Clinical trial NCT02744768: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Acute Lymphoblastic Leukemia
Keywords: Acute Lymphoblastic Leukemia, adult, dasatinib, blinatumomab
Lead sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto
Sponsor class: OTHER
First posted: 2016-04-20
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of patients who achieve Minimal Residual Disease (MRD) negativity upon treatment
timeFrame: After 11 months from study entry
Secondary outcomes:
measure: Number of patients completing the 2 cycles of blinatumomab and alive in first complete hematologic remission (CHR)
timeFrame: From day +85 at 12 months
measure: Number of patients at Complete Molecular Response (CMR)
timeFrame: At day +22, +45, +57 and +85 from study entry
measure: Number of months of the CMR
timeFrame: At 12 and 24 months
measure: Number of patients in Overall Survival (OS)
timeFrame: At 12 and 24 months
measure: Number of grade >3 adverse events
timeFrame: At 12 and 24 months
Other outcomes:
Locations:
city: Ascoli Piceno
country: Italy
facility: U.O.C. Ematologia e Terapia Cellulare - Ospedale "C. e G. Mazzoni" di Ascoli Piceno
city: Avellino
country: Italy
facility: Az.Ospedaliera S.G.Moscati
city: Bari
country: Italy
facility: UO Ematologia con trapianto-Università degli Studi di Bari Aldo Moro
city: Bergamo
country: Italy
facility: Azienda Ospedaliera - Papa Giovanni XXIII
city: Bologna
country: Italy
facility: Istituto di Ematologia "Lorenzo e A. Seragnoli" - Università degli Studi di Bologna - Policlinico S. Orsola - Malpighi
city: Brindisi
country: Italy
facility: Divisione di Ematologia Ospedale A. Perrino
city: Catania
country: Italy
facility: Università di Catania - Cattedra di Ematologia - Ospedale "Ferrarotto"
city: Firenze
country: Italy
facility: Unità di Ricerca e di Malattie del sangue - Ematologia San Luca Vecchio Pad. 16 - 1° Piano
city: Genova
country: Italy
facility: Unità Operative Complesse di Ematologia 1 e 2 Centro Trapianti di Midollo dell'IRCCS AOU San Martino-IST
city: Lecce
country: Italy
facility: ASL Le/1 P.O. Vito Fazzi - U.O. di Ematologia ed UTIE
city: Mestre
country: Italy
facility: U.O. di Ematologia- Ospedale dell'Angelo - Mestre
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico UOC Oncoematologia- Padiglione Marcora 2° piano
city: Milano
country: Italy
facility: Ospedale Niguarda " Ca Granda" - SC Ematologia Blocco SUD, Ponti Est, Scala E, 4° piano
city: Napoli
country: Italy
facility: Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli"
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria - Università degli Studi di Napoli "Federico II" - Facoltà di Medicina e Chirurgia
city: Novara
country: Italy
facility: S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro
city: Orbassano
country: Italy
facility: Dip. di Scienze Cliniche e Biologiche - Ospedale S. Luigi Gonzaga-Medicina Interna 2
city: Pagani
country: Italy
facility: U.O. di Oncoematologia -plesso ospedaliero "A. Tortora" di Pagani
city: Palermo
country: Italy
facility: Ospedali Riuniti "Villa Sofia-Cervello"
city: Perugia
country: Italy
facility: Sezione di Ematologia ed Immunologia Clinica - Ospedale S.Maria della Misericordia
city: Pescara
country: Italy
facility: Ematologia Clinica - Azienda USL di Pescara
city: Reggio Calabria
country: Italy
facility: Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli"
city: Roma
country: Italy
facility: Complesso Ospedaliero S. Giovanni Addolorata
city: Roma
country: Italy
facility: Università Cattolica del Sacro Cuore - Policlinico A. Gemelli
city: Roma
country: Italy
facility: Università degli Studi - Policlinico di Tor Vergata
city: Roma
country: Italy
facility: UOC Medicina Trasfusionale e Cellule Staminali Azienda Ospedaliera San Camillo Forlanini
city: Rome
country: Italy
facility: Policlinico Umberto I, Hematology Department
city: Rome
country: Italy
facility: Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia
city: Rozzano
country: Italy
facility: Sezione di Ematologia Cancer Center Humanitas
city: San Giovanni Rotondo
country: Italy
facility: Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza
city: Torino
country: Italy
facility: Dipartimento di Oncologia ed Ematologia S.C. Ematologia 2 A.O. Città della Salute e della Scienza di Torino San Giovanni Battista
city: Torino
country: Italy
facility: Struttura Complessa a Dir. Universitaria-Ematologia e Terapie Cellulari- A.S.O. Ordine Mauriziano, P.O. Umberto I-Ospedale Torino
city: Torino
country: Italy
facility: Struttura Complessa a Dir. Universitaria-Ematologia e Terapie Cellulari- A.S.O. Ordine Mauriziano, P.O. Umberto I-Ospedale
city: Verona
country: Italy
facility: Università degli Studi di Verona - A. O. - Istituti Ospitalieri di Verona- Div. di Ematologia - Policlinico G.B. Rossi
Study officials:
affiliation: Policlinico Umberto I, Hematology Department.
name: Roberto Foà
role: STUDY_CHAIR
References:
citation: Foa 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.