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

Chronic Myeloid Leukemia Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04621851
• Other study ID #: TFR-PRO
• Status: Recruiting
• 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
• 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.

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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

Related Conditions & MeSH terms

• Chronic Myeloid Leukemia
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid

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