Clinical trial NCT04621851: Retro-prospective Observational Study on Risk of Progression in CP-CML Patients Eligible for TKI Discontinuation
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)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Chronic Myeloid Leukemia
Lead sponsor: University of Milano Bicocca
Sponsor class: OTHER
First posted: 2020-11-09
Enrollment: 3000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: PROBABILITY_SAMPLE
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.

Brief 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.

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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Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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

Primary outcomes:
measure: The quantification of the risk of progression
timeFrame: 36 Month
Secondary outcomes:
measure: 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
timeFrame: 36 Month
measure: Progression free survival (PFS) after TKI discontinuation.
timeFrame: 36 Month
measure: Rate of molecular relapse (loss of MR3 or MMR)
timeFrame: 36 Month
measure: Relapse free survival (RFS) after TKI discontinuation.
timeFrame: 36 Month
measure: 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.
timeFrame: 36 Month
Other outcomes:
Locations:
city: Montréal
country: Canada
facility: McGill University - Jewish General Hospital Division of Hematology and Department of Oncology
state: Quebec
city: Berlin
country: Germany
facility: Charité University of Berlin - Clinic of Medicine - Hematology and Oncology
city: Mannheim
country: Germany
facility: University of Mannheim, Mannheim, Germania
city: Monza
country: Italy
facility: ASST-Monza
state: Italy/MB
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico UOC di Ematologia
state: Italy/Milano
city: Rome
country: Italy
facility: Universita di Tor Vergata Ospedale S. Eugenio
state: Italy/Rome
city: Bologna
country: Italy
facility: Istituto di Ematologia "Lorenzo e A. Seragnoli" Policlinico S. Orsola Malpighi,
city: Cagliari
country: Italy
facility: CTMO Ematologia Ospedale "Businco"
city: Catania
country: Italy
facility: Università di Catania Cattedra di Ematologia Ospedale "Ferrarotto"
city: Catanzaro
country: Italy
facility: SOC Ematologia Az. Ospedaliera Pugliese Ciaccio (AOPC)
city: Cuneo
country: Italy
facility: Ematologia Ospedale Cuneo
city: Miano
country: Italy
facility: UO Ematologia O spedale Milano S. Raffaele
city: Napoli
country: Italy
facility: Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli"
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Università degli Studi di Napoli "Federico II" Facoltà di Medicina e Chirurgia
city: Palermo
country: Italy
facility: U.O. di Ematologia con trapianto A.U. Policlinico "Paolo Giaccone"
city: Parma
country: Italy
facility: Unità operativa Ematologia e CTMO Az Ospedaliera Universitaria
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Pisa
country: Italy
facility: Università di Pisa Azienda Ospedaliera Pisana Divisione di Ematologia
city: Reggio Emilia
country: Italy
facility: Azienda Unità Sanitaria Locale IRCCS
city: Torino
country: Italy
facility: Dipartimento di Oncologia ed Ematologia S.C. Ematologia 2 A.O. Città della Salute e della Scienza di Torino S. G.Battista
city: Torino
country: Italy
facility: Struttura Complessa a Dir. Universitaria Ematologia e Terapie Cellulari A.S.O. Ordine Mauriziano, P.O. U mberto I
city: Varese
country: Italy
facility: S.C. Ematologia, Ospedale di Circolo e Fondazione Macchi Varese, ASST dei Sette Laghi,
city: Venezia
country: Italy
facility: U.O. di Ematologia Ospedale dell'Angelo Mestre
city: Verona
country: Italy
facility: Istituti Ospitalieri di Verona Div. di Ematologia Policlinico G.B. Rossi
city: Vicenza
country: Italy
facility: U.O. Complessa di Ematologia Azienda ULSS 8 "Berica" Ospedale San Bortolo
city: Barcelona
country: Spain
facility: University Hospital Clínic de Barcelona
Study officials:
affiliation: Ospedale S. Eugenio Roma
name: Elisabetta Abruzzese, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: A.U. Policlinico "Paolo Giaccone" Palermo
name: Vincenzo Accurso, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli" Napoli
name: Mario Annunziata, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale di Circolo e Fondazione Macchi Varese, ASST dei Sette Laghi Varese
name: Francesco Passamonti, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Istituti Ospitalieri di Verona- Policlinico G.B. Rossi Verona
name: Massimo Bonifacio, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CTMO - Ospedale "Businco" Cagliari
name: Giovanni Caocci, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale Milano S. Raffaele Milano
name: Francesca Lunghi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fondazione IRCCS Policlinico San Matteo di Pavia
name: Chiara Elena, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Az Ospedaliera Universitaria Parma
name: Monica Crugnola, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Azienda Ospedaliera Pisana Pisa
name: Sara Galimberti, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano Milano
name: Alessandra Iurlo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Az. Ospedaliera Pugliese - Ciaccio (AOPC) Catanzaro
name: Luciano Levato, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Azienda ULSS 8 "Berica" Ospedale San Bortolo Vicenza
name: Maria Cristina Miggiano, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: A.O. Città della Salute e della Scienza di Torino S. G.Battista Torino
name: Patrizia Pregno, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale Cuneo
name: Davide Rapezzi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale dell'Angelo Mestre Venezia
name: Rosaria Sancetta, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: P.O. Gaspare Rodolico, Catania
name: Fabio Stagno, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Azienda Ospedaliera Universitaria-Università degli Studi di Napoli "Federico II"
name: Luigia Luciano, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: A.S.O. Ordine Mauriziano, P.O. Umberto I Torino
name: Carmen Fava, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Charité University of Berlin · Medical Department, Division of Oncology and Hematology
name: Philipp leCoutre, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Mannheim
name: Susanne Saussele, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Jewish General Hospital
name: Sarit Assouline, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Clínic de Barcelona
name: Alberto Álvarez-Larrán, MD
role: PRINCIPAL_INVESTIGATOR
References: