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

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ClinicalTrials.gov Identifier: NCT02744768
Recruitment Status : Recruiting
First Posted : April 20, 2016
Last Update Posted : March 22, 2018
Sponsor:
Information provided by (Responsible Party):
Gruppo Italiano Malattie EMatologiche dell'Adulto

Tracking Information
First Submitted Date  ICMJE April 11, 2016
First Posted Date  ICMJE April 20, 2016
Last Update Posted Date March 22, 2018
Actual Study Start Date  ICMJE May 31, 2017
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 18, 2016)
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)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 18, 2016)
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE D-ALBA Frontline Sequential Dasatinib and Blinatumomab in Adult Philadelphia Positive Acute Lymphoblastic Leukemia
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Lymphoblastic Leukemia
Intervention  ICMJE
  • 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.

Study Arms  ICMJE 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.

Interventions:
  • Drug: Dasatinib
  • Drug: Blinatumomab
Publications * Foà R, Bassan R, Vitale A, Elia L, Piciocchi A, Puzzolo MC, Canichella M, Viero P, Ferrara F, Lunghi M, Fabbiano F, Bonifacio M, Fracchiolla N, Di Bartolomeo P, Mancino A, De Propris MS, Vignetti M, Guarini A, Rambaldi A, Chiaretti S; GIMEMA Investigators. Dasatinib-Blinatumomab for Ph-Positive Acute Lymphoblastic Leukemia in Adults. N Engl J Med. 2020 Oct 22;383(17):1613-1623. doi: 10.1056/NEJMoa2016272.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 18, 2016)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2021
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Paola Fazi +39 06.70390521 p.fazi@gimema.it
Contact: Enrico Crea +39 0670390514 e.crea@gimema.it
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02744768
Other Study ID Numbers  ICMJE LAL2116
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Gruppo Italiano Malattie EMatologiche dell'Adulto
Study Sponsor  ICMJE Gruppo Italiano Malattie EMatologiche dell'Adulto
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Roberto Foà Policlinico Umberto I, Hematology Department.
PRS Account Gruppo Italiano Malattie EMatologiche dell'Adulto
Verification Date March 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP