Acute Lymphoblastic Leukemia
Conditions
Keywords
Acute Lymphoblastic Leukemia, adult, dasatinib, blinatumomab
Brief summary
This study aims at exploring the activity of a frontline approach based on dasatinib plus steroids administration as induction treatment, followed by the infusion of Blinatumomab, in adult Ph+ ALL.
Interventions
DRUGDasatinib
Adult Ph+ ALL (≥18 years old, with no upper age limit) patients will begin treatment with Dasatinib, 140 mg/day, from day 1 to day +84.
DRUGBlinatumomab
Upon induction: patients in CHR will receive Blinatumomab at a dose of 15 µg/m²/day as continuous intravenous infusion (CIVI) at a constant flow rate for four weeks, followed by a two-week infusion-free interval, defined as one treatment cycle. At least 2 cycles should be administered, up to a maximum of 5 cycles, if deemed necessary.
Sponsors
Gruppo Italiano Malattie EMatologiche dell'Adulto
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Newly diagnosed adult B-precursor Ph+ ALL patients. * Age greater or equal to18 years, * Signed written informed consent according to ICH/EU/GCP and national local laws. * ECOG Performance Status 0 or 1 and/or WHO performance status less or equal to 2. * Renal and hepatic function as defined below: * AST (GOT), ALT (GPT), and AP \<2 x upper limit of normal (ULN). * 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 * Serum lipase less or equal to1.5 x ULN. * Normal cardiac function. * Negative HIV test, negative HBV DNA and HCV RNA. * Negative pregnancy test in women of childbearing potential. * Bone marrow specimen from primary diagnosis available.
Exclusion criteria
* History of or current relevant CNS pathology (current ≥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. * 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 Dasatinib. * Angina pectoris. * Other clinically significant 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 Dasatinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection). * 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 conditions 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients who achieve Minimal Residual Disease (MRD) negativity upon treatment | After 11 months from study entry | In particular, after 2 cycles of blinatumomab. Minimal Residual Disease (MRD) negativity is intended as Complete Molecular Remission (CMR) |
Secondary
| Measure | Time frame |
|---|---|
| Number of patients completing the 2 cycles of blinatumomab and alive in first complete hematologic remission (CHR) | From day +85 at 12 months |
| Number of patients at Complete Molecular Response (CMR) | At day +22, +45, +57 and +85 from study entry |
| Number of months of the CMR | At 12 and 24 months |
| Number of patients in Overall Survival (OS) | At 12 and 24 months |
| Number of grade >3 adverse events | At 12 and 24 months |
Countries
Italy
Contacts
Primary ContactPaola Fazi
Backup ContactEnrico Crea
Outcome results
None listed