Activity and Risk Profile of Ponatinib in Chronic Phase Patients With Chronic Myeloid Leukemia Resistant to Imatinib

NCT ID: NCT02398825

Last Updated: 2025-01-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-23
• Study Completion Date: 2022-12-27

Brief 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.

Detailed 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.

Conditions

Chronic Myeloid Leukemia; Chronic Phase; Adults

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ponatinib

Group Type: EXPERIMENTAL

Ponatinib

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gruppo Italiano Malattie EMatologiche dell'Adulto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Fausto Castagnetti

Role: STUDY_CHAIR

Department of Hematology, S. Orsola-Malpighi University of Bologna

Locations

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

Milan, , Italy

Irccs Ospedale S. Raffaele - Milano - Uo Oncoematologia

Milan, , Italy

Milano Unità Trapianto di Midollo Ist. Nazionale Tumori

Milan, , 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, , Italy

Countries

Italy

Related Links

http://www.gimema.it

GIMEMA Foundation

Other Identifiers

2015-001102-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CML1315

Identifier Type: -

Identifier Source: org_study_id