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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04621851
Other study ID # TFR-PRO
Secondary ID
Status Recruiting
Phase
First received
Last updated
Start date September 30, 2020
Est. completion date September 30, 2023

Study information

Verified date July 2022
Source University of Milano Bicocca
Contact CARLO GAMBACORTI PASSERINI
Phone +39 233.9553
Email carlo.gambacorti@unimib.it
Is FDA regulated No
Health authority
Study type Observational [Patient Registry]

Clinical 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.


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. .


Recruitment information / eligibility

Status Recruiting
Enrollment 3000
Est. completion date September 30, 2023
Est. primary completion date September 30, 2021
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Related Conditions & MeSH terms


Locations

Country Name City State
Canada McGill University - Jewish General Hospital Division of Hematology and Department of Oncology Montréal Quebec
Germany Charité University of Berlin - Clinic of Medicine - Hematology and Oncology Berlin
Germany University of Mannheim, Mannheim, Germania Mannheim
Italy Istituto di Ematologia "Lorenzo e A. Seragnoli" Policlinico S. Orsola Malpighi, Bologna
Italy CTMO Ematologia Ospedale "Businco" Cagliari
Italy Università di Catania Cattedra di Ematologia Ospedale "Ferrarotto" Catania
Italy SOC Ematologia Az. Ospedaliera Pugliese Ciaccio (AOPC) Catanzaro
Italy Ematologia Ospedale Cuneo Cuneo
Italy UO Ematologia O spedale Milano S. Raffaele Miano
Italy Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico UOC di Ematologia Milano Italy/Milano
Italy ASST-Monza Monza Italy/MB
Italy Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli" Napoli
Italy Azienda Ospedaliera Universitaria Università degli Studi di Napoli "Federico II" Facoltà di Medicina e Chirurgia Napoli
Italy U.O. di Ematologia con trapianto A.U. Policlinico "Paolo Giaccone" Palermo
Italy Unità operativa Ematologia e CTMO Az Ospedaliera Universitaria Parma
Italy Fondazione IRCCS Policlinico San Matteo Pavia
Italy Università di Pisa Azienda Ospedaliera Pisana Divisione di Ematologia Pisa
Italy Azienda Unità Sanitaria Locale IRCCS Reggio Emilia
Italy Universita di Tor Vergata Ospedale S. Eugenio Rome Italy/Rome
Italy Dipartimento di Oncologia ed Ematologia S.C. Ematologia 2 A.O. Città della Salute e della Scienza di Torino S. G.Battista Torino
Italy Struttura Complessa a Dir. Universitaria Ematologia e Terapie Cellulari A.S.O. Ordine Mauriziano, P.O. U mberto I Torino
Italy S.C. Ematologia, Ospedale di Circolo e Fondazione Macchi Varese, ASST dei Sette Laghi, Varese
Italy U.O. di Ematologia Ospedale dell'Angelo Mestre Venezia
Italy Istituti Ospitalieri di Verona Div. di Ematologia Policlinico G.B. Rossi Verona
Italy U.O. Complessa di Ematologia Azienda ULSS 8 "Berica" Ospedale San Bortolo Vicenza
Spain University Hospital Clínic de Barcelona Barcelona

Sponsors (1)

Lead Sponsor Collaborator
University of Milano Bicocca

Countries where clinical trial is conducted

Canada,  Germany,  Italy,  Spain, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 36 Month
Secondary 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 36 Month
Secondary Progression free survival (PFS) after TKI discontinuation. PFS will be defined as time between discontinuation and progression to AP or BP. 36 Month
Secondary 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. 36 Month
Secondary 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). 36 Month
Secondary 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.
36 Month
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