A Phase 2 interventional study of Ponatinib in Leukemia, Myeloid, Chronic-Phase, sponsored by GWT-TUD GmbH. Terminated at 10 sites in Germany. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-09-14.
Sponsored by GWT-TUD GmbH · Phase 2, Interventional, and 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.
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.
5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.
This study's enrollment of 18 is below the median of 38 across 4,247 interventional studies indexed under Leukemia.
Browse Leukemia studies →GWT-TUD GmbH is the lead sponsor of 39 studies on the registry; none are open to participants now.
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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:
Exclusion Criteria:
Patients 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.
Drug: Ponatinib
2 film-coated tablets à 15mg for oral administration on a daily basis
Also known as: Iclusig
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.
Time frame: by 12 moths
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.
Time frame: up to 24 months
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).
Time frame: at 3, 6, 9, 12, 18 and 24 months
Durations of response
To evaluate the duration of hematologic, cytogenetic and molecular response to Ponatinib after one TKI failure.
Time frame: at 3, 6, 9, 12, 18 and 24 month
Occurrence of BCR-ABL-mutations
To evaluate the occurrence of BCR-ABL-mutations in patients with failure of Ponatinib 2nd line therapy.
Time frame: at 3, 6, 9, 12, 18 and 24 months
Time to progression
To define the time to progression for patients with CML in chronic phase treated with Ponatinib after one TKI failure.
Time frame: at 3, 6, 9, 12, 18 and 24 months
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.
Time frame: at 3, 6, 9, 12, 18 and 24 month
Plan to share: No
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This study is terminated, as verified in Sep 2022. You cannot join it, but the record below documents what was studied.
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GWT-TUD GmbH