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Philadelphia Chromosome Positive CMLPhase 2TIPINCT04070443

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

A Phase 2 study testing Ponatinib and Imatinib in people with Philadelphia Chromosome Positive CML and BCR-ABL Positive Chronic Myelogenous Leukemia, run by Centre Leon Berard at 28 sites in France.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
Ponatinib and Imatinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
170 participants
Where
28 sitesFrance
Study dates
13 Nov 2019to 1 Jun 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • Amylase or Lipase ≤ 1.5 × ULN Total cholesterol ≤1.5 ULN
  • Women of child-bearing potential must have a negative serum pregnancy test within 7 days before study drug start and must agree to use an effective form of contraception from the time of the negative pregnancy test up to 3 months after the last dose of study treatments.
  • Fertile men must agree to use an effective method of contraception during the study and for up to 3 months after the last dose of study treatments.
  • Patient should understand, sign, and date the written voluntary informed consent form prior to any protocol-specific procedures performed. Patient should be able and willing to comply with study visits and procedures as per protocol.
  • Patients must be covered by a medical insurance.

Who cannot join

  • 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,
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  • 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.
  • Diabetes with documented target organ damage.
  • Pregnant or lactating women.

Trial locations and contacts

28 sites in 1 country.

28 sites in 1 country

France28 sites

  • Chu Amiens Picardie

    Amiens, 80000

  • CHU d'Angers

    Angers

  • Centre Hospitalier Annecy-Genevois

    Annecy, 74000

  • CH d'Avignon

    Avignon, 84000

  • Chru Besançon

    Besançon, 25000

  • Institut Bergonie

    Bordeaux, 33000

  • Chru Brest

    Brest

  • Institut D'Hematologie de Basse Normandie

    Caen, 14000

  • Chu D'Estaing

    Clermont-Ferrand, 63000

  • Centre Hospitalier Sud Francilien

    Corbeil-Essonnes, 91000

  • Hopital Henri Mondor

    Créteil, 94000

  • CHU de Grenoble

    Grenoble, 38000

  • CH de Versailles - Hôpital André Mignot

    Le Chesnay

  • Hôpital Claude Huriez - CHRU de Lille

    Lille

  • CHU Limoges - Hôpital Dupuytren

    Limoges

  • Centre Léon Bérard

    Lyon, 69008

  • Institut Paoli Calmettes

    Marseille, 13000

  • Hopital Saint Eloi

    Montpellier, 34000

  • Chu Hotel Dieu

    Nantes, 44000

  • CHU Nîmes Caremeau - Institut de Cancérologie du Gard

    Nîmes

  • Hopital Saintantoine

    Paris, 75000

  • Chu Poitiers

    Poitiers

  • Chu - Hopital de Pontchaillou

    Rennes, 35000

  • Institut de Cancérologie Lucien Neuwirth

    Saint-Priest-en-Jarez

  • CHU Strasbourg

    Strasbourg, 67000

  • Iuct Toulouse - Oncopole

    Toulouse

  • CHRU Nancy/Brabois

    Vandœuvre-lès-Nancy, 54500

  • Hopital Paul Brousse

    Villejuif, 94800

Other trials in France

About this study

Official title: A Multicentre, Open-label Phase II Trial Evaluating the Safety and Efficacy of Ponatinib Induction Followed by Imatinib Maintenance in Adult Patients With Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) ≤ 65 Years

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.

Read the detailed description

TREATMENT PLAN :

All eligible patients will be treated:

  • During the induction Phase (Month 1 to Month 6) with ponatinib (30mg/day) single agent; then
  • During the consolidation Phase (Month 7 to Month 36) with imatinib (400mg/day) single agent; then
  • From M36 :
  • Patients with stable MR4.5 (i.e. since at least 2 years) will enter in the TFR phase and will stop imatinib treatment. Thereafter, in case of MMR loss, imatinib will be re-introduced as per investigator judgement (including for dose).
  • Patients without stable MR4.5 will continue imatinib treatment until stable MR4.5, or M60, PD, death, withdrawal of consent or overall trial completion. Such patients will be allowed to enter into the TFR phase as soon as a stable 2-year MR4.5 is reached: however, they will be considered as a failure for the primary endpoint analysis.

STATISTICS :

A total of 170 patients will be enrolled in this study.

According to a Fleming design, with a P0=20% as minimal efficacy rate and P1=30% as an expected target, 156 patients should be enrolled, assuming an unilateral type I error alpha of 5% and 90% power. At the time of analysis, if at least 40 successes are observed among the 156 evaluable patients, the treatment will be considered as interesting for further investigation in this indication. Considering that some patients may withdraw their consent before 36 months (about 10%), the investigators plan to enrol 170 patients in total.

DATA ENTRY, DATA MANAGEMENT AND STUDY MONITORING All the data concerning the patients will be recorded in the electronic case report form (eCRF) throughout the study. Serious adverse event (SAE) and Adverse Event of Specific Interest (AESI) reporting will be also paper-based by e-mail and/or Fax.

The sponsor will perform the study monitoring and will help the investigators to conduct the study in compliance with the clinical trial protocol, Good Clinical Practices (GCP) and local law requirements.

Being tested
Ponatinib, Imatinib
Keywords
Clinical Trial, Phase II, Tyrosine Kinase Inhibitors, Induction phase, Consolidation phase
Medical subject headings
Leukemia, Myelogenous, Chronic, BCR-ABL Positive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PonatinibDrug

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

  • ImatinibDrug

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

Study groups in NCT04070443
Study groupRoleWhat they receive
Induction phase with Ponatinib followed by ImatinibExperimentalPonatinib (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)
Receives: Drug: Ponatinib; Drug: Imatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 36 months after initiation of ponatinib

Secondary outcomes (18)

  1. Clinical activity of the proposed therapeutic strategy

    For all patients : Rate of patients with MR4.5; MR4.0 and MMR at 1, 2, 3, 6, 9, 12, 24 months after ponatinib initiation

    Measured: up to 24 months after ponatinib initiation

  2. Clinical activity of the proposed therapeutic strategy

    For all patients : Rate of patients with a BCR-ABL/ABL (IS) ≤ 10% and rate of patients with CCyR (or its molecular equivalent, BCR-ABL/ABL (IS) ≤ 10%) at 3 and 6 months after ponatinib initiation.

    Measured: up to 6 months after ponatinib initiation

  3. Clinical activity of the proposed therapeutic strategy

    For all patients : Time to MR4.5, MR4.0 or MMR following ponatinib initiation

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

  4. Clinical activity of the proposed therapeutic strategy

    For all patients : Duration of MR4.5, MR4.0 or MMR

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

  5. Clinical activity of the proposed therapeutic strategy

    For all patients : Progression Free survival

    Measured: 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

  6. Clinical activity of the proposed therapeutic strategy

    For all patients : Overall survival

    Measured: From the date of inclusion until the date of death from any cause, whichever came first, assessed up to 5 years

  7. Clinical activity of the proposed therapeutic strategy

    For patients reaching TFR criteria and following imatinib cessation: Rate of successful TFR (patients sill with MR4.5) at 3, 6, 9, 12 and 24 months after imatinib cessation

    Measured: 3, 6, 9, 12 and 24 months after imatinib cessation

  8. Clinical activity of the proposed therapeutic strategy

    For patients reaching TFR criteria and following imatinib cessation: Duration of TFR after imatinib cessation.

    Measured: from imatinib cessation until the date of progression/relapse, whichever came first, assessed up to 5 years

  9. Clinical activity of the proposed therapeutic strategy

    For patients reaching TFR criteria and following imatinib cessation: OS after imatinib cessation

    Measured: From the date of imatinib cessation until the date of death from any cause, assessed up to 5 years

  10. Clinical activity of the proposed therapeutic strategy

    For patients reaching TFR criteria and following imatinib cessation: PFS after imatinib cessation

    Measured: from the date of imatinib cessation until the date of the first progression or date of death from any cause, whichever came first, assessed up to 5 years

  11. Clinical activity of the proposed therapeutic strategy

    For patients reaching TFR criteria and following imatinib cessation: Event-free survival according ELN recommendations

    Measured: from the date of ponatinib initiation until the onset of the following events: loss of responses, accelerated phase or blast crisis at any time, death at any time from any cause; drug discontinuation due to adverse events, assessed up to 5 years

  12. Clinical activity of the proposed therapeutic strategy

    For patients reaching TFR criteria and following imatinib cessation: Rate of TKI-withdrawal syndrome after Imatinib cessation

    Measured: from the date of imatinib cessation until 30 days after the last study drugs intake or until initiation of a new anti-cancer treatment, whichever came first, assessed up to 5 years

  13. Clinical activity of the proposed therapeutic strategy

    For patients reaching TFR criteria and following imatinib cessation: Rate of MMR, MR4.0 and MR4.5 recovery in case of imatinib re-introduction (

    Measured: from the date of imatinib re introduction until date of MMR or MR4.5, assessed up to 5 years

  14. Incidence of Adverse Events of the proposed therapeutic strategy

    • Hematologic and non-hematologic AEs graded according to the NCI CTCAE v5.0
    • Incidence of arterial thrombotic events during the induction phase and during the consolidation phase.

    Measured: from the signature of the ICF and the first intake of study drug until 30 days after the last study drugs intake or until initiation of a new anti-cancer treatment, assessed up to 5 years

  15. Quality of Life (QLQ-CML24 questionnaire)

    Evolution of Quality of life according to QLQ-CML24 questionnaire.

    Measured: At screening, at each visit from Month 1 to Month 60 (if applicable) and then during the TFR phase and at STSV 30 days, assessed up to 5 years

  16. Quality of Life (QLQ-C30 questionnaire)

    Evolution of Quality of life according to QLQ-C30 questionnaire.

    Measured: At screening, at each visit from Month 1 to Month 60 (if applicable) and then during the TFR phase and at STSV 30 days, assessed up to 5 years

  17. Ponatinib pharmacokinetics (non-decisional)

    Plasma concentrations of ponatinib over the 6 months of the induction period.

    Measured: At screening, at each visit from Month 6 (induction phase)

  18. Patient' compliance to the proposed therapeutic strategy

    Compliance to ponatinib and imatinib as evaluated using the Morisky medication adherence scale questionnaire

    Measured: At each visit during induction and consolidation phase

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Aug 2019
  2. Study start13 Nov 2019
  3. Primary completion1 Jun 2029 (estimated)
  4. Study completion1 Jun 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
170 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04070443
Sponsor's protocol ID
ET18000120 (TIPI)
Acronym
TIPI
Status last verified
Nov 2025
First submitted
19 Jul 2019
Last updated
18 Nov 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ponatinib and Imatinib in people with Philadelphia Chromosome Positive CML and BCR-ABL Positive Chronic Myelogenous Leukemia, run by Centre Leon Berard at 28 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 18 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Impact of Ponatinib induction treatment on the TFR rate (time frame: 36 months after initiation of ponatinib). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04070443.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2025; AzTrials last refreshed its copy on 8 Nov 2026.

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