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Acute Lymphoblastic Leukemia (Philadelphia Chromosome Positive)Phase 3NCT04722848

Sequential Treatment With Ponatinib and Blinatumomab vs Chemotherapy and Imatinib in Newly Diagnosed Adult Ph+ ALL

A Phase 3 study testing Ponatinib + Blinatumomab and Chemotherapy + Imatinib in people with Acute Lymphoblastic Leukemia (Philadelphia Chromosome Positive) and ALL, Adult, run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 15 sites in Italy.

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

This is a randomised, open-label, multicenter, phase III study for adult de novo Ph+ ALL patients based on the combination of Ponatinib with Blinatumomab. The control arm will be represented by a chemotherapeutic scheme combined with Imatinib for patients aged 18-65 and by Imatinib plus age-adjusted chemotherapy for… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ponatinib + Blinatumomab and Chemotherapy + Imatinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
236 participants
Where
15 sitesItaly
Study dates
8 Sep 2021to Sep 2027
Phase
Phase 3
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed written informed consent according to ICH/EU/GCP and national local laws.
  • Newly diagnosed adult B-precursor Ph+ ALL patients.
  • WHO performance status less or equal to 2.
  • Age greater or equal to18 years, with no upper age limit.
  • Renal and hepatic function as defined below:
  • AST (GOT), ALT (GPT), and AP <2 x upper limit of normal (ULN).
Show all 15Show fewer
  • Total bilirubin <1.5 x ULN.
  • Creatinine clearance equal or greater than 50 mL/min.
  • Pancreatic function as defined below:
  • Serum amylase less or equal to 1.5 x ULN and serum lipase less or equal to1.5 x ULN.
  • Normal cardiac function.
  • No evidence of CNS leukemia at blinatumomab start.
  • Negative HIV test, negative hepatitis B (HBsAg) and hepatitis C virus (anti-HCV) test.
  • Negative pregnancy test in women of childbearing potential.
  • Bone marrow specimen from primary diagnosis available.

Who cannot join

  • History of or current relevant CNS pathology (ongoing grade ≥2 epilepsy, seizure, paresis, aphasia, clinically relevant apoplexia, severe brain injuries, dementia, Parkinson's disease, organic brain syndrome, psychosis).
  • Impaired cardiac function, including any one of the following:
  • LVEF <45% as determined by MUGA scan or echocardiogram.
  • Complete left bundle branch block.
  • Use of a cardiac pacemaker.
  • ST depression of >1mm in 2 or more leads and/or T wave inversions in 2 or more contiguous leads.
Show all 23Show fewer
  • Congenital long QT syndrome.
  • History of or presence of significant ventricular or atrial arrhythmia.
  • Clinically significant resting bradycardia (<50 beats per minute).
  • QTc >450 msec on screening ECG (using the QTcF formula).
  • Right bundle branch block plus left anterior hemiblock, bifascicular block.
  • Myocardial infarction within 3 months prior to starting Ponatinib.
  • Angina pectoris.
  • Other clinically significant vascular and heart disease (e.g., congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen).
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of Ponatinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
  • Uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL).
  • Taking medications that are known to be associated with Torsades de Pointes and medications or herbal supplements that are known to be strong inhibitors of CYP3A4 within at least 14 days before the first dose of ponatinib.
  • History of or current autoimmune disease.
  • Systemic cancer chemotherapy within 2 weeks prior to study.
  • Known hypersensitivity to immunoglobulins or to any other component of the study drug formulation.
  • Active malignancy other than ALL with the exception of basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix.
  • Active infection, any other concurrent disease or medical condition that are deemed to interfere with the conduct of the study as judged by the investigator.
  • Nursing women or women of childbearing potential not willing to use an effective form of contraception during participation in the study and at least 3 months thereafter or male patients not willing to ensure effective contraception during participation in the study and at least three months thereafter.

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

Italy15 sites

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

    Ascoli Piceno

  • Irccs Oncologico Istituto Tumori Giovanni Paolo Ii - Bari - Uo Ematologia

    Bari

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

    Bergamo

  • As Dell'Alto Adige, Ospedale Centrale Di Bolzano - Ematologia E Centro Trapianto Midollo Osseo

    Bolzano

  • Asst Degli Spedali Civili Di Brescia - Uo Ematologia

    Brescia

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

    Mestre

  • Aou Di Modena - Sc Ematologia

    Modena

  • Asl Salerno, Presidio Ospedaliero Tortora Pagani - Ematologia

    Pagani

  • 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

  • Asl Di Piacenza, Ospedale "Guglielmo Da Saliceto" - Ematologia E Centro Trapianti

    Piacenza

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

    Roma

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

    San Giovanni Rotondo

  • Aou Senese - Uoc Ematologia E Trapianti

    Siena

  • Asui Di Udine - Presidio Ospedaliero "Santa Maria Della Misericordia" - Clinica Ematologica

    Udine

Other trials in Italy

About this study

Official title: Newly Diagnosed Adult Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL). Sequential Treatment With Ponatinib and the Bispecific Monoclonal Antibody Blinatumomab vs Chemotherapy and Imatinib

This is a randomised, open-label, multicenter, phase III study for adult de novo Ph+ ALL patients based on the combination of Ponatinib with Blinatumomab. The control arm will be represented by a chemotherapeutic scheme combined with Imatinib for patients aged 18-65 and by Imatinib plus age-adjusted chemotherapy for elderly patients (>65 years old).

Patients will be randomized 2:1 to receive the experimental or control arm. If patients in the control arm do not achieve a CHR and/or MRD negativity, after the sixth consolidation cycle (week 20), a crossover to receive Blinatumomab is planned. Likewise, if patients in the control arm develop an ABL1 mutation at any time of treatment, they will switch to experimental arm. HLA typing will be performed immediately after diagnosis in both arms for patients aged up to 65 years.

After the 2 cycles of Blinatumomab in the experimental arm and after consolidation in the control arm, patients aged 18-65 will be stratified for transplant allocation.

Read the detailed description

This is a randomised, open-label, multicenter, phase III study for adult de novo Ph+ ALL patients (≥18 years, no upper age-limit) based on the combination of the pan-TKI Ponatinib, with the bispecific monoclonal antibody Blinatumomab. The control arm will be represented by a chemotherapeutic scheme combined with Imatinib for patients aged 18-65 and by Imatinib plus age-adjusted chemotherapy for elderly patients (>65 years old).

Patients (≥18 years, no upper age limit) will be randomized 2:1 to receive the experimental or control arm. If patients in the control arm do not achieve a CHR and/or MRD negativity, after the sixth consolidation cycle (week 20), a crossover to receive Blinatumomab is planned. Likewise, if patients in the control arm develop an ABL1 mutation at any time of treatment, they will switch to experimental arm. HLA typing will be performed immediately after diagnosis in both arms for patients aged up to 65 years.

After the 2 cycles of Blinatumomab in the experimental arm and after consolidation in the control arm, patients aged 18-65 will be stratified for transplant allocation.

Being tested
Ponatinib + Blinatumomab, Chemotherapy + Imatinib
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.

  • Ponatinib + BlinatumomabDrug

    Patients aged 18-65 will receive Ponatinib at the dose of 45 mg/day for the first 22 days and then will reduce the dose to 30 mg (depending on the morphologic and molecular response), whereas patients older than 65 years will start Ponatinib at 30 mg/day, in order to avoid TAEs. Patients will continue treatment with Ponatinib up to day 70 (10 weeks of treatment), except for disease progression, intolerable toxicity, or withdrawal from study. Thereafter:

    • Patients will receive Blinatumomab (minimum 2 cycles, up to a maximum of 5).
    • Patients not achieving a CHR after 2 cycles of Blinatumomab will go off-study. After the 2 cycles of Blinatumomab patients aged 18-65 will be stratified for transplant allocation

  • Chemotherapy + ImatinibDrug

    patients aged 18-65 will receive chemotherapeutic scheme combined with Imatinib. Elderly patients will receive Imatinib plus mild chemotherapy.

Study groups in NCT04722848
Study groupRoleWhat they receive
Ponatinib+BlinatumomabExperimentalpatients will receive induction with ponatinib followed by at least 2 cycles of blinatumomab
Receives: Drug: Ponatinib + Blinatumomab
Chemotherapy+ImatinibActive comparatorpatients will receive a combination of imatinib and chemotherapy.
Receives: Drug: Chemotherapy + Imatinib

What is being measured

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

  1. Number of patients who are event-free

    event-free survival rate

    Measured: at 5 months

Timeline

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

  1. First posted25 Jan 2021
  2. Study start8 Sep 2021
  3. Primary completionSep 2027 (estimated)
  4. Study completionSep 2027 (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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
236 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04722848
Sponsor's protocol ID
ALL2820
Status last verified
Jan 2025
First submitted
20 Jan 2021
Last updated
23 Jan 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Chiaretti S, Piciocchi A, Skert C, Leoncin M, Borlenghi E, Cattaneo C, Di Trani M, Elia L, Almici G, Cardinali D, Kaiser F, Lussana F, Fiumara PF, Maugeri C, Alati C, Martino M, Ansuinelli M, Lucco Navei G, Mattei D, Soddu S, Messina M, Marino MR, Mancini V, Chiusolo P, Scappini B, Martelli MP, Salutari P, Cerrano M, Serio B, Cucca A, Luppi M, Pochintesta L, Pasciolla C, Romani C, Mosna F, Bonifacio M, Tanasi I, Fracchiolla NS, Bocchia M, Imbergamo S, Califano C, Nunziata GR, Annunziata M, Mule A, Zappasodi P, Mastaglio S, Butera S, Della Porta MG, Porretto F, Lunghi M, De Bellis E, Todisco E, Basilico CM, Fazi P, Rambaldi A, Bassan R, Foa R; GIMEMA Investigators. Ponatinib-Blinatumomab or Imatinib-Chemotherapy for Adult Ph-Positive ALL. N Engl J Med. 2026 Oct 15;395(15):1483-1494. doi: 10.1056/NEJMoa2606208.

    PubMed 42874102

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ponatinib + Blinatumomab and Chemotherapy + Imatinib in people with Acute Lymphoblastic Leukemia (Philadelphia Chromosome Positive) and ALL, Adult, run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 15 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 15 inclusion and 23 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 23 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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?

Number of patients who are event-free (time frame: at 5 months). 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 NCT04722848, which also lists 1 linked publication.

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 23 Jan 2025.

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