Clinical Trials /

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

NCT02744768

Description:

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.

Related Conditions:
  • Acute Lymphoblastic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: D-ALBA Frontline Sequential Dasatinib and Blinatumomab in Adult Philadelphia Positive Acute Lymphoblastic Leukemia
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: LAL2116
  • NCT ID: NCT02744768

Conditions

  • Acute Lymphoblastic Leukemia

Interventions

DrugSynonymsArms
DasatinibTreatment
BlinatumomabTreatment

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
TreatmentExperimentalAdult 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.
  • Dasatinib
  • Blinatumomab

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of patients who achieve Minimal Residual Disease (MRD) negativity upon treatment
Time Frame:After 11 months from study entry
Safety Issue:
Description:In particular, after 2 cycles of blinatumomab. Minimal Residual Disease (MRD) negativity is intended as Complete Molecular Remission (CMR)

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:
Measure:Number of patients at Complete Molecular Response (CMR)
Time Frame:At day +22, +45, +57 and +85 from study entry
Safety Issue:
Description:
Measure:Number of months of the CMR
Time Frame:At 12 and 24 months
Safety Issue:
Description:
Measure:Number of patients in Overall Survival (OS)
Time Frame:At 12 and 24 months
Safety Issue:
Description:
Measure:Number of grade >3 adverse events
Time Frame:At 12 and 24 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Gruppo Italiano Malattie EMatologiche dell'Adulto

Trial Keywords

  • Acute Lymphoblastic Leukemia, adult, dasatinib, blinatumomab

Last Updated

March 21, 2018