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

Acute Lymphoblastic Leukemia Clinical Trial

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 Details — Status: Recruiting

Administrative data

• NCT number: NCT02744768
• Other study ID #: LAL2116
• Status: Recruiting
• Phase: Phase 2
• First received: April 11, 2016
• Last updated: March 21, 2018
• Start date: May 31, 2017
• Est. completion date: June 2021

Study information

• Verified date: March 2018
• Source: Gruppo Italiano Malattie EMatologiche dell'Adulto
• Contact: Paola Fazi
• Phone: +39 06.70390521
• Email: p.fazi[@]gimema.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: June 2021
• Est. primary completion date: June 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

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.
• 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.

Locations

Country	Name	City	State
Italy	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	Firenze
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	Milano
Italy	Ospedale Niguarda " Ca Granda" - SC Ematologia Blocco SUD, Ponti Est, Scala E, 4° piano	Milano
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
Italy	Struttura Complessa a Dir. Universitaria-Ematologia e Terapie Cellulari- A.S.O. Ordine Mauriziano, P.O. Umberto I-Ospedale Torino	Torino
Italy	Università degli Studi di Verona - A. O. - Istituti Ospitalieri di Verona- Div. di Ematologia - Policlinico G.B. Rossi	Verona

Sponsors (1)

Lead Sponsor	Collaborator
Gruppo Italiano Malattie EMatologiche dell'Adulto

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Number of patients completing the 2 cycles of blinatumomab and alive in first complete hematologic remission (CHR)		From day +85 at 12 months
Secondary	Number of patients at Complete Molecular Response (CMR)		At day +22, +45, +57 and +85 from study entry
Secondary	Number of months of the CMR		At 12 and 24 months
Secondary	Number of patients in Overall Survival (OS)		At 12 and 24 months
Secondary	Number of grade >3 adverse events		At 12 and 24 months

External Links

•   GIMEMA Foundation website