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Consolidation Treatment With Ponatinib 15 mg on Treatment Free-Remission Rate in Patients With Chronic Myeloid Leukemia

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ClinicalTrials.gov Identifier: NCT04043676
Recruitment Status : Recruiting
First Posted : August 2, 2019
Last Update Posted : August 2, 2019
Information provided by (Responsible Party):
Fundación Teófilo Hernando, Spain

Brief Summary:

Ponatinib has shown to induce deeper molecular responses compared with imatinib. Therefore, ponatinib treatment could increase the proportion of patients who could discontinue treatment successfully. This strategy that includes treatment change to a more powerful treatment before treatment discontinuation has not been evaluated in any of the previous clinical trials, and will be explored in the current study.

In this framework, the purpose is to determine the rate of successful treatment-free remission (TFR) within the first 48 weeks following cessation of treatment in patients who achieved Molecular Response 4 (MR4) on imatinib and maintained MR4 on ponatinib after a switch from imatinib. Eligible patients have been previously treated with imatinib as unique tyrosine kinase inhibitor (at least 4 years) and have documented MR4 (at least 12 months) at the time of switch to ponatinib to study entry.

Condition or disease Intervention/treatment Phase
Chronic Myeloid Leukemia Drug: Ponatinib Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: 40 patients of both genders with chronic myeloid leukemia in MR4. Each patient will enter in the ponatinib consolidation phase (48 weeks) and them in the ponatinib treatment-free remission (96 weeks).
Masking: None (Open Label)
Masking Description: This is a single-arm, open label study designed to determine the rate of successful treatment free remission (TFR) in patients who achieved and maintained molecular response 4 (MR4) on ponatinib. This study has 2 main phases: ponatinib consolidation (48 weeks), and ponatinib TFR phases (96 weeks). All patients who have received a minimum of 4 years of imatinib therapy as unique TKI therapy, he/she has documented MR4 at least 12 months for study entry, and he/she shall continue with MR4 before the discontinuation of the ponatinib treatment.
Primary Purpose: Treatment
Official Title: Multicenter, Open-Label, Single Arm, Phase II Exploratory Study to Evaluate the Effect of a One-Year Consolidation Treatment With Ponatinib 15 mg on Treatment Free-Remission Rate in Patients With Philadelphia-Positive Chronic Myeloid Leukemia, Who Had Previously Achieved a Deep Molecular Response With Imatinib
Actual Study Start Date : April 30, 2019
Estimated Primary Completion Date : April 30, 2022
Estimated Study Completion Date : April 30, 2023

Arm Intervention/treatment
Experimental: Ponatinib Treatment
Patients will be treated with 15 mg/day of ponatinib during 48 weeks. If a patient maintains MR4 throughout the 48 weeks, he/she will be eligible to start the ponatinib TFR phase. If a patient has confirmed loss of MR4 (two consecutive BCR-ABL > 0.01% IS) or loss of MMR (no confirmation needed), he/she will not be eligible for the TFR phase. Instead, he/she will restart imatinib treatment.
Drug: Ponatinib
All patient will take 15 mg/day ponatinib oral during 48 weeks.

Primary Outcome Measures :
  1. Loss MR4 [ Time Frame: 96 weeks (48 weeks ponatinib consolidation phase plus 48 weeks ponatinib treatment-free remission) ]
    Proportion of patients without confirmed loss of MR4 or loss of MMR (don't require confirmation) within 48 weeks following ponatinib therapy cessation.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Male or female patients ≥ 18 years of age.
  2. ECOG performance status of 0, 1, or 2.
  3. Patient with diagnosis of BCR-ABL positive CML-CP.
  4. Patient has received a minimum of 4 years of imatinib treatment, as unique TKI therapy.
  5. Patient has achieved MR4 during at least 12 months with imatinib treatment, and determined by PCR lab assessment at screening.
  6. Adequate end organ function.
  7. Patients must have the following electrolyte values ≥ LLN limits or corrected to within normal limits with supplements prior to the first dose of study medication: Potassium, Magnesium, Total calcium (corrected for serum albumin).
  8. Patients must have normal marrow function
  9. Patients with preexisting, well-controlled, diabetes are not excluded.
  10. Have normal QTcF interval on screening ECG evaluation, defined as QTcF of ≤ 450 ms in males or ≤ 470 ms in females.
  11. Have a negative pregnancy test documented prior to enrollment
  12. Be willing and able to comply with scheduled visits and study procedures.
  13. Written informed consent obtained prior to any screening procedures.

Exclusion Criteria:

  1. Prior AP, BC or autologous or allogenic transplant.
  2. Patients with known atypical transcript.
  3. CML treatment resistant mutation(s).
  4. Are taking medications with a known risk of torsades de pointes (Appendix A)
  5. Patient ever attempted to permanently discontinue imatinib or ponatinib treatment.
  6. Severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks.
  7. Have clinically significant, uncontrolled, or active cardiovascular disease.
  8. Have uncontrolled hypertension (diastolic blood pressure > 90 mmHg; systolic > 150 mmHg).
  9. Have a history of alcohol abuse.
  10. History of acute pancreatitis within 1 year prior to study entry or past medical history of chronic pancreatitis.
  11. Have malabsorption syndrome or other gastrointestinal illness that could affect oral absorption of study drug.
  12. Known presence of a significant congenital or acquired bleeding disorder unrelated to cancer.
  13. Have a history of another malignancy; the exception is if patients have been disease-free for at least 5 years.
  14. Have undergone surgery within 14 days prior to first dose of ponatinib.
  15. Treatment with other investigational within 4 weeks of Day 1.
  16. Patients actively receiving therapy with strong CYP3A4 inhibitors and/or inducers.
  17. Patients actively receiving therapy with herbal medicines that are strong CYP3A4 inhibitors and/or inducers.
  18. Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval.
  19. Have an ongoing or active infection.
  20. Have a known history of human immunodeficiency virus infection.
  21. Have hypersensitivity to the ponatinib active substance or to any of its inactive ingredients.
  22. Pregnant or nursing (lactating) women.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04043676

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Contact: Begonya Maestro, PhD (0034) 911923700 ponazero@ifth.es
Contact: Rocio Prieto, PhD (0034) 911923700 ponazero@ifth.es

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Hospital Trials i Pujol Recruiting
Badalona, Barcelona, Spain, 08916
Contact: Blanca Xicoy, Dr.         
Hospital Vall D'Hebron Recruiting
Barcelona, Spain, 08035
Contact: Guillermo Orti, Dr.         
Hospital Universitario de Gran Canarias Dr. Negrin Recruiting
Las Palmas De Gran Canaria, Spain, 35010
Contact: Maria Teresa Gomez, Dr.         
Hospital Unversitario de la Princesa Recruiting
Madrid, Spain, 28006
Contact: Juan Luis Steegmann, MD PhD       jlsteegmann@gmail.com   
Hospital Universitario Ramon y Cajal Recruiting
Madrid, Spain, 28034
Contact: Valentin Garcia Gutierrez, MD PhD       jvalentingg@gmail.com   
Hospital Universitario Doce de Octubre Recruiting
Madrid, Spain, 28041
Contact: Rosa Ayala, MD PhD         
Hospital Regional de Malaga Recruiting
Málaga, Spain, 29010
Contact: Antonio Jimenez, Dr.         
Hospital Universitario de Salamanca Recruiting
Salamanca, Spain, 37007
Contact: Fermin Sanchez-Guija, MD PhD         
Hospital Clinico Universitario de Valencia Recruiting
Valencia, Spain, 46010
Contact: Juan Carlos Hernandez Boluda, Dr.         
Sponsors and Collaborators
Fundación Teófilo Hernando, Spain
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Principal Investigator: Juan Luis Steegmann, MD PhD Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
Principal Investigator: Valentin Garcia Gutierrez, MD PhD Hospital Universitario Ramon y Cajal
Principal Investigator: Rosa Ayala, MD PhD Hospital Universitario Doce de Octubre
Principal Investigator: Luis Felipe Casado, Dr. Hospital Universitario Virgen del Rocio
Principal Investigator: Fermin Sanchez-Guijo, MD PhD University of Salamanca
Principal Investigator: Juan Carlos Hernandez, Dr. Hospital Clínico Universitario de Valencia
Principal Investigator: Guillermo Orti, Dr. Hospital Vall d'Hebron
Principal Investigator: Blanca Xicoy, Dr. Hospital German Trials i Pujol
Principal Investigator: Antonio Jimenez, Dr. Hospital Regional Universitario de Malaga
Principal Investigator: Maria Teresa Gomez, Dr. Hospital Universitario de Gran Canarias Dr. Negrin
Publications of Results:

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Responsible Party: Fundación Teófilo Hernando, Spain
ClinicalTrials.gov Identifier: NCT04043676    
Other Study ID Numbers: PonaZero_study
2017-004565-27 ( EudraCT Number )
First Posted: August 2, 2019    Key Record Dates
Last Update Posted: August 2, 2019
Last Verified: August 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Fundación Teófilo Hernando, Spain:
BCR-ABL positive
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action