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.
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
- Conditions the study is for
- Acute Lymphoblastic Leukemia (Philadelphia Chromosome Positive), ALL, Adult, Philadelphia-Positive ALL
- 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
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).
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- 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.
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- 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
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.
- Conditions
- Acute Lymphoblastic Leukemia (Philadelphia Chromosome Positive), ALL, Adult, Philadelphia-Positive ALL
- 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 group | Role | What they receive |
|---|---|---|
| Ponatinib+Blinatumomab | Experimental | patients will receive induction with ponatinib followed by at least 2 cycles of blinatumomab Receives: Drug: Ponatinib + Blinatumomab |
| Chemotherapy+Imatinib | Active comparator | patients 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.
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.
- First posted25 Jan 2021
- Study start8 Sep 2021
- Primary completionSep 2027 (estimated)
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Lymphoblastic Leukemia (Philadelphia Chromosome Positive)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- Gruppo Italiano Malattie EMatologiche dell'Adulto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
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