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

NCT ID: NCT02744768

Last Updated: 2018-03-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-05-31

Study Completion Date

2021-06-30

Brief Summary

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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

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Conditions

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Acute Lymphoblastic Leukemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Dasatinib

Intervention Type DRUG

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

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gruppo Italiano Malattie EMatologiche dell'Adulto

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Roberto Foà

Role: STUDY_CHAIR

Policlinico Umberto I, Hematology Department.

Locations

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U.O.C. Ematologia e Terapia Cellulare - Ospedale "C. e G. Mazzoni" di Ascoli Piceno

Ascoli Piceno, , Italy

Site Status NOT_YET_RECRUITING

Az.Ospedaliera S.G.Moscati

Avellino, , Italy

Site Status NOT_YET_RECRUITING

UO Ematologia con trapianto-Università degli Studi di Bari Aldo Moro

Bari, , Italy

Site Status NOT_YET_RECRUITING

Azienda Ospedaliera - Papa Giovanni XXIII

Bergamo, , Italy

Site Status RECRUITING

Istituto di Ematologia "Lorenzo e A. Seragnoli" - Università degli Studi di Bologna - Policlinico S. Orsola - Malpighi

Bologna, , Italy

Site Status NOT_YET_RECRUITING

Divisione di Ematologia Ospedale A. Perrino

Brindisi, , Italy

Site Status NOT_YET_RECRUITING

Università di Catania - Cattedra di Ematologia - Ospedale "Ferrarotto"

Catania, , Italy

Site Status RECRUITING

Unità di Ricerca e di Malattie del sangue - Ematologia San Luca Vecchio Pad. 16 - 1° Piano

Florence, , Italy

Site Status NOT_YET_RECRUITING

Unità Operative Complesse di Ematologia 1 e 2 Centro Trapianti di Midollo dell'IRCCS AOU San Martino-IST

Genova, , Italy

Site Status NOT_YET_RECRUITING

ASL Le/1 P.O. Vito Fazzi - U.O. di Ematologia ed UTIE

Lecce, , Italy

Site Status NOT_YET_RECRUITING

U.O. di Ematologia- Ospedale dell'Angelo - Mestre

Mestre, , Italy

Site Status RECRUITING

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico UOC Oncoematologia- Padiglione Marcora 2° piano

Milan, , Italy

Site Status RECRUITING

Ospedale Niguarda " Ca Granda" - SC Ematologia Blocco SUD, Ponti Est, Scala E, 4° piano

Milan, , Italy

Site Status NOT_YET_RECRUITING

Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli"

Napoli, , Italy

Site Status RECRUITING

Azienda Ospedaliera Universitaria - Università degli Studi di Napoli "Federico II" - Facoltà di Medicina e Chirurgia

Napoli, , Italy

Site Status RECRUITING

S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro

Novara, , Italy

Site Status RECRUITING

Dip. di Scienze Cliniche e Biologiche - Ospedale S. Luigi Gonzaga-Medicina Interna 2

Orbassano, , Italy

Site Status RECRUITING

U.O. di Oncoematologia -plesso ospedaliero "A. Tortora" di Pagani

Pagani, , Italy

Site Status RECRUITING

Ospedali Riuniti "Villa Sofia-Cervello"

Palermo, , Italy

Site Status RECRUITING

Sezione di Ematologia ed Immunologia Clinica - Ospedale S.Maria della Misericordia

Perugia, , Italy

Site Status RECRUITING

Ematologia Clinica - Azienda USL di Pescara

Pescara, , Italy

Site Status NOT_YET_RECRUITING

Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli"

Reggio Calabria, , Italy

Site Status NOT_YET_RECRUITING

Complesso Ospedaliero S. Giovanni Addolorata

Roma, , Italy

Site Status RECRUITING

Università Cattolica del Sacro Cuore - Policlinico A. Gemelli

Roma, , Italy

Site Status RECRUITING

Università degli Studi - Policlinico di Tor Vergata

Roma, , Italy

Site Status NOT_YET_RECRUITING

UOC Medicina Trasfusionale e Cellule Staminali Azienda Ospedaliera San Camillo Forlanini

Roma, , Italy

Site Status NOT_YET_RECRUITING

Policlinico Umberto I, Hematology Department

Rome, , Italy

Site Status NOT_YET_RECRUITING

Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia

Rome, , Italy

Site Status RECRUITING

Sezione di Ematologia Cancer Center Humanitas

Rozzano, , Italy

Site Status NOT_YET_RECRUITING

Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, , Italy

Site Status 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

Site Status NOT_YET_RECRUITING

Struttura Complessa a Dir. Universitaria-Ematologia e Terapie Cellulari- A.S.O. Ordine Mauriziano, P.O. Umberto I-Ospedale Torino

Torino, , Italy

Site Status NOT_YET_RECRUITING

Struttura Complessa a Dir. Universitaria-Ematologia e Terapie Cellulari- A.S.O. Ordine Mauriziano, P.O. Umberto I-Ospedale

Torino, , Italy

Site Status NOT_YET_RECRUITING

Università degli Studi di Verona - A. O. - Istituti Ospitalieri di Verona- Div. di Ematologia - Policlinico G.B. Rossi

Verona, , Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Paola Fazi

Role: CONTACT

+39 06.70390521

Enrico Crea

Role: CONTACT

+39 0670390514

Facility Contacts

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Piero Galieni

Role: primary

Nicola Cantore

Role: primary

Giorgina Specchia

Role: primary

Alessandro Rambaldi

Role: primary

Giovanni Martinelli

Role: primary

Angela Melpignano

Role: primary

Francesco Di Raimondo

Role: primary

Alberto Bosi

Role: primary

Angelo Michele Carella

Role: primary

Nicola Di Renzo

Role: primary

Renato Bassan

Role: primary

Agostino Cortelezzi

Role: primary

Valentina Mancini

Role: primary

Felicetto Ferrara

Role: primary

Fabrizio Pane

Role: primary

Gianluca Gaidano

Role: primary

Giovanna Rege

Role: primary

Castello Califano

Role: primary

Francesco Fabbiano

Role: primary

Brunangelo Falini

Role: primary

Paolo Di Bartolomeo

Role: primary

Francesca Ronco

Role: primary

Anna Chierichini

Role: primary

Simona C Sica

Role: primary

Adriano Venditti

Role: primary

Stefano C Mancini

Role: primary

Roberto Foà

Role: primary

Roberto Foà

Role: primary

Matteo Della Porta

Role: primary

Nicola Cascavilla

Role: primary

Ernesta Audisio

Role: primary

Alessandro Cignetti

Role: primary

Alessandro Cignetti

Role: primary

Massimiliano Bonifacio

Role: primary

References

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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.

Reference Type DERIVED
PMID: 38127722 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33085860 (View on PubMed)

Provided Documents

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Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Related Links

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http://www.gimema.it

GIMEMA Foundation website

Other Identifiers

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LAL2116

Identifier Type: -

Identifier Source: org_study_id

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