Study in Patients With Chronic Leukemia

NCT ID: NCT03807479

Last Updated: 2023-09-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-11
• Study Completion Date: 2023-08-31

Brief 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.

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.

Conditions

Leukemia, Myeloid, Chronic-Phase

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ponatinib

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.

Group Type: EXPERIMENTAL

Ponatinib

Intervention Type: DRUG

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

Interventions

Ponatinib

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

Intervention Type: DRUG

Other Intervention Names

Iclusig

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Incyte Biosciences International Sàrl

INDUSTRY

Sponsor Role: collaborator

GWT-TUD GmbH

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philipp le Coutre, Prof.

Role: PRINCIPAL_INVESTIGATOR

Charité Berlin - Department of Hematology, Oncology and Tumor Immunology

Locations

University Hospital

Halle, Saxony-Anhalt, Germany

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

Aachen, , Germany

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

Berlin, , Germany

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

Essen, , Germany

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

Greifswald, , Germany

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

Hamburg, , Germany

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

Mannheim, , Germany

Clinic for Hematologie

Marburg, , Germany

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

Minden, , Germany

University Hospital Ulm - Department for internal medicine III

Ulm, , Germany

Countries

Germany

Other Identifiers

PONS_11272

Identifier Type: -

Identifier Source: org_study_id