aug 2023

Resources

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
Other
Enrolment
260 participants (actual)
Target duration
36 Months
IDs, dates and publications
ClinicalTrials.gov ID
NCT04621851
Sponsor's protocol ID
TFR-PRO
Status last verified
Dec 2023
First submitted
14 Sep 2020
Last updated
29 Jul 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

An observational study of Chronic Myeloid Leukemia, run by University of Milano Bicocca at 26 sites in 4 countries.

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 5 inclusion and 2 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: finished, as of the sponsor's last update on 29 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in Italy, Germany, Canada, Spain. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The quantification of the risk of progression (time frame: 36 Month). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04621851.

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 29 Jul 2025.

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