Safety and Efficacy of Ponatinib Followed by Imatinib in Patients With Chronic Myelogenous Leukemia in Chronic Phase

NCT04070443 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: ET18000120 (TIPI)
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 28

Brief Summary

The investigators hypothesize that, in newly diagnosed de novo chronic phase CML patients, an induction treatment with ponatinib for 6 months should increase the rate of patients reaching a stable MR4.5 allowing cessation of imatinib treatment. The investigators proposal is to conduct a multicenter, Phase II trial to evaluate the safety, clinical and biological activity of an induction treatment with ponatinib for 6 months, followed by a consolidation treatment with imatinib in newly diagnosed de novo chronic phase CML patients.

Conditions

Philadelphia Chromosome Positive CML; BCR-ABL Positive Chronic Myelogenous Leukemia

Keywords

Clinical Trial, Phase II; Tyrosine Kinase Inhibitors; Induction phase; Consolidation phase

Outcome Measures

Primary Outcomes (1)

• Impact of Ponatinib induction treatment on the TFR rate

  Rate of patients reaching a stable MR4.5 (BCR-ABL (IS) ≤0.0032% with at least 32,000 copies of ABL) for ≥ 2 years from Month 36 after initiation of ponatinib.

  36 months after initiation of ponatinib

Secondary Outcomes (18)

• Clinical activity of the proposed therapeutic strategy

  up to 24 months after ponatinib initiation

• Clinical activity of the proposed therapeutic strategy

  up to 6 months after ponatinib initiation

• Clinical activity of the proposed therapeutic strategy

  from the first intake of Ponatinib until one of this criteria is reached, assessed up to 5 years

• Clinical activity of the proposed therapeutic strategy

  from the first intake of Ponatinib until one of this criteria is reached, assessed up to 5 years

• Clinical activity of the proposed therapeutic strategy

  from the date of inclusion until the date of the first progression or date of death from any cause, whichever came first, assessed up to 5 years

Study Arms (1)

Induction phase with Ponatinib followed by Imatinib

EXPERIMENTAL

Ponatinib (Iclusig®) : Tyrosine Kinase Inhibitor (BCR-ABL); oral (tablets) : 30mg/day during 6 months (induction phase); Takeda \& Incyte Biosciences. Imatinib (either Glivec® or any generic form) : Tyrosine Kinase Inhibitor (BCR-ABL, ABL, KIT and PDGFRA receptor tyrosine kinases); oral : 400 mg/day during at least 30 months (then, depending of MR4.5)

Drug: Ponatinib; Drug: Imatinib

Interventions

Ponatinib DRUG

30mg/day; 6 months. Dose adaptation procedures are planned in case of toxicity.

Induction phase with Ponatinib followed by Imatinib

Imatinib DRUG

400 mg/day; at least 30 months (M7 to M36), then depending of MR4.5 . Dose adaptation procedures are planned in case of toxicity.

Induction phase with Ponatinib followed by Imatinib

Eligibility Criteria

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

You may qualify if:

• Male or female patients aged ≥18 and ≤65 years at time of inform consent signature.
• Cytologically confirmed CML, Philadelphia chromosome positive with or without additional chromosomal abnormalities and/or BCR-ABL positive (Major BCR (M-BCR) transcript exclusively), i. e. Cryptic Philadelphia chromosome patients can be enrolled:
• diagnosed within the past 3 months prior to D1 (i.e. within 60 days \[± 7 days\] since the date of first cytogenetic analysis),
• in chronic phase defined by i) \<15 % blasts in peripheral blood and bone marrow, ii) \< 30% blast plus promyelocytes in peripheral blood and bone marrow; iii) \< 20 % basophils in peripheral blood and iv) ≥100 X 109 platelets/L in peripheral blood,
• no extra-medullary disease.
• All EUTOS long-term survival Scores.
• No prior treatment for CML with any tyrosine kinase inhibitor (eg. imatinib, dasatinib, nilotinib or bosutinib), or busulphan; interferon-alpha; homoharringtonine; cytosine arabinoside; or any other investigational agent; with the exception of hydroxyurea and/or anagrelide which are the only authorized prior treatments.
• Note: Hydroxyurea should be stopped at least 24 hours prior the initiation of ponatinib.
• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0, 1 or 2.
• Adequate organ functions as defined below according to lab tests performed within 7 days before Day 1:
• Renal function:
• \- Serum creatinine clearance ≥ 50 mL/min/1.73m2 according to CKD-EPDI formula or serum creatinine ≤ 2 upper limit of normal (ULN).
• Hepatic function:
• Serum bilirubin \< 1.5 × ULN, with the following exception: Patients with known Gilbert disease who have serum bilirubin level ≤ 3 ULN may be enrolled.
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase ≤ 2.5 ULN.

You may not qualify if:

• Any form of prior auto- or allo-hemopoietic stem cell transplant.
• Hypersensitivity to the active substance or to any of the excipients of ponatinib and imatinib (see respective IB/SmPC).
• Inability to take oral medication including malabsorption syndrome or other illness that could affect oral absorption of the study treatments (hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption).
• Patients using, or requiring to use while on the study of any not permitted concomitant medications:
• Any approved anti-cancer systemic treatment including chemotherapy, targeted therapy, immunotherapy or any biological therapy,
• Any investigational agents,
• Any treatment able to induce " torsades de pointes ",
• Any strong inducers and inhibitors of CYP3A4.
• Patients with a malignancy other than CP-CML within 5 years prior to Day 1 with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated in situ carcinoma of the cervix, basal or squamous cell skin cancer, localised prostate cancer or ductal in situ carcinoma treated surgically with curative intent).
• Patients with active B or C hepatitis infection. Notes: Patients with past Hepatitis B Virus (HBV) infection or resolved HBV infection (defined as having a negative hepatitis B surface antigen (HBsAg) test and a positive hepatitis B core antibody (HBcAb) test) are eligible.
• Patients with a positive HBcAb test must have a negative HBV DNA test at screening.
• Patients positive for Hepatitis C Virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
• Patients with significant cardiovascular disease, such as New York Heart Association cardiac disease Class II or greater, myocardial infarction within 3 months prior to D1, unstable arrhythmias, unstable angina, peripheral arterial occlusive disease, venous thromboembolism or pulmonary embolism, brain stroke, evolutive ischemic cardiopathy; prolonged corrected QT interval (QTc) interval on baseline electrocardiogram (\>450 msec on the Fridericia's correction) despite correction of predisposants factors; long congenital QT syndrome.
• Any of the following medical conditions despite adequate therapeutic management:
• Uncontrolled HTA despite adequate ongoing treatment.

Sponsors & Collaborators

• Centre Leon Berard: lead

Study Sites (28)

Chu Amiens Picardie

Amiens, 80000, France

Location

CHU d'Angers

Angers, France

Location

Centre Hospitalier Annecy-Genevois

Annecy, 74000, France

Location

CH d'Avignon

Avignon, 84000, France

Location

Chru Besançon

Besançon, 25000, France

Location

Institut Bergonie

Bordeaux, 33000, France

Location

Chru Brest

Brest, France

Location

Institut D'Hematologie de Basse Normandie

Caen, 14000, France

Location

Chu D'Estaing

Clermont-Ferrand, 63000, France

Location

Centre Hospitalier Sud Francilien

Corbeil-Essonnes, 91000, France

Location

Hopital Henri Mondor

Créteil, 94000, France

Location

CHU de Grenoble

Grenoble, 38000, France

Location

CH de Versailles - Hôpital André Mignot

Le Chesnay, France

Location

Hôpital Claude Huriez - CHRU de Lille

Lille, France

Location

CHU Limoges - Hôpital Dupuytren

Limoges, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

Institut Paoli Calmettes

Marseille, 13000, France

Location

Hopital Saint Eloi

Montpellier, 34000, France

Location

Chu Hotel Dieu

Nantes, 44000, France

Location

CHU Nîmes Caremeau - Institut de Cancérologie du Gard

Nîmes, France

Location

Hopital Saintantoine

Paris, 75000, France

Location

Chu Poitiers

Poitiers, France

Location

Chu - Hopital de Pontchaillou

Rennes, 35000, France

Location

Institut de Cancérologie Lucien Neuwirth

Saint-Priest-en-Jarez, France

Location

CHU Strasbourg

Strasbourg, 67000, France

Location

Iuct Toulouse - Oncopole

Toulouse, France

Location

CHRU Nancy/Brabois

Vandœuvre-lès-Nancy, 54500, France

Location

Hopital Paul Brousse

Villejuif, 94800, France

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

ponatinib; Imatinib Mesylate

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

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Franck-Emmanuel NICOLINI, MD

  Centre Leon Berard

  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: July 19, 2019
• First Posted: August 28, 2019
• Study Start: November 13, 2019
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2029
• Last Updated: November 18, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (28)