Clinical Trials /

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

NCT02398825

Description:

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.

Related Conditions:
  • Chronic Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Activity and Risk Profile of Ponatinib in Chronic Phase Patients With Chronic Myeloid Leukemia Resistant to Imatinib
  • Official Title: Optimizing Ponatinib USe (OPUS). A GIMEMA Phase 2 Study of the Activity and Risk Profile of Ponatinib, 30 mg Once Daily, in Chronic Myeloid Leukemia (CML) Chronic Phase (CP) Patients Resistant to Imatinib

Clinical Trial IDs

  • ORG STUDY ID: CML1315
  • SECONDARY ID: 2015-001102-34
  • NCT ID: NCT02398825

Conditions

  • Chronic Myeloid Leukemia
  • Chronic Phase
  • Adults

Interventions

DrugSynonymsArms
PonatinibPonatinib

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
PonatinibExperimental
  • Ponatinib

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of patients with major cytogenetic response
Time Frame:After 52 weeks of ponatinib treatment start
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Number of Cardiovascular Adverse Events (AEs)
Time Frame:After three years from ponatinib treatment start
Safety Issue:
Description:
Measure:Number of blood hypertension AEs
Time Frame:After three years from ponatinib treatment start
Safety Issue:
Description:
Measure:Number of pancreatitis AEs
Time Frame:After three years from ponatinib treatment start
Safety Issue:
Description:
Measure:Number of patients achieving Complete Cytogenetic Response (CCyR)
Time Frame:After 52 weeks of ponatinib treatment start
Safety Issue:
Description:
Measure:Number of patients achieving major molecular response
Time Frame:After 52 weeks of ponatinib treatment start
Safety Issue:
Description:
Measure:Number of patients with failure-free survival
Time Frame:At 36 months from ponatinib treatment start
Safety Issue:
Description:
Measure:Number of patients with progression-free survival
Time Frame:At 36 months from ponatinib treatment start
Safety Issue:
Description:
Measure:Number of patients in overal survival
Time Frame:At 36 months from ponatinib treatment start
Safety Issue:
Description:
Measure:Number of patients in event-free survival
Time Frame:At 36 months from ponatinib treatment start
Safety Issue:
Description:
Measure:Quality of Life patterns over time with the EORTC QLQ-C30 and the EORTC QLQ-CML24 questionnaires
Time Frame:At baseline and at at weeks 4, 12, 24, 36 and 52
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Gruppo Italiano Malattie EMatologiche dell'Adulto

Trial Keywords

  • Chronic myeloid leukemia
  • Chronic phase
  • Adults
  • Ponatinib
  • Imatinib resistant

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