Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Philadelphia Chromosome

Lymphoma

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Translocation, Genetic

Chromosome Aberrations

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Lymphosarcoma

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Blinatumomab

Ponatinib

Imatinib Mesylate

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

patients will receive induction with ponatinib followed by at least 2 cycles of blinatumomab

patients will receive a combination of imatinib and chemotherapy.

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

Ponatinib + Blinatumomab

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

Chemotherapy + Imatinib

Paola Fazi

Enrico Crea

Piero Galieno

Crescenza Pasciolla

Alessandro Rambaldi

Federico Mosna

Erika Borlenghi

Renato U Bassan

Mario Luppi

Catello Califano

Maria Paola Martelli

Giuseppe Visani

Daniele C Vallisa

Sabina Chiaretti

Nicola Cascavilla

Monica Bocchia

Anna Candoni

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.

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.

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

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

Gruppo Italiano Malattie EMatologiche dell'Adulto

Spots Global Cancer Trial Database for chemotherapy + imatinib