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

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

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.

Study Overview

Status

Unknown

Study Type

Interventional

Enrollment (Anticipated)

60

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

      • Ascoli Piceno, Italy
        • Not yet recruiting
        • U.O.C. Ematologia e Terapia Cellulare - Ospedale "C. e G. Mazzoni" di Ascoli Piceno
      • Avellino, Italy
        • Not yet recruiting
        • Az.Ospedaliera S.G.Moscati
        • Contact:
          • Nicola Cantore
        • Principal Investigator:
          • Nicola Cantore
      • Bari, Italy
        • Not yet recruiting
        • UO Ematologia con trapianto-Università degli Studi di Bari Aldo Moro
        • Contact:
          • Giorgina Specchia
        • Principal Investigator:
          • Giorgina Specchia
      • Bergamo, Italy
        • Recruiting
        • Azienda Ospedaliera - Papa Giovanni XXIII
        • Contact:
          • Alessandro Rambaldi
        • Principal Investigator:
          • Alessandro Rambaldi
      • Bologna, Italy
        • Not yet recruiting
        • Istituto di Ematologia "Lorenzo e A. Seragnoli" - Università degli Studi di Bologna - Policlinico S. Orsola - Malpighi
        • Contact:
          • Giovanni Martinelli
        • Principal Investigator:
          • Giovanni Martinelli
      • Brindisi, Italy
        • Not yet recruiting
        • Divisione di Ematologia Ospedale A. Perrino
        • Contact:
          • Angela Melpignano
        • Principal Investigator:
          • Angela Melpignano
      • Catania, Italy
        • Recruiting
        • Università di Catania - Cattedra di Ematologia - Ospedale "Ferrarotto"
      • Firenze, Italy
        • Not yet recruiting
        • Unità di Ricerca e di Malattie del sangue - Ematologia San Luca Vecchio Pad. 16 - 1° Piano
        • Contact:
          • Alberto Bosi
      • Genova, Italy
        • Not yet recruiting
        • Unità Operative Complesse di Ematologia 1 e 2 Centro Trapianti di Midollo dell'IRCCS AOU San Martino-IST
        • Contact:
          • Angelo Michele Carella
        • Principal Investigator:
          • Angelo Michele Carella
      • Lecce, Italy
        • Not yet recruiting
        • ASL Le/1 P.O. Vito Fazzi - U.O. di Ematologia ed UTIE
        • Principal Investigator:
          • Nicola Di Renzo
      • Mestre, Italy
        • Recruiting
        • U.O. di Ematologia- Ospedale dell'Angelo - Mestre
        • Principal Investigator:
          • Renato Bassan
        • Contact:
          • Renato Bassan
      • Milano, Italy
        • Recruiting
        • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico UOC Oncoematologia- Padiglione Marcora 2° piano
        • Contact:
          • Agostino Cortelezzi
        • Principal Investigator:
          • Agostino Cortelezzi
      • Milano, Italy
        • Not yet recruiting
        • Ospedale Niguarda " Ca Granda" - SC Ematologia Blocco SUD, Ponti Est, Scala E, 4° piano
        • Contact:
          • Valentina Mancini
        • Principal Investigator:
          • Valentina Mancini
      • Napoli, Italy
        • Recruiting
        • Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli"
        • Contact:
          • Felicetto Ferrara
        • Principal Investigator:
          • Delicetto Ferrara
      • Napoli, Italy
        • Recruiting
        • Azienda Ospedaliera Universitaria - Università degli Studi di Napoli "Federico II" - Facoltà di Medicina e Chirurgia
      • Novara, Italy
        • Recruiting
        • S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro
        • Principal Investigator:
          • Gianluca Gaidano
      • Orbassano, Italy
        • Recruiting
        • Dip. di Scienze Cliniche e Biologiche - Ospedale S. Luigi Gonzaga-Medicina Interna 2
        • Contact:
          • Giovanna Rege
        • Principal Investigator:
          • Giovanna Rege
      • Pagani, Italy
        • Recruiting
        • U.O. di Oncoematologia -plesso ospedaliero "A. Tortora" di Pagani
        • Contact:
          • Castello Califano
        • Principal Investigator:
          • Castello Califano
      • Palermo, Italy
        • Recruiting
        • Ospedali Riuniti "Villa Sofia-Cervello"
        • Contact:
          • Francesco Fabbiano
        • Principal Investigator:
          • Francesco Fabbiano
      • Perugia, Italy
        • Recruiting
        • Sezione di Ematologia ed Immunologia Clinica - Ospedale S.Maria della Misericordia
        • Contact:
          • Brunangelo Falini
        • Principal Investigator:
          • Brunangelo Falini
      • Pescara, Italy
        • Not yet recruiting
        • Ematologia Clinica - Azienda USL di Pescara
        • Contact:
          • Paolo Di Bartolomeo
        • Principal Investigator:
          • Paolo Di Bartolomeo
      • Reggio Calabria, Italy
        • Not yet recruiting
        • Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli"
        • Contact:
          • Francesca Ronco
        • Principal Investigator:
          • Francesca Ronco
      • Roma, Italy
        • Recruiting
        • Complesso Ospedaliero S. Giovanni Addolorata
        • Contact:
          • Anna Chierichini
        • Principal Investigator:
          • Anna Chierichini
      • Roma, Italy
        • Recruiting
        • Università Cattolica del Sacro Cuore - Policlinico A. Gemelli
        • Contact:
          • Simona C Sica
      • Roma, Italy
        • Not yet recruiting
        • Università degli Studi - Policlinico di Tor Vergata
        • Contact:
          • Adriano Venditti
        • Principal Investigator:
          • Adriano Venditti
      • Roma, Italy
        • Not yet recruiting
        • UOC Medicina Trasfusionale e Cellule Staminali Azienda Ospedaliera San Camillo Forlanini
        • Contact:
          • Stefano C Mancini
        • Principal Investigator:
          • Stefano Mancini
      • Rome, Italy
        • Not yet recruiting
        • Policlinico Umberto I, Hematology Department
      • Rome, Italy
        • Recruiting
        • Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia
      • Rozzano, Italy
        • Not yet recruiting
        • Sezione di Ematologia Cancer Center Humanitas
        • Contact:
          • Matteo Della Porta
        • Principal Investigator:
          • Matteo Della Porta
      • San Giovanni Rotondo, Italy
        • Not yet recruiting
        • Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza
      • Torino, Italy
        • Not yet recruiting
        • Dipartimento di Oncologia ed Ematologia S.C. Ematologia 2 A.O. Città della Salute e della Scienza di Torino San Giovanni Battista
      • Torino, Italy
        • Not yet recruiting
        • Struttura Complessa a Dir. Universitaria-Ematologia e Terapie Cellulari- A.S.O. Ordine Mauriziano, P.O. Umberto I-Ospedale Torino
        • Contact:
          • Alessandro Cignetti
        • Principal Investigator:
          • Alessandro Cignetti
      • Torino, Italy
        • Not yet recruiting
        • Struttura Complessa a Dir. Universitaria-Ematologia e Terapie Cellulari- A.S.O. Ordine Mauriziano, P.O. Umberto I-Ospedale
        • Contact:
          • Alessandro Cignetti
        • Principal Investigator:
          • Alessandro Cignetti
      • Verona, Italy
        • Recruiting
        • Università degli Studi di Verona - A. O. - Istituti Ospitalieri di Verona- Div. di Ematologia - Policlinico G.B. Rossi
        • Contact:
          • Massimiliano Bonifacio

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.

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.

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
After 11 months from study entry

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Chair: Roberto Foà, Policlinico Umberto I, Hematology Department.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 31, 2017

Primary Completion (Anticipated)

June 1, 2021

Study Completion (Anticipated)

June 1, 2021

Study Registration Dates

First Submitted

April 11, 2016

First Submitted That Met QC Criteria

April 18, 2016

First Posted (Estimate)

April 20, 2016

Study Record Updates

Last Update Posted (Actual)

March 22, 2018

Last Update Submitted That Met QC Criteria

March 21, 2018

Last Verified

March 1, 2018

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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