Study in Patients With Chronic Leukemia

NCT03807479 | Terminated Phase 2

• 1 other identifier: PONS_11272
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 10

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.

Conditions

Leukemia, Myeloid, Chronic-Phase

Keywords

CP-CML; CML in chronic phase; Chronic Myelogenous Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Outcome Measures

Primary Outcomes (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.

  by 12 moths

Secondary Outcomes (6)

• Time to toxicity

  up to 24 months

• Time to response

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

• Durations of response

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

• Occurrence of BCR-ABL-mutations

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

• Time to progression

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

Study Arms (1)

Ponatinib

EXPERIMENTAL

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

Interventions

Ponatinib DRUG

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

Also known as: Iclusig

Ponatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GWT-TUD GmbH: lead
• Incyte Biosciences International Sàrl: collaborator

Study Sites (10)

University Hospital

Halle, Saxony-Anhalt, 06097, Germany

Location

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

Aachen, 52074, Germany

Location

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

Berlin, 13353, Germany

Location

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

Essen, 45122, Germany

Location

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

Greifswald, 17475, Germany

Location

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

Hamburg, 20099, Germany

Location

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

Mannheim, 68167, Germany

Location

Clinic for Hematologie

Marburg, 35043, Germany

Location

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

Minden, 32429, Germany

Location

University Hospital Ulm - Department for internal medicine III

Ulm, 89081, Germany

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Chronic-Phase; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

ponatinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Philipp le Coutre, Prof.

  Charité Berlin - Department of Hematology, Oncology and Tumor Immunology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2018
• First Posted: January 17, 2019
• Study Start: December 11, 2018
• Primary Completion: February 28, 2023
• Study Completion: August 31, 2023
• Last Updated: September 14, 2023

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (10)