Study in Patients With Chronic Leukemia, Where Previous Therapy Failed, and Who Will be Treated With Ponatinib as Second Line Therapy

• Status: Recruiting
• Trial end date: 2024-05-01
• Target enrollment: 0
• Participant gender: All

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. 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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: GWT-TUD GmbH
• Collaborator: Incyte Biosciences International Sàrl
• Treatments: Ponatinib

Criteria

Inclusion Criteria:

1. Male or female patients ≥18 years old

2. Diagnosis of Ph-positive (by cytogenetics) or BCR-ABL-positive (by PCR) CP-CML

3. 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

• 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

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

Exclusion Criteria:

1. Any 1st line anti-CML treatment other than TKI (apart from therapy with hydroxyurea)

2. 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)

3. Concurrent participation in any other clinical trial involving another investigational drug within 4 weeks prior to enrollment and throughout participation in PONS-Study

4. New York Heart Association (NYHA) cardiac class 3-4 heart disease

5. Cardiac Symptoms within the past 12 months prior recruitment