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Philadelphia-Positive ALLPhase 2NCT04475731

Ponatinib in Adult Ph+ ALL Patients With MRD Positivity or Hematological Relapse

A Phase 2 study testing Ponatinib in people with Philadelphia-Positive ALL and Acute Lymphoblastic Leukemia, in Relapse, run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 22 sites in Italy.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This is a phase II interventional trial to evaluate if the use of ponatinib, with or without chemotherapy, can induce a molecular remission in MRD-positive patients, in patients in hematologic and extra-hematologic relapse and in the few patients who never achieved an hematologic remission after whatever prior… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ponatinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
67 participants
Where
22 sitesItaly
Study dates
4 May 2021to Nov 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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Ph+ ALL patients with evidence of MRD disease or in hematologic and extra-hematologic relapse/refractoriness after any previous treatment, will be considered eligible to enter the study.
  • Age ≥18 years old with no upper age limit.
  • Adequate hepatic function as defined by the following criteria:
  • total serum bilirubin ≤1.5 x upper limit of normal (ULN), unless due to Gilbert's syndrome
  • alanine aminotransferase (ALT) ≤2.5 × ULN
  • aspartate aminotransferase (AST) ≤2.5 × ULN.
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  • Adequate pancreatic function as defined by the following criterion:
  • serum lipase and amylase ≤1.5 × ULN.
  • For females of childbearing potential, a negative pregnancy test must be documented prior to enrollment.
  • Female and male patients who are fertile must agree to use an effective form of contraception with their sexual partners from enrollment through 4 months after the end of treatment.
  • Signed written informed consent according to ICH/EU/GCP and national local laws.

Who cannot join

  • WHO performance status ≤ 50% (Karnofsky) or ≥ 3 (ECOG).
  • Uncontrolled active HBV or HCV hepatitis, or AST/ALT ≥ 2.5 x ULN and bilirubine ≥ 1.5 x ULN not due to the disease.
  • History of acute pancreatitis within 1 year of study or history of chronic pancreatitis.
  • History of alcohol abuse.
  • Ongoing or active uncontrolled infections.
  • Uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL).
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  • Clinically significant, uncontrolled or active cardiovascular disease, specifically including, but not restricted to:
  • any history of myocardial infarction, stroke, or revascularization
  • unstable angina or transient ischemic attack within 6 months prior to enrollment
  • congestive heart failure within 6 months prior to enrollment, or left ventricular ejection fraction (LVEF) less than lower limit of normal per local institutional standards within 6 months prior to enrollment
  • history of clinically significant (as determined by the treating physician) atrial arrhythmia
  • any history of ventricular arrhythmia
  • any history of venous thromboembolism including deep venous thrombosis or pulmonary embolism
  • uncontrolled hypertension (diastolic blood pressure >90 mm Hg; systolic >140 mm Hg). Patients with hypertension should be under treatment on study entry to effect blood pressure control.
  • Taking medications that are known to be associated with Torsades de Pointes.
  • Taking any medications or herbal supplements that are known to be strong inhibitors of CYP3A4 within at least 14 days before the first dose of ponatinib.
  • Creatinine level >2.5mg/dl or glomerular filtration rate (GFR) <20 ml/min or proteinuria >3.5 g/day.
  • Patients who are currently receiving treatment with any of the medications listed in Appendix E if the medications cannot be either discontinued or switched to a different medication prior to starting study drug. The medications listed in Appendix E have the potential to prolong QT.

Trial locations and contacts

22 sites in 1 country.

22 sites in 1 country

Italy22 sites

  • Aou Ospedali Riuniti "Umberto I - G.M. Lancisi - G. Salesi"- Ancona - Sod Clinica Ematologica

    Ancona

  • Area Vasta N. 5 Ascoli Piceno - S. Benedetto Del Tronto, Presidio Ospedaliero Av5 Osp. Gen. Prov.Le "C.G.Mazzoni" - Uoc Ematologia

    Ascoli Piceno

  • Ao Di Rilievo Nazionale E Di Alta Specialità "San Giuseppe Moscati" - Avellino - Uoc Ematologia Con Unità Di Trapianto

    Avellino

  • Aou Consorziale Policlinico - Bari - Uo Ematologia Con Trapianto

    Bari

  • Asst Papa Giovanni Xxiii - Ospedale Di Bergamo - Sc Ematologia

    Bergamo

  • Aou Di Bologna - Policlinico S. Orsola-Malpighi - Uoc Ematologia

    Bologna

  • Asst Degli Spedali Civili Di Brescia - Uo Ematologia

    Brescia

  • Aso S. Croce E Carle - Cuneo - Sc Ematologia

    Cuneo

  • Aou Careggi - Firenze - Sod Ematologia

    Florence

  • Aou Policlinico "G. Martino" - Messina - Uoc Ematologia

    Messina

  • Aulss 3 Serenissima, Ospedale Dell'Angelo - Mestre - Uo Ematologia

    Mestre

  • Asst Grande Ospedale Metropolitano Niguarda - Milano - Sc Ematologia

    Milan

  • Irccs Ospedale S. Raffaele - Milano - Uo Oncoematologia

    Milan

  • Aou Federico Ii - Napoli - Uoc Ematologia

    Naples

  • Ao Di Perugia, Ospedale S. Maria Della Misericordia - Ematologia E Trapianto Midollo Osseo

    Perugia

  • Ao Ospedali Riuniti Marche Nord - Ospedale San Salvatore - Pesaro - Uoc Ematologia E Centro Trapianti

    Pesaro

  • Università Degli Studi Di Roma "Sapienza" - Dipartimento Di Medicina Traslazionale E Di Precisione - U.O.C. Ematologia

    Roma

  • Aou "San Giovanni Di Dio E Ruggi D'Aragona" - Salerno - Uoc Ematologia E Trapianti Di Cellule Staminali Emopoietiche

    Salerno

  • Ente Ecclesiastico Casa Sollievo Della Sofferenza - San Giovanni Rotondo - Ematologia

    San Giovanni Rotondo

  • Aou Senese - Uoc Ematologia E Trapianti

    Siena

  • Aou Città Della Salute E Della Scienza, Ospedale S. Giovanni Battista Molinette - Torino - Sc Ematologia 2

    Torino

  • Aou Integrata Di Verona, Policlinico G.B. Rossi - Uoc Ematologia

    Verona

Other trials in Italy

About this study

Official title: Ponatinib for the Management of Minimal Residual Disease (MRD) and Hematologic Relapse in Adult Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL) Patients

This is a phase II interventional trial to evaluate if the use of ponatinib, with or without chemotherapy, can induce a molecular remission in MRD-positive patients, in patients in hematologic and extra-hematologic relapse and in the few patients who never achieved an hematologic remission after whatever prior treatment.

Read the detailed description

This is a phase II interventional multicenter study for adult patients with Ph+ALL who:

  • Are MRD+ (i.e. BCR-ABL1/ABL1 >0.01) (or loose their molecular response) after whichever kind of previous treatment. MRD positivity is indeed regarded as a relapse/resistance, since it represents the early recognition of cases who will eventually experience an hematologic recurrence of disease.
  • Are in hematologic relapse after whichever kind of previous treatment.
  • Have never achieved an hematologic remission at least after one month of treatment.

Patients will be treated with Ponatinib at a dose of 45 mg/die per os for 28 days for 3 cycles and - if in hematologic and extra-hematologic relapse/refractoriness, clinically fit and according to medical decision - with concurrent systemic chemotherapy. In case of CMR achievement, dosing will be reduced to 30 mg. In case of toxicity, Ponatinib will be reduced to 30 (or 15) mg daily.

Being tested
Ponatinib
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

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

  • PonatinibDrug

    Ponatinib 45 mg/day x 4 weeks x 3 courses.

    +/- chemotherapy:

    • vincristine or
    • L-VAMP (leucovorin, vincristine, aracytin, methotrexate, prednisone)
Study groups in NCT04475731
Study groupRoleWhat they receive
Experimental armExperimentalMRD+ Ph+ ALL adult patients will receive Ponatinib x 4 weeks x 3 courses; +/-Concomitant chemotherapy (according to hematologic status). Patients will receive the study drug until disease relapse or progression.
Receives: Drug: Ponatinib

What is being measured

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

  1. MRD negativity/reduction rate

    Rate of patients who achieve a MRD negativity/MRD reduction following treatment with either Ponatinib alone or in combination with systemic chemotherapy

    Measured: After 3 months of treatment

Secondary outcomes (10)

  1. Duration of CMR

    Duration of the CMR status after 3 months of ponatinib treatment

    Measured: at 24 months

  2. Hematologic remission rate

    The achievement of an hematologic remission in patients treated for an hematologic and extra-hematoloigc relapse and for a refractory disease.

    Measured: at 24 months

  3. Best molecular response

    Best molecular response achieved during the follow-up

    Measured: at 24 months

  4. Rate of AE/SAEs

    Safety profile in terms of incidence of grade >3 CTC-NCI side effects and toxicities (AE/SAEs).

    Measured: at 24 months

  5. Mutational analysis

    Mutational analysis in terms of occurrence, type and number of BCR-ABL1 kinase domain mutations.

    Measured: at 24 months

  6. Correlation between biological and MRD parameters

    Correlation between the achievement and duration of CMR (or MRD reduction) with the type of fusion protein (e.g. p190 or p210) and the potential occurrence of mutations, as well as with additional genomic lesions.

    Measured: at 24 months

  7. Disease free survival

    Time interval between the achievement of CHR after three months of ponatinib and hematologic relapse of the disease or death in CHR; patients still alive, in CHR.

    Measured: 24 months

  8. Overall survival

    Time interval between treatment start and death for any cause.

    Measured: 24 months

  9. Cumulative incidence of relapse

    Time interval between achievement of CHR after three months of ponatinib until the date of first hematologic relapse of the disease.

    Measured: 24 months

  10. Role of hematological profile on survival outcome

    Identification of hematological profile on survival outcome

    Measured: at 24 months

Timeline

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

  1. First posted17 Jul 2020
  2. Study start4 May 2021
  3. Primary completionNov 2024 (estimated)
  4. Study completionNov 2024 (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
67 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04475731
Sponsor's protocol ID
ALL2620
Status last verified
Oct 2024
First submitted
25 Jun 2020
Last updated
22 Oct 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ponatinib in people with Philadelphia-Positive ALL and Acute Lymphoblastic Leukemia, in Relapse, run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 22 sites in Italy.

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 11 inclusion and 18 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: status not confirmed, as of the sponsor's last update on 22 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in Italy. 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?

Results are not available in the source record.

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?

MRD negativity/reduction rate (time frame: After 3 months of treatment). 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 NCT04475731.

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 22 Oct 2024.

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