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JOURNAL ONKOLOGIE – STUDIE

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

Rekrutierend

NCT-Nummer:
NCT04621851

Studienbeginn:
September 2020

Letztes Update:
09.11.2020

Wirkstoff:
-

Indikation (Clinical Trials):
Leukemia, Leukemia, Myeloid, Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
University of Milano Bicocca

Collaborator:
-

Studienleiter

Elisabetta Abruzzese, MD
Principal Investigator
Ospedale S. Eugenio Roma
Vincenzo Accurso, MD
Principal Investigator
A.U. Policlinico "Paolo Giaccone" Palermo
Mario Annunziata, MD
Principal Investigator
Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli" Napoli
Francesco Passamonti, MD
Principal Investigator
Ospedale di Circolo e Fondazione Macchi Varese, ASST dei Sette Laghi Varese
Massimo Bonifacio, MD
Principal Investigator
Istituti Ospitalieri di Verona- Policlinico G.B. Rossi Verona
Giovanni Caocci, MD
Principal Investigator
CTMO - Ospedale "Businco" Cagliari
Francesca Lunghi, MD
Principal Investigator
Ospedale Milano S. Raffaele Milano
Chiara Elena, MD
Principal Investigator
Policlinico San Matteo Pavia Fondazione IRCCS
Monica Crugnola, MD
Principal Investigator
Az Ospedaliera Universitaria Parma
Sara Galimberti, MD
Principal Investigator
Azienda Ospedaliera Pisana Pisa
Alessandra Iurlo, MD
Principal Investigator
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano Milano
Luciano Levato, MD
Principal Investigator
Az. Ospedaliera Pugliese - Ciaccio (AOPC) Catanzaro
Maria Cristina Miggiano, MD
Principal Investigator
Azienda ULSS 8 "Berica" Ospedale San Bortolo Vicenza
Patrizia Pregno, MD
Principal Investigator
A.O. Città della Salute e della Scienza di Torino S. G.Battista Torino
Davide Rapezzi, MD
Principal Investigator
Ospedale Cuneo
Rosaria Sancetta, MD
Principal Investigator
Ospedale dell'Angelo Mestre Venezia
Fabio Stagno, MD
Principal Investigator
P.O. Gaspare Rodolico, Catania
Luigia Luciano, MD
Principal Investigator
Azienda Ospedaliera Universitaria-Università degli Studi di Napoli "Federico II"
Carmen Fava, MD
Principal Investigator
A.S.O. Ordine Mauriziano, P.O. Umberto I Torino
Philipp leCoutre, MD
Principal Investigator
Charité University of Berlin · Medical Department, Division of Oncology and Hematology
Susanne Saussele, MD
Principal Investigator
University of Mannheim
Sarit Assouline, MD
Principal Investigator
Jewish General Hospital
Alberto Álvarez-Larrán, MD
Principal Investigator
University Hospital Clínic de Barcelona

Kontakt

Studienlocations (3 von 26)

Charité University of Berlin - Clinic of Medicine - Hematology and Oncology
13353 Berlin
(Berlin)
GermanyNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Philipp le Coutre, MD
Phone: +49 30 450553077
E-Mail: philipp.lecoutre@charite.de
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McGill University - Jewish General Hospital Division of Hematology and Department of Oncology
H3T 1E2 Montréal
CanadaNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Sarit Assouline, MD
Phone: 001 514 3408207
E-Mail: sarit.assouline@mcgill.ca
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Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico UOC di Ematologia
20162 Milano
ItalyNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Alessandra Iurlo
Phone: +390255033362
E-Mail: aiurlo@policlinico.mi.it
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Azienda Ospedaliera Universitaria Università degli Studi di Napoli "Federico II" Facoltà di Medicina e Chirurgia
Napoli
ItalyNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Luigia Luciani
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Dipartimento di Oncologia ed Ematologia S.C. Ematologia 2 A.O. Città della Salute e della Scienza di Torino S. G.Battista
Torino
ItalyNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Patrizia Pregno
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Struttura Complessa a Dir. Universitaria Ematologia e Terapie Cellulari A.S.O. Ordine Mauriziano, P.O. U mberto I
Torino
ItalyNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Carmen Fava
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Alle anzeigen

Studien-Informationen

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.

.

Ein-/Ausschlusskriterien

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

Studien-Rationale

Primary outcome:

1. The quantification of the risk of progression (Time Frame - 36 Month):
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



Secondary outcome:

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 (Time Frame - 36 Month):
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

2. Progression free survival (PFS) after TKI discontinuation. (Time Frame - 36 Month):
PFS will be defined as time between discontinuation and progression to AP or BP.

3. Rate of molecular relapse (loss of MR3 or MMR) (Time Frame - 36 Month):
Rate of molecular relapse (loss of MR3 or MMR) at 12 and 24 months after TKI discontinuation.

4. Relapse free survival (RFS) after TKI discontinuation. (Time Frame - 36 Month):
Relapse free survival (RFS) after TKI discontinuation. RFS will be defined as time between discontinuation and loss of MMR (i.e. molecular relapse).

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. (Time Frame - 36 Month):
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.

Studien-Arme

  • Retrospective cohort
    Patients who discontinued before the opening of this study will contribute to the retrospective cohort.
  • Prospective cohort
    Patients who will discontinue after it will contribute to the prospective cohort.
  • Retrospective/Prospective cohort
    Patients who discontinued before the opening of this study but will continue their discontinuation after it, will contribute to both cohorts.

Quelle: ClinicalTrials.gov


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