D-ALBA Frontline Sequential Dasatinib and Blinatumomab in Adult Philadelphia Positive Acute Lymphoblastic Leukemia

Overview

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.

Full Title of Study: “D-ALBA Front-Line Sequential Treatment of Adult Philadelphia Chromosome Positive (Ph+) Acute Lymphoblastic Leukemia (ALL) Patients With Dasatinib and the Bispecific Monoclonal Antibody Blinatumomab”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: June 2021

Interventions

  • Drug: Dasatinib
    • 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.
  • Drug: Blinatumomab
    • 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.

Arms, Groups and Cohorts

  • Experimental: Treatment
    • 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. Prednisone (PDN) will be administered from day -6 to day +0 (during which the presence of the BCR/ABL1 alteration will be established), at escalating doses up to 60 mg/m2; PDN will be continued up to day +24 and progressively tapered up to day +31. HLA typing will be performed immediately after the diagnosis for eligible patients. MRD will be evaluated by RT-PCR at fixed time points (days +22, +45, +57) during the induction and at day +85, the latter for molecular response evaluation.

Clinical Trial Outcome Measures

Primary Measures

  • Number of patients who achieve Minimal Residual Disease (MRD) negativity upon treatment
    • Time Frame: 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 Measures

  • Number of patients completing the 2 cycles of blinatumomab and alive in first complete hematologic remission (CHR)
    • Time Frame: From day +85 at 12 months
  • Number of patients at Complete Molecular Response (CMR)
    • Time Frame: At day +22, +45, +57 and +85 from study entry
  • Number of months of the CMR
    • Time Frame: At 12 and 24 months
  • Number of patients in Overall Survival (OS)
    • Time Frame: At 12 and 24 months
  • Number of grade >3 adverse events
    • Time Frame: At 12 and 24 months

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Gruppo Italiano Malattie EMatologiche dell’Adulto
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Roberto Foà, Study Chair, Policlinico Umberto I, Hematology Department.
  • Overall Contact(s)
    • Paola Fazi, +39 06.70390521, p.fazi@gimema.it

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