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Leukemia, Myeloid, Chronic-PhasePhase 2PONSNCT03807479

Study in Patients With Chronic Leukemia

A Phase 2 study testing Ponatinib in people with Leukemia, Myeloid, Chronic-Phase, run by GWT-TUD GmbH at 10 sites in Germany.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This study will include patients suffering from chronic myeloid leukemia (CP-CML), who were treated with tyrosine kinase inhibitor (TKI, a substance that blocks the action of enzymes) in a previous therapy but which has not been effective. Patients will be treated with Ponatinib 30 mg in in this study. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Leukemia, Myeloid, Chronic-Phase
What is being tested?
Ponatinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
10 sitesGermany
Study dates
11 Dec 2018to 31 Aug 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female patients ≥18 years old
  • Diagnosis of Ph-positive (by cytogenetics) or BCR-ABL-positive (by PCR) CP-CML
  • Patients should have demonstrated to have
  • a failure of a prior 1st line TKI treatment with either imatinib, dasatinib or nilotinib. Failure is defined as per European LeukemiaNet (ELN) recommendations:
  • Less than Complete Hematologic Response (CHR) and/or Ph+ > 95% at or beyond 3 months
  • No cytogenetic response (Ph+>35%) and/or Abelson murine leukemia viral oncogene homolog 1 (BCR-ABL1) >10% at or beyond 6 months
Show all 11Show fewer
  • BCR-ABL (on international scale) >1% and/or PH+ >0%
  • Less than MMR at or beyond 18 months
  • Loss of response or development of mutations or other clonal chromosomal abnormalities at any time during the first line TKI treatment
  • or intolerance to prior TKI treatment defined as grade 3 or 4 toxicity, or persistent grade 2 toxicity despite optimal management including dose adjustment, or in a patient where dose reductions are considered to be not in the patient's best interest to obtain an adequate response. Intolerant patients should not have achieved or have lost major molecular response at the time of enrollment
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

Who cannot join

  • Any 1st line anti-CML treatment other than TKI (apart from therapy with hydroxyurea)
  • Any 2nd line therapy with a tyrosine kinase inhibitor (>1 European Medicines Agency (EMA) approved TKI for CML, or any investigational non EMA-approved TKI)
  • Concurrent participation in any other clinical trial involving another investigational drug within 4 weeks prior to enrollment and throughout participation in PONS-Study
  • New York Heart Association (NYHA) cardiac class 3-4 heart disease
  • Cardiac Symptoms within the past 12 months prior recruitment

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

Germany10 sites

  • University Hospital RWTH Aachen,Clinic for Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Department IV

    Aachen, 52074

  • Charité University Medicine Berlin - Medical Clinic, Department of Hematology, Oncology and Tumor Immunology

    Berlin, 13353

  • University Hospital Essen gGmbH, Westdeutsches Tumorzentrum; Internal Medicine (Tumor Research)

    Essen, 45122

  • University Medicine Greifswald, Clinic and Policlinic - Internal Medicine C - Hematology and Oncology

    Greifswald, 17475

  • University Hospital

    Halle, Saxony-Anhalt, 06097

  • Asklepios Clinic St. Georg - Department of Oncology, Section Hematology

    Hamburg, 20099

  • University Hospital Mannheim GmbH, III. Medical Clinic for Hematology and Oncology

    Mannheim, 68167

  • Clinic for Hematologie

    Marburg, 35043

  • UKRUB University Hospital of Ruhr-University Bochum, Clinic for Hematology and Oncology

    Minden, 32429

  • University Hospital Ulm - Department for internal medicine III

    Ulm, 89081

Other trials in Germany

About this study

Official title: Phase 2 Clinical Trial With Ponatinib as a Second Line Therapy for Patients With Chronic Myeloid Leukemia in Chronic Phase Resistant or Intolerant to Prior First Line Tyrosine Kinase Inhibitor Treatment

This study will include patients suffering from chronic myeloid leukemia (CP-CML), who were treated with tyrosine kinase inhibitor (TKI, a substance that blocks the action of enzymes) in a previous therapy but which has not been effective. Patients will be treated with Ponatinib 30 mg in in this study. The aim of the study is to evaluate the safety and efficacy of Ponatinib as a second line treatment in patients failing or not tolerating first line therapy with any other approved TKIs. It is expected that Ponatinib, due to its efficacy, may be more effective as second line therapy than other approved TKIs and lead to improved overall survival. The effect will be determined by the molecular response rate (MMR) as the primary objective after 12 months of treatment. The safety of the drug will be evaluated on the basis if routine medical and laboratory examinations.

Read the detailed description

Despite significant progress in the treatment of patients with chronic phase CML, there is still need to further optimize therapy to reach the goal of disease eradication for almost all patients. In case of imatinib failure, dasatinib and nilotinib are effective treatment options after an individualized treatment selection. Although MMR rates of around 30% after 2 years of therapy are a significant achievement, options that may improve response rates in depth are still desirable. Ponatinib is a third generation TKI with very high anti-clonal activity in all CML phases. Moreover, it also eradicates most of the known and problematic mutations and only very few (compound) mutations may induce ponatinib-resistance.

Based on its favourable target spectrum, it is expected that Ponatinib may be more effective than 2nd line dasatinib or nilotinib in achieving early (i.e., at 6 months) cytogenetic and molecular responses in patients after inappropriate response to imatinib, and more effective as 2nd line treatment after failure of initial treatment with dasatinib or nilotinib than a cross-over between the 2nd generation TKIs. The basic hypothesis underlying therapeutic programs in CML is to be able to achieve meaningful and long-lasting suppression of the Philadelphia chromosome and breakpoint cluster region-abelson fusion gen (BCR-ABL). Complete cytogenetic responses have been associated with improved survival in CML, while major molecular responses are associated with improved event-free survival.

Being tested
Ponatinib
Keywords
CP-CML, CML in chronic phase, Chronic Myelogenous Leukemia, Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Medical subject headings
Leukemia, Myeloid, Chronic-Phase, Leukemia, Myelogenous, Chronic, BCR-ABL Positive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PonatinibDrug

    Also called Iclusig

    2 film-coated tablets à 15mg for oral administration on a daily basis

Study groups in NCT03807479
Study groupRoleWhat they receive
PonatinibExperimentalPatients in this treatment arm receive Ponatinib: starting dose 30 mg once-daily. Doses may be increased in case of inappropriate response and reduced to manage drug-related adverse events (AEs) and may be re-escalated once events resolve.
Receives: Drug: Ponatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Major Molecular Response (MMR) of treatment

    To estimate the proportion of CP-CML patients with tyrosine kinase inhibitor (TKI)-resistance or intolerance to first line therapy with TKI, attaining MMR by 12 months of treatment with second line Ponatinib therapy.

    Measured: by 12 moths

Secondary outcomes (6)

  1. Time to toxicity

    To evaluate the toxicity profile of ponatinib in patients with CML in chronic phase after one TKI failure toxicities will be followed up at each visit during the treatment phase and will be assessed using CTCAE v.5.0. Type of toxicity (hematologic or non-hematologic) along with the grading will be followed up on.

    Measured: up to 24 months

  2. Time to response

    To estimate the time to CCyR, MMR, MCyR and MR4 for patients treated with Ponatinib as second line therapy for CP-CML (chronic phase-chronic myelogenous leukemia).

    Measured: at 3, 6, 9, 12, 18 and 24 months

  3. Durations of response

    To evaluate the duration of hematologic, cytogenetic and molecular response to Ponatinib after one TKI failure.

    Measured: at 3, 6, 9, 12, 18 and 24 month

  4. Occurrence of BCR-ABL-mutations

    To evaluate the occurrence of BCR-ABL-mutations in patients with failure of Ponatinib 2nd line therapy.

    Measured: at 3, 6, 9, 12, 18 and 24 months

  5. Time to progression

    To define the time to progression for patients with CML in chronic phase treated with Ponatinib after one TKI failure.

    Measured: at 3, 6, 9, 12, 18 and 24 months

  6. Time to overall survival

    To define the time to overall survival for patients with CML in chronic phase treated with Ponatinib after one TKI failure.

    Measured: at 3, 6, 9, 12, 18 and 24 month

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jan 2019
  2. Study start11 Dec 2018
  3. Primary completion28 Feb 2023
  4. Study completion31 Aug 2023

Why it stopped: less recruting

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03807479
Sponsor's protocol ID
PONS_11272
Acronym
PONS
Status last verified
Sep 2022
First submitted
7 Nov 2018
Last updated
14 Sep 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ponatinib in people with Leukemia, Myeloid, Chronic-Phase, run by GWT-TUD GmbH at 10 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 14 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: less recruting). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Major Molecular Response (MMR) of treatment (time frame: by 12 moths). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03807479.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2023.

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