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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT02398825
Other study ID # CML1315
Secondary ID 2015-001102-34
Status Active, not recruiting
Phase Phase 2
First received
Last updated
Start date June 23, 2016
Est. completion date February 2023

Study information

Verified date August 2021
Source Gruppo Italiano Malattie EMatologiche dell'Adulto
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This study aims at evaluating the efficacy of treatment with ponatinib in patients with chronic myeloid leukemia who are in a chronic phase and who previously received treatment with imatinib but resulted to be resistant to it.


Description:

Phase 2, single-arm, multicentre, open label. No interim analysis is planned, but a monitoring committee will evaluate the data every 6 months. Ponatinib is given orally 30 mg daily, with dose adjustment to 15 mg daily once a BCR-ABL1 level smaller or equal to 0.1% (MMR) has been achieved and confirmed in the next test, 4 weeks apart. A return to prior, 30 mg, dose is due in case of return of BCR-ABL1 transcripts level to > 1%. Dose adjustments for toxicity are detailed in the protocol. Treatment time will be 52 weeks, during which study drug will be provided free-of-charge by ARIAD Pharmaceuticals, upon approval of the protocol. Treatment is discontinued at any time in case of failure or treatment-related SAEs. After one year of treatment, upon request of the local investigator and upon confirmation of the Treatment Advisory Committee (TAC, see section 23), ARIAD Pharmaceutics, Inc. will continue to provide ponatinib for the study patients who will benefit from treatment continuation, for at least 2 years, until the drug will be approved with that indication.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 16
Est. completion date February 2023
Est. primary completion date February 23, 2021
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: 1. Cytogenetic and/or molecular confirmed diagnosis of Ph+ and/or BCR-ABL1+ CML 2. Age = 18 years 3. Chronic phase CML 4. Prior treatment with imatinib, any dose 5. Resistance to imatinib, as defined by any one of the ELN 2013 failure criteria, as follows: - no complete hematologic response (CHR) at 3 months - no cytogenetic response (CyR) (Ph+ > 95%) at 3 months - Less than partial CyR (PCyR, Ph+ > 35%) at 6 months - BCR-ABL1 > 10% at 6 months - Non complete CyR (CCyR) (Ph+ > 0%) at 12 months - BCR-ABL1 > 1% at 12 months - Loss of CHR, at any time - Loss of CCyR, at any time - Confirmed loss of major molecular response (MMR) (BCR-ABL1 bigger or equal to 0.1% in two consecutive tests, of which one bigger or equal to 1%), at any time - Any new BCR-ABL1 mutation, at any time 6. For females of childbearing potential, a negative pregnancy test must be documented prior to enrolment 7. An effective form of contraception with their sexual partners from enrolment through 4 months after the end of treatment 8. Signed written informed consent according to ICH/EU/GCP and national local laws prior to any study procedures 9. Willingness and ability to comply with scheduled visits and study procedures. Exclusion Criteria: 1. Accelerated or blastic phase CML 2. Patients previously treated with nilotinib or dasatinib 3. Patients with the T315I mutation 4. History of acute pancreatitis within 1 year of study or history of chronic pancreatitis or of alcohol abuse 5. Patients with history of acute myocardial infarction (AMI), unstable angina or coronary heart disease (CHD), congestive heart failure, cerebrovascular events (CVE) (stroke or transitory ischemic attack), or peripheral artery occlusive disease (PAOD) 6. Compelled to take medications that are known to be associated with Torsades de Pointes and/or with significant QTc prolongation 7. Pregnant or breastfeeding 8. Any condition or illness that, in the opinion of the Investigator, would compromise patient safety or interfere with the evaluation of the drug 9. Lack of informed consent

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Ponatinib
Ponatinib is given orally 30 mg daily, with dose adjustment to 15 mg daily once a BCR-ABL1 level minor or equal to 0.1% (MMR) has been achieved and confirmed in the next test, 4 weeks apart. A return to prior, 30 mg, dose is due in case of return of BCR-ABL1 transcripts level to > 1%. Dose adjustments for toxicity are detailed in the protocol.

Locations

Country Name City State
Italy Aos Ss. Antonio E Biagio E C. Arrigo - Soc Ematologia Alessandria
Italy Azienda Ospedaliero - Universitaria Ospedali Riuniti Umberto I - G.M. Lancisi - G. Salesi Ancona
Italy Azienda Ospedaliera Di Bologna Policlinico S. Orsola - Malpighi Bologna
Italy Asst Degli Spedali Civili Di Brescia - Uo Ematologia Brescia
Italy Ao Brotzu, Presidio Ospedaliero A. Businco - Sc Ematologia E Ctmo Cagliari
Italy Ctc U.O Di Ematologia Con Trapianto Di Midollo Osseo Catania
Italy Università di Catania - Cattedra di Ematologia - Ospedale "Ferrarotto" Catania
Italy Ao Di Catanzaro "Pugliese-Ciaccio", Presidio Ospedaliero "Ciaccio - de Lellis" - Ematologia Catanzaro
Italy Aou Arcispedale Sant'Anna - Cona (Fe) - Uoc Ematologia E Fisiopatologia Della Coagulazione Cona
Italy Aso S. Croce E Carle - Cuneo - Sc Ematologia Cuneo
Italy Irccs Aou San Martino - Genova - Uo Clinica Ematologica Genova
Italy Asl Lecce, Ospedale 'V. Fazzi' - Uo Ematologia Lecce
Italy .R.S.T. Srl Irccs - Meldola - Sc Oncologia Medica Meldola
Italy Aou Policlinico "G. Martino" - Messina - Uoc Ematologia Messina
Italy Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico UOC Oncoematologia- Padiglione Marcora 2° piano Milano
Italy Irccs Ospedale S. Raffaele - Milano - Uo Oncoematologia Milano
Italy Milano Unità Trapianto di Midollo Ist. Nazionale Tumori Milano
Italy Ao Di Rilievo Nazionale Antonio Cardarelli - Napoli - Uoc Ematologia Con Trapianto Di Midollo Napoli
Italy Aou Federico Ii - Napoli - Uoc Ematologia Napoli
Italy Aou San Luigi Gonzaga - Orbassano - Scdu Ematologia Generale E Oncoematologia Orbassano
Italy Ao Ospedali Riuniti Villa Sofia Cervello - Palermo - Uo Ematologia Con Utmo Palermo
Italy Aou Policlinico P. Giaccone - Palermo - Uo Ematologia Palermo
Italy Fondazione Ircss Policlinico San Matteo - Pavia - Uo Ematologia Pavia
Italy Asl Pescara, Presidio Ospedaliero 'Spirito Santo' - Uoc Ematologia Clinica Pescara
Italy Unità Operativa Ematologia e Centro Trapianti - Dipartimento di Oncologia ed Ematologia - AUSL Ospedale G. da Saliceto Piacenza
Italy Aou Pisana - Uo Ematologia Universitaria Pisa
Italy Ausl Della Romagna, Ospedale "Santa Maria Delle Croci" - Ravenna - Ematologia Ravenna
Italy Ausl Della Romagna, Ospedale "Infermi" - Rimini - Uo Ematologia Rimini
Italy Ao San Camillo Forlanini - Roma - Uoc Ematologia E Trapianto Cellule Staminali Roma
Italy Asl Roma 2, Ospedale S. Eugenio- Ospedale S.Eugenio - Uoc Ematologia Roma
Italy Roma Uoc Pronto Soccorso E Accettazione Ematologica - Dipartimento Biotecnologie Cellulari Ed Ematologia - Università Degli Studi Di Roma "Sapienza" Roma
Italy Ente Ecclesiastico Casa Sollievo Della Sofferenza - San Giovanni Rotondo - Ematologia San Giovanni Rotondo
Italy Aou Senese - Uoc Ematologia E Trapianti Siena
Italy Ao S. Maria - Terni - Sc Onco Ematologia Terni
Italy Unità Operativa Di Ematologia - Presidio Ospedaliero Di Treviso - Azienda Ulss N.2 Marca Trevigiana Treviso
Italy Aou Integrata Di Verona, Policlinico G.B. Rossi - Uoc Ematologia Verona
Italy Aulss 8 Berica - Ospedale Di Vicenza - Uoc Ematologia Vicenza

Sponsors (1)

Lead Sponsor Collaborator
Gruppo Italiano Malattie EMatologiche dell'Adulto

Country where clinical trial is conducted

Italy, 

Outcome

Type Measure Description Time frame Safety issue
Primary Number of patients with major cytogenetic response Cytogenetic response (CyR) is defined based on the percentage of Ph pos metaphases, as evaluated by chromosome banding analysis (CBA) of at least 20 marrow cell metaphases:
Major Cytogenetic Response if Ph pos metaphases < 35%
Complete (CCyR) if Ph pos metaphases 0 or FISH BCR-ABL1 nuclei minor or equal to 1%
Partial (PCyR) if Ph pos metaphases 1-34%
Minor (mCyR) if Ph pos metaphases 35-65%
Minimal or none (min/none CyR) if Ph pos metaphases > 65% If marrow cell metaphases cannot be obtained or analysed, interphase fluorescence-in-situ-hybridization (FISH) can be used, but only to distinguish a CCyR (minor or equal to 1% positive nuclei out of at least 200 nuclei) from a non CCyR. FISH data cannot be used to classify a response as minimal, minor, or partial.
After 52 weeks of ponatinib treatment start
Secondary Number of Cardiovascular Adverse Events (AEs) After three years from ponatinib treatment start
Secondary Number of blood hypertension AEs After three years from ponatinib treatment start
Secondary Number of pancreatitis AEs After three years from ponatinib treatment start
Secondary Number of patients achieving Complete Cytogenetic Response (CCyR) After 52 weeks of ponatinib treatment start
Secondary Number of patients achieving major molecular response After 52 weeks of ponatinib treatment start
Secondary Number of patients with failure-free survival At 36 months from ponatinib treatment start
Secondary Number of patients with progression-free survival At 36 months from ponatinib treatment start
Secondary Number of patients in overal survival At 36 months from ponatinib treatment start
Secondary Number of patients in event-free survival At 36 months from ponatinib treatment start
Secondary Quality of Life patterns over time with the EORTC QLQ-C30 and the EORTC QLQ-CML24 questionnaires At baseline and at at weeks 4, 12, 24, 36 and 52
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