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Leukemia, Myeloid, AcutePhase 2PONALLONCT03690115

Study of Ponatinib (Iclusig) for Prevention of Relapse After Allogeneic Stem Cell Transplantation (allo-SCT) in FLT3-ITD AML Patients

A Phase 2 study testing Ponatinib 30 MG in people with Leukemia, Myeloid, Acute, run by Versailles Hospital at 14 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Recent advances in acute myeloid leukemia (AML) have been characterized by a better understanding of disease biology. As such, FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) have been recognized as conferring a poor prognosis. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Leukemia, Myeloid, Acute
What is being tested?
Ponatinib 30 MG
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
14 sitesFrance
Study dates
2 Dec 2019to 31 Dec 2024
Phase
Phase 2
Are there results?
None posted in the registry

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 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Engraftment
  • Controlled GVHD
  • Positive FLT-3 ITD AML in cytologic complete remission
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status < 2
  • Have adequate renal function: Serum creatinine ≤ 1.5 × upper limit of normal (ULN) for institution
  • Have adequate hepatic function: Total serum bilirubin ≤ 1.5 × ULN, unless due to Gilbert's syndrome; Alanine aminotransferase (ALT) ≤ 2.5 × ULN, or ≤ 5 × ULN if leukemic infiltration of the liver is present ; Aspartate aminotransferase (AST) ≤ 2.5 × ULN, or ≤ 5 × ULN if leukemic infiltration of the liver is present
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  • Have normal pancreatic status: Serum lipase and amylase ≤ 1.5 × ULN
  • Have normal QTcF interval on screening electrocardiogram (ECG) evaluation,defined as QTcF of ≤ 450 ms in males or ≤ 470 ms in females.
  • Platelets ≥ 100 Giga/l; Neutrophils ≥ 1 Giga/l
  • Have a negative pregnancy test documented prior to enrollment (for females of childbearing potential).
  • Agree to use an effective form of contraception with sexual partners throughout study participation (for female and male patients who are fertile).
  • Provide written informed consent.
  • Be willing and able to comply with scheduled visits and study procedures.

Who cannot join

  • HIV positive, active Hepatitis B or C
  • Childbearing or childbreast feeding women
  • Women or men without effective contraceptive barrier if needed
  • Previous myocardial infarction, or cerebral vascular accident, pancreatitis
  • Respiratory insufficiency defined as DLCO <40% of the corrected value
  • Creatinine clearance ≤ 50ml/min
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  • Contra-indication to ponatinib
  • Previous or concurrent second malignancy except for adequately treated basal cell carcinoma of the skin, curatively treated in situ carcinoma of the cervix, curatively treated solid cancer, with no evidence of disease for at least 2 years
  • Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
  • Patients at high or very high risk of cardiovascular disease with any of the following
  • Established cardiovascular disease Cardiac disease:
  • Congestive heart failure greater than class II NYHA or
  • Left ventricular ejection fraction (LVEF) < 50% or
  • Unstable angina (anginal symptoms at rest) or
  • New onset angina (began within the last 3 months) or
  • Myocardial infarction, coronary/peripheral artery disease, congestive heart failure, cerebrovascular accident including transient ischemic attack within the past 12 months or
  • History of thrombolic or embolic events Arrhythmias
  • Any history of clinically significant cardiac arrhythmias requiring anti-arrhythmic therapy.
  • Diabetes Mellitus,
  • Arterial Hypertension,
  • Uncontrolled hypertension defined as systolic blood pressure greater than 140 mmHg or diastolic pressure greater than 90 mmHg, despite optimal medical management and optimal measurement (http://www.has-sante.fr/portail/display.jsp?id=c_272459)
  • Any history of hypertension with
  • Hypertensive encephalopathy
  • Posterior leucoencephalopathy
  • Aortic or artery dissection
  • Familial dysplipidemia.
  • Taking medications that are known to be associated with Torsades de Pointes (see

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

France14 sites

  • CHU Angers

    Angers

  • CHu Brest

    Brest

  • CHU Caen

    Caen

  • CHU Clermont Ferrand

    Clermont-Ferrand

  • CHU Grenoble

    Grenoble

  • CHU Lille

    Lille

  • CHU Limoges

    Limoges

  • Chevallier

    Nantes

  • Hopital St Antoine

    Paris

  • Hopital St Louis

    Paris

  • CHu Lyon

    Pierre-Bénite

  • CHU Poitiers

    Poitiers

  • CRLC Toulouse

    Toulouse

  • CHU Nancy

    Vandœuvre-lès-Nancy

Other trials in France

About this study

Official title: Phase 2 Study of Ponatinib (Iclusig) for Prevention of Relapse After Allogeneic Stem Cell Transplantation (allo-SCT) in FLT3-ITD AML Patients: the PONALLO Trial."

Recent advances in acute myeloid leukemia (AML) have been characterized by a better understanding of disease biology. As such, FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) have been recognized as conferring a poor prognosis. The FLT3-ITD molecular mutation is observed in about one-quarter of patients diagnosed with AML. Patients presenting with this abnormality are referred for early allogeneic stem-cell transplantation (allo-SCT). However, some data suggest that FLT3-ITD remains associated with a poor prognosis even after allo-SCT because of higher risk of relapse and strategies for preventing relapse in the post-transplant setting are required (Hu et al, Expert Rev Hematol, 2014). For example, in a large cohort of patients (Brunet et al, JCO, 2012), the incidence of relapse for FLT3-ITD AML patients after allo-SCT was 30% at 2-years, significantly higher compared to FLT3-ITD negative patients (p=0.006).

Ponatinib (Iclusig®) is an orally available, tyrosine kinase inhibitor with a unique binding mechanism allowing inhibition of BCR-ABL kinases, including those with the T315I point mutation. Ponatinib also has in vitro inhibitory activity against a discrete set of kinases implicated in the pathogenesis of other hematologic malignancies, including FLT3, KIT, fibroblast growth factor receptor 1 (FGFR1), and platelet derived growth factor receptor α (PDGFRα). In vitro activity of ponatinib in AML has been already demonstrated (Gozgit et al, Mol Cancer Ther, 2011; Smith et al, Blood 2013). If some trials are on-going to test ponatinib alone or in combination with chemotherapy in FLT3-ITD AML (Clinical.trials.gov), no study is dedicated to the use of ponatinib in the post-transplant setting in order to prevent relapse in these patients.

The main goal of this study will be to determine the maximal tolerated dose (MDT) of ponatinib after allo-SCT in FLT3-ITD AML patients, then to investigate the efficacy of ponatinib in a larger cohort of patients

Being tested
Ponatinib 30 MG
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

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

  • Ponatinib 30 MGDrug

    Administration of ponatinib after allo-SCT transplant in FLT3-ITD AML patient

Study groups in NCT03690115
Study groupRoleWhat they receive
ExperimentalExperimentalAdministration of ponatinib after allo-SCT transplant in FLT3-ITD AML patient
Receives: Drug: Ponatinib 30 MG

What is being measured

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

  1. Relapse incidence at 2 years from transplant

    Measured: 2 years

Secondary outcomes (7)

  1. Overall survival

    time interval from the graft (day 0) until the date of last follow-up or death

    Measured: 2 years

  2. Leukemia free survival

    time interval from the date of the graft (day 0) until the date of last follow-up, death or relapse

    Measured: 2 years

  3. Non-relapse mortality (NRM)

    incidence of mortality due to all causes except relapse after transplant, considering that cause of death for patients having relapsed but dying from another cause is relapse

    Measured: day 100

  4. Acute and chronic GVHD

    NIH score

    Measured: 2 years

  5. Influence of Ponatinib on Immune reconstitution PB lymphocyte cells

    an immunophenotype of PB lymphocytes will be performed by flow cytometry at +3, +6, +9 and +12 months post-transplant to study the reconstitutions of CD3, CD4 and CD8 T cells, B and NK cells. The results will be expressed as absolute counts (Giga/L). We want to establish the potential influence of ponatinib on the reconstitution of these cells

    Measured: 1 years

  6. Inflence of Ponatinib on Chimerism of Donor peripheral blood and CD3 T cells

    Donor peripheral blood and CD3 T cells chimerism will be studied using molecular markers and RT-PCR at day +30, +60, +90, and +6, +12 months post-transplant. We want to establish the potential influence of ponatinib on the chimerism post-transplant.

    Measured: 1 years

  7. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    Measured: 2 years

Timeline

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

  1. First posted1 Oct 2018
  2. Study start2 Dec 2019
  3. Primary completion5 Dec 2023
  4. Study completion31 Dec 2024

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
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03690115
Sponsor's protocol ID
P1701_ PONALLO
Acronym
PONALLO
Status last verified
Mar 2025
First submitted
4 Apr 2018
Last updated
25 Mar 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ponatinib 30 MG in people with Leukemia, Myeloid, Acute, run by Versailles Hospital at 14 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 13 inclusion and 27 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: finished, as of the sponsor's last update on 25 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Relapse incidence at 2 years from transplant (time frame: 2 years). 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 NCT03690115.

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 25 Mar 2025.

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