NCT02398825

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
14

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Jun 2016

Longer than P75 for phase_2

Geographic Reach
1 country

37 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 15, 2015

Completed
11 days until next milestone

First Posted

Study publicly available on registry

March 26, 2015

Completed
1.2 years until next milestone

Study Start

First participant enrolled

June 23, 2016

Completed
4.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 13, 2020

Completed
2.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 27, 2022

Completed
Last Updated

January 17, 2025

Status Verified

January 1, 2025

Enrollment Period

4.4 years

First QC Date

March 15, 2015

Last Update Submit

January 15, 2025

Conditions

Chronic Myeloid LeukemiaChronic PhaseAdults

Keywords

Chronic myeloid leukemiaChronic phaseAdultsPonatinibImatinib resistant

Outcome Measures

Primary Outcomes (1)

  • 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: 1. Major Cytogenetic Response if Ph pos metaphases \< 35% 2. Complete (CCyR) if Ph pos metaphases 0 or FISH BCR-ABL1 nuclei minor or equal to 1% 3. Partial (PCyR) if Ph pos metaphases 1-34% 4. Minor (mCyR) if Ph pos metaphases 35-65% 5. 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 Outcomes (10)

  • Number of Cardiovascular Adverse Events (AEs)

    After three years from ponatinib treatment start

  • Number of blood hypertension AEs

    After three years from ponatinib treatment start

  • Number of pancreatitis AEs

    After three years from ponatinib treatment start

  • Number of patients achieving Complete Cytogenetic Response (CCyR)

    After 52 weeks of ponatinib treatment start

  • Number of patients achieving major molecular response

    After 52 weeks of ponatinib treatment start

  • +5 more secondary outcomes

Study Arms (1)

Ponatinib

EXPERIMENTAL
Drug: Ponatinib

Interventions

PonatinibDRUG

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.

Ponatinib

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Cytogenetic and/or molecular confirmed diagnosis of Ph+ and/or BCR-ABL1+ CML
  • Age ≥ 18 years
  • Chronic phase CML
  • Prior treatment with imatinib, any dose
  • 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
  • +4 more criteria

You may not qualify if:

  • Accelerated or blastic phase CML
  • Patients previously treated with nilotinib or dasatinib
  • Patients with the T315I mutation
  • History of acute pancreatitis within 1 year of study or history of chronic pancreatitis or of alcohol abuse
  • 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)
  • Compelled to take medications that are known to be associated with Torsades de Pointes and/or with significant QTc prolongation
  • Pregnant or breastfeeding
  • Any condition or illness that, in the opinion of the Investigator, would compromise patient safety or interfere with the evaluation of the drug
  • Lack of informed consent

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (37)

Aos Ss. Antonio E Biagio E C. Arrigo - Soc Ematologia

Alessandria, Italy

Location

Azienda Ospedaliero - Universitaria Ospedali Riuniti Umberto I - G.M. Lancisi - G. Salesi

Ancona, Italy

Location

Azienda Ospedaliera Di Bologna Policlinico S. Orsola - Malpighi

Bologna, 40138, Italy

Location

Asst Degli Spedali Civili Di Brescia - Uo Ematologia

Brescia, Italy

Location

Ao Brotzu, Presidio Ospedaliero A. Businco - Sc Ematologia E Ctmo

Cagliari, Italy

Location

Ctc U.O Di Ematologia Con Trapianto Di Midollo Osseo

Catania, Italy

Location

Università di Catania - Cattedra di Ematologia - Ospedale "Ferrarotto"

Catania, Italy

Location

Ao Di Catanzaro "Pugliese-Ciaccio", Presidio Ospedaliero "Ciaccio - de Lellis" - Ematologia

Catanzaro, Italy

Location

Aou Arcispedale Sant'Anna - Cona (Fe) - Uoc Ematologia E Fisiopatologia Della Coagulazione

Cona, Italy

Location

Aso S. Croce E Carle - Cuneo - Sc Ematologia

Cuneo, Italy

Location

Irccs Aou San Martino - Genova - Uo Clinica Ematologica

Genova, Italy

Location

Asl Lecce, Ospedale 'V. Fazzi' - Uo Ematologia

Lecce, Italy

Location

.R.S.T. Srl Irccs - Meldola - Sc Oncologia Medica

Meldola, Italy

Location

Aou Policlinico "G. Martino" - Messina - Uoc Ematologia

Messina, Italy

Location

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico UOC Oncoematologia- Padiglione Marcora 2° piano

Milan, Italy

Location

Irccs Ospedale S. Raffaele - Milano - Uo Oncoematologia

Milan, Italy

Location

Milano Unità Trapianto di Midollo Ist. Nazionale Tumori

Milan, Italy

Location

Ao Di Rilievo Nazionale Antonio Cardarelli - Napoli - Uoc Ematologia Con Trapianto Di Midollo

Napoli, Italy

Location

Aou Federico Ii - Napoli - Uoc Ematologia

Napoli, Italy

Location

Aou San Luigi Gonzaga - Orbassano - Scdu Ematologia Generale E Oncoematologia

Orbassano, Italy

Location

Ao Ospedali Riuniti Villa Sofia Cervello - Palermo - Uo Ematologia Con Utmo

Palermo, Italy

Location

Aou Policlinico P. Giaccone - Palermo - Uo Ematologia

Palermo, Italy

Location

Fondazione Ircss Policlinico San Matteo - Pavia - Uo Ematologia

Pavia, Italy

Location

Asl Pescara, Presidio Ospedaliero 'Spirito Santo' - Uoc Ematologia Clinica

Pescara, Italy

Location

Unità Operativa Ematologia e Centro Trapianti - Dipartimento di Oncologia ed Ematologia - AUSL Ospedale G. da Saliceto

Piacenza, Italy

Location

Aou Pisana - Uo Ematologia Universitaria

Pisa, Italy

Location

Ausl Della Romagna, Ospedale "Santa Maria Delle Croci" - Ravenna - Ematologia

Ravenna, Italy

Location

Ausl Della Romagna, Ospedale "Infermi" - Rimini - Uo Ematologia

Rimini, Italy

Location

Ao San Camillo Forlanini - Roma - Uoc Ematologia E Trapianto Cellule Staminali

Roma, Italy

Location

Asl Roma 2, Ospedale S. Eugenio- Ospedale S.Eugenio - Uoc Ematologia

Roma, Italy

Location

Roma Uoc Pronto Soccorso E Accettazione Ematologica - Dipartimento Biotecnologie Cellulari Ed Ematologia - Università Degli Studi Di Roma "Sapienza"

Roma, Italy

Location

Ente Ecclesiastico Casa Sollievo Della Sofferenza - San Giovanni Rotondo - Ematologia

San Giovanni Rotondo, Italy

Location

Aou Senese - Uoc Ematologia E Trapianti

Siena, Italy

Location

Ao S. Maria - Terni - Sc Onco Ematologia

Terni, Italy

Location

Unità Operativa Di Ematologia - Presidio Ospedaliero Di Treviso - Azienda Ulss N.2 Marca Trevigiana

Treviso, Italy

Location

Aou Integrata Di Verona, Policlinico G.B. Rossi - Uoc Ematologia

Verona, Italy

Location

Aulss 8 Berica - Ospedale Di Vicenza - Uoc Ematologia

Vicenza, Italy

Location

Related Links

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

ponatinib

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsMyeloproliferative DisordersBone Marrow DiseasesHematologic DiseasesHemic and Lymphatic DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Fausto Castagnetti

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

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 15, 2015

First Posted

March 26, 2015

Study Start

June 23, 2016

Primary Completion

November 13, 2020

Study Completion

December 27, 2022

Last Updated

January 17, 2025

Record last verified: 2025-01

Locations

IT(37)