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
1 other identifier
interventional
60
1 country
34
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started May 2017
Typical duration for phase_2
34 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 11, 2016
CompletedFirst Posted
Study publicly available on registry
April 20, 2016
CompletedStudy Start
First participant enrolled
May 31, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2021
CompletedMarch 22, 2018
March 1, 2018
4 years
April 11, 2016
March 21, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of patients who achieve Minimal Residual Disease (MRD) negativity upon treatment
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 Outcomes (5)
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
Study Arms (1)
Treatment
EXPERIMENTALAdult 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
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.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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).
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (34)
U.O.C. Ematologia e Terapia Cellulare - Ospedale "C. e G. Mazzoni" di Ascoli Piceno
Ascoli Piceno, Italy
Az.Ospedaliera S.G.Moscati
Avellino, Italy
UO Ematologia con trapianto-Università degli Studi di Bari Aldo Moro
Bari, Italy
Azienda Ospedaliera - Papa Giovanni XXIII
Bergamo, Italy
Istituto di Ematologia "Lorenzo e A. Seragnoli" - Università degli Studi di Bologna - Policlinico S. Orsola - Malpighi
Bologna, Italy
Divisione di Ematologia Ospedale A. Perrino
Brindisi, Italy
Università di Catania - Cattedra di Ematologia - Ospedale "Ferrarotto"
Catania, Italy
Unità di Ricerca e di Malattie del sangue - Ematologia San Luca Vecchio Pad. 16 - 1° Piano
Florence, Italy
Unità Operative Complesse di Ematologia 1 e 2 Centro Trapianti di Midollo dell'IRCCS AOU San Martino-IST
Genova, Italy
ASL Le/1 P.O. Vito Fazzi - U.O. di Ematologia ed UTIE
Lecce, Italy
U.O. di Ematologia- Ospedale dell'Angelo - Mestre
Mestre, Italy
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico UOC Oncoematologia- Padiglione Marcora 2° piano
Milan, Italy
Ospedale Niguarda " Ca Granda" - SC Ematologia Blocco SUD, Ponti Est, Scala E, 4° piano
Milan, Italy
Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli"
Napoli, Italy
Azienda Ospedaliera Universitaria - Università degli Studi di Napoli "Federico II" - Facoltà di Medicina e Chirurgia
Napoli, Italy
S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro
Novara, Italy
Dip. di Scienze Cliniche e Biologiche - Ospedale S. Luigi Gonzaga-Medicina Interna 2
Orbassano, Italy
U.O. di Oncoematologia -plesso ospedaliero "A. Tortora" di Pagani
Pagani, Italy
Ospedali Riuniti "Villa Sofia-Cervello"
Palermo, Italy
Sezione di Ematologia ed Immunologia Clinica - Ospedale S.Maria della Misericordia
Perugia, Italy
Ematologia Clinica - Azienda USL di Pescara
Pescara, Italy
Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli"
Reggio Calabria, Italy
Complesso Ospedaliero S. Giovanni Addolorata
Roma, Italy
Università Cattolica del Sacro Cuore - Policlinico A. Gemelli
Roma, Italy
Università degli Studi - Policlinico di Tor Vergata
Roma, Italy
UOC Medicina Trasfusionale e Cellule Staminali Azienda Ospedaliera San Camillo Forlanini
Roma, Italy
Policlinico Umberto I, Hematology Department
Rome, Italy
Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia
Rome, Italy
Sezione di Ematologia Cancer Center Humanitas
Rozzano, Italy
Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza
San Giovanni Rotondo, Italy
Dipartimento di Oncologia ed Ematologia S.C. Ematologia 2 A.O. Città della Salute e della Scienza di Torino San Giovanni Battista
Torino, Italy
Struttura Complessa a Dir. Universitaria-Ematologia e Terapie Cellulari- A.S.O. Ordine Mauriziano, P.O. Umberto I-Ospedale Torino
Torino, Italy
Struttura Complessa a Dir. Universitaria-Ematologia e Terapie Cellulari- A.S.O. Ordine Mauriziano, P.O. Umberto I-Ospedale
Torino, Italy
Università degli Studi di Verona - A. O. - Istituti Ospitalieri di Verona- Div. di Ematologia - Policlinico G.B. Rossi
Verona, Italy
Related Publications (2)
Foa R, Bassan R, Elia L, Piciocchi A, Soddu S, Messina M, Ferrara F, Lunghi M, Mule A, Bonifacio M, Fracchiolla N, Salutari P, Fazi P, Guarini A, Rambaldi A, Chiaretti S. Long-Term Results of the Dasatinib-Blinatumomab Protocol for Adult Philadelphia-Positive ALL. J Clin Oncol. 2024 Mar 10;42(8):881-885. doi: 10.1200/JCO.23.01075. Epub 2023 Dec 21.
PMID: 38127722DERIVEDFoa 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.
PMID: 33085860DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Roberto Foà
Policlinico Umberto I, Hematology Department.
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 11, 2016
First Posted
April 20, 2016
Study Start
May 31, 2017
Primary Completion
June 1, 2021
Study Completion
June 1, 2021
Last Updated
March 22, 2018
Record last verified: 2018-03
Data Sharing
- IPD Sharing
- Will not share