Clinical trial NCT03367299: Sequential Chemotherapy and Blinatumomab to Improve MRD Response and Survival in Acute Lymphoblastic Leukemia
Official title: National Treatment Program With Sequential Chemotherapy and Blinatumomab to Improve Minimal Residual Disease Response and Survival in Philadelphia Chromosome-Negative B-Cell Precursor Adult Acute Lymphoblastic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Lymphoid Leukemia
Philadelphia Chromosome-Negative B-Cell Precursor
Keywords: Acute Lymphoid Leukemia
Philadelphia Chromosome-Negative B-Cell Precursor
Adults
Minimal residual disease
Blinatumomab
Lead sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto
Sponsor class: OTHER
First posted: 2017-12-08
Enrollment: 149
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The present study aims at analyzing the response to treatment of adult patients homogeneously treated with supportive care, chemotherapy and blinatumomab.

Detailed description: Eligible patients with CD19+ Ph- BCP ALL (Philadelphia-negative B-cell precursor acute lymphoblastic leukemia) will receive homogeneous supportive care, chemotherapy and blinatumomab immunotherapy, and will be homogeneously analyzed for response at prefixed time points from induction day 1. For risk-oriented therapy, patients in complete remission (CR) will be stratified by risk class according to the diagnostic characteristics and MRD (minimal residual disease) study results during early consolidation.

Eligibility criteria: Inclusion Criteria:

* Signed written informed consent according to ICH/EU/GCP and national local laws.
* Age 18-65 years.
* A diagnosis of untreated Ph- CD19+ BCP ALL is required, either de novo or secondary to chemo-radiotherapy for another cancer. Pre-treatment with low-dose corticosteroids in patients presenting with hyperleukocytosis is allowed. Before enrolment and pre-phase is allowed only in patients presenting with severe, potentially life-threatening disease-related clinical symptoms. All diagnostic procedures need to be performed on freshly obtained bone marrow (BM) and peripheral blood (PB) samples.
* Full cytological, cytochemical, immunophenotypic, cytogenetic and molecular disease characterization according to the EGIL and WHO classifications.
* BM and PB sampling for MRD evaluations study. Detailed indications on patient registration, storage of representative diagnostic material and diagnostic work-up, including the shipping of samples for the diagnostic work-up and MRD follow-up studies are given in Appendix A.
* An ECOG performance status 0-2, unless a performance of 3 is unequivocally caused by the disease itself, (and not by pre-existing comorbidities,) and is considered and/or documented to be reversible following the application of anti-leukemic therapy and appropriate supportive measures.

Exclusion Criteria:

* Diagnosis of Burkitt's leukemia/lymphoma, CD19- BCP ALL, Ph+ ALL, T-ALL, lymphoblastic lymphoma (BM involvement by blast cells \<25%).
* Active CNS leukemia documented by diagnostic lumbar puncture on days -1 to -5 prior to the first blinatumomab administration, or any other clinical sign or symptom ascribable to symptomatic/documented CNS disease at time of each planned blinatumomab course.
* Down's syndrome.
* A pre-existing, uncontrolled pathology such as heart failure (congestive/ischemic, acute myocardial infarction within the past 3 months, untreatable arrhythmias, NYHA classes III and IV), severe liver disease with serum bilirubin \>3 mg/dL and/or ALT \>3 x upper normal limit (unless attributable to ALL), kidney function impairment with serum creatinine \>2 mg/dL (unless attributable to ALL), and severe neuropsychiatric disorder that impairs the patient's ability to understand and sign the informed consent, or to cope with the intended treatment plan. N.B. For altered liver and kidney function tests, eligibility criteria can be reassessed at 24-96 hours, following the institution of adequate supportive measures.
* Presence of serious, active, uncontrolled infections.
* Pre-existing HIV positive serology (i.e. already known before enrolment). If HIV positivity is detected after enrolment, the patient is put off study.
* A history of cancer that is not in a remission phase following surgery and/or radiotherapy and/or chemotherapy, with a life expectancy \<1 year.
* Pregnancy declared by the patient, unless a decision is taken with the patient to induce a therapeutic abortion in order to carry on with the ALL therapy. A pregnancy test is performed at diagnosis, but does not preclude the enrolment into study. Fertile patients will be advised to adopt contraceptive methods while on treatment.

Primary outcomes:
measure: Number of patients that obtain a negative Minimal Residual Disease (MRD)
timeFrame: At week 14 from study entry
Secondary outcomes:
measure: Number of patients in complete remission (CR)
timeFrame: At 32 months from study entry
measure: Number of patients that reach disease-free survial
timeFrame: At 32 months from study entry
measure: Number of patients that relapse
timeFrame: At 32 months from study entry
measure: Number of patients that dye due to treatment
timeFrame: At 32 months from study entry
measure: Number of serious adverse events
timeFrame: At 32 months from study entry
Other outcomes:
Locations:
city: Ancona
country: Italy
facility: AOU Ospedali Riuniti Umberto I - G.M. LANCISI - G. SALESI
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: Bari
country: Italy
facility: UOC di Ematologia - Istituto Tumori - Giovanni Paolo II
city: Barletta
country: Italy
facility: UOC Ematologia Ospedale " Monsignor Raffaele Dimiccoli"
city: Bergamo
country: Italy
facility: Azienda Ospedaliera - Papa Giovanni XXIII
city: Bologna
country: Italy
facility: Istituto di Ematologia "Lorenzo e A. Seragnoli" - Policlinico S. Orsola - Malpighi
city: Bolzano
country: Italy
facility: Comprensorio Sanitario di Bolzano - Azienda Sanitaria dell'Alto Adige - Ematologia e Centro TMO - Ospedale S.Maurizio
city: Brescia
country: Italy
facility: Spedali Civili - Brescia - Azienda Ospedaliera - U.O. Ematologia
city: Brindisi
country: Italy
facility: Divisione di Ematologia Ospedale A. Perrino
city: Cagliari
country: Italy
facility: ASL N.8 - Ospedale "A. Businco" - Struttura Complessa di Ematologia e CTMO
city: Catania
country: Italy
facility: Università di Catania - Cattedra di Ematologia - Ospedale "Ferrarotto"
city: Cuneo
country: Italy
facility: S.C. Ematologia ASO S. Croce e Carle
city: Firenze
country: Italy
facility: Unità di Ricerca e di Malattie del sangue - Ematologia San Luca Vecchio
city: Genova
country: Italy
facility: IRCCS_AOU San Martino-IST-Ematologia 1-Monoblocco 11°piano- lato ponente
city: Latina
country: Italy
facility: UOC di Ematologia con trapianto Ospedale S. Maria Goretti
city: Lecce
country: Italy
facility: ASL Le/1 P.O. Vito Fazzi - U.O. di Ematologia ed UTIE
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnoli per lo Studio e la Cura dei Tumori- IRST
city: Messina
country: Italy
facility: A.O.U. - Policlinico G. Martino Messina Oncologia Medica - U.O.C. Ematologia
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
city: Milano
country: Italy
facility: Ospedale Niguarda " Ca Granda" - SC Ematologia
city: Milano
country: Italy
facility: U.O. Ematologia e Trapianto di MIdollo - Ist.Scientifico Ospedale San Raffaele
city: Modena
country: Italy
facility: UO Ematologia - AOU Policlinico di Modena
city: Napoli
country: Italy
facility: Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli"
city: Napoli
country: Italy
facility: Università degli Studi di Napoli "Federico II" - Facoltà di Medicina e Chirurgia
city: Novara
country: Italy
facility: S.C.D.U. Ematologia - Università del Piemonte Orientale Amedeo Avogadro
city: Nuoro
country: Italy
facility: U.O. CTMO Ematologia - Osp. S.Francesco
city: Orbassano
country: Italy
facility: S.C.D.U.Medicina Interna a indirizzo ematologico
city: Padova
country: Italy
facility: Università degli Studi di Padova - Ematologia ed Immunologia Clinica
city: Pagani
country: Italy
facility: Oncoematologia -plesso ospedaliero "A. Tortora" di Pagani
city: Palermo
country: Italy
facility: Ospedali Riuniti "Villa Sofia-Cervello"
city: Palermo
country: Italy
facility: U.O. di Ematologia con trapianto - Centro di Riferimento Regionale per le coagulopatie rare nel bambino e nell'adulto - A.U. Policlinico "Paolo Giaccone"
city: Parma
country: Italy
facility: Day Hospital dell'U.O.C di Ematologia e CTMO Padiglione 1
city: Pavia
country: Italy
facility: S.C. Ematologia - Fondazione IRCCS Policlinico S. Matteo
city: Perugia
country: Italy
facility: Sezione di Ematologia ed Immunologia Clinica - Ospedale S.Maria della Misericordia
city: Pescara
country: Italy
facility: U.O. Ematologia Clinica - Azienda USL di Pescara
city: Piacenza
country: Italy
facility: U.O. Ematologia - AUSL Ospedale G. da Saliceto
city: Ravenna
country: Italy
facility: Dipartimento Oncologico - Ospedale S.Maria delle Croci
city: Reggio Calabria
country: Italy
facility: Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli"
city: Rimini
country: Italy
facility: Ospedale "Infermi"
city: Roma
country: Italy
facility: Az. Ospedaliera "Sant' Andrea"-Università la Sapienza II Facoltà di Medicina e Chirurgia
city: Roma
country: Italy
facility: Complesso Ospedaliero S. Giovanni Addolorata
city: Roma
country: Italy
facility: Padiglione Cesalpino - I piano - Divisione di Ematologia - Ospedale S. Camillo
city: Roma
country: Italy
facility: S.C. di Ematologia e Trapianti - I.F.O. Istituto Nazionale Tumori Regina Elena
city: Roma
country: Italy
facility: U.O.C. Ematologia - Ospedale S. Eugenio
city: Roma
country: Italy
facility: Università Cattolica del Sacro Cuore - Policlinico A. Gemelli
city: Roma
country: Italy
facility: Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari - Divisione di Ematologia
city: Roma
country: Italy
facility: Università degli Studi - Policlinico di Tor Vergata
city: Rozzano
country: Italy
facility: Sezione di Ematologia Cancer Center Humanitas
city: Salerno
country: Italy
facility: UOC di Ematologia - AOU San Giovanni di Dio e Ruggi D'Aragona
city: San Giovanni Rotondo
country: Italy
facility: Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza
city: Siena
country: Italy
facility: U.O.C. Ematologia - A.O. Senese - Policlinico " Le Scotte"
city: Taranto
country: Italy
facility: U.O.C. di Ematologia - A.O. " SS Annunziata" - P.O. S.G. Moscati
city: Torino
country: Italy
facility: Divisione di Ematologia dell'Università di Torino - "Città della Salute e della Scienza"
city: Torino
country: Italy
facility: Ematologia e Terapie Cellulari- A.S.O. Ordine Mauriziano, P.O. Umberto I-Ospedale
city: Torino
country: Italy
facility: S.C. Ematologia 2 A.O. Città della Salute e della Scienza di Torino San Giovanni Battista
city: Trieste
country: Italy
facility: Struttura Complessa Ematologia - Azienda Ospedaliera Universitaria Integrata-Ospedale Maggiore
city: Udine
country: Italy
facility: Clinica Ematologica-Centro Trapianti e Terapie cellulari AOU,
city: Verona
country: Italy
facility: Istituti Ospitalieri di Verona- Div. di Ematologia - Policlinico G.B. Rossi
city: Vicenza
country: Italy
facility: ULSS N.6 Osp. S. Bortolo
Study officials:
affiliation: Azienda ULSS 12 "Veneziana" U.O. Ematologia Direttore Renato Bassan
name: Renato Bassan
role: STUDY_CHAIR
affiliation: Policlinico Umberto I, Hematology Department.
name: Roberto Foà
role: STUDY_DIRECTOR
affiliation: Ospedale di Bergamo
name: Alessandro Rambaldi
role: STUDY_DIRECTOR
References: