Sequential Chemotherapy and Blinatumomab to Improve MRD Response and Survival in Acute Lymphoblastic Leukemia
- Conditions
- Philadelphia Chromosome-Negative B-Cell PrecursorAcute Lymphoid Leukemia
- Interventions
- Drug: Chemotherapy + Blinatumomab
- Registration Number
- NCT03367299
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 149
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Chemotherapy + Blinatumomab Chemotherapy + Blinatumomab Treatment sequence consists of eight chemotherapy courses and two blinatumomab courses. Patients not in CR after chemotherapy course 2 will go off-study.
- Primary Outcome Measures
Name Time Method Number of patients that obtain a negative Minimal Residual Disease (MRD) At week 14 from study entry
- Secondary Outcome Measures
Name Time Method Number of patients that dye due to treatment At 32 months from study entry Treatment-related mortality
Number of patients that reach disease-free survial At 32 months from study entry Number of patients in complete remission (CR) At 32 months from study entry Number of patients that relapse At 32 months from study entry Number of serious adverse events At 32 months from study entry Safety
Trial Locations
- Locations (62)
UO Ematologia con trapianto-Università degli Studi di Bari Aldo Moro
🇮🇹Bari, Italy
Azienda Ospedaliera - Papa Giovanni XXIII
🇮🇹Bergamo, Italy
UOC di Ematologia - Istituto Tumori - Giovanni Paolo II
🇮🇹Bari, Italy
Istituto di Ematologia "Lorenzo e A. Seragnoli" - Policlinico S. Orsola - Malpighi
🇮🇹Bologna, Italy
Spedali Civili - Brescia - Azienda Ospedaliera - U.O. Ematologia
🇮🇹Brescia, Italy
Divisione di Ematologia Ospedale A. Perrino
🇮🇹Brindisi, Italy
S.C. Ematologia ASO S. Croce e Carle
🇮🇹Cuneo, Italy
IRCCS_AOU San Martino-IST-Ematologia 1-Monoblocco 11°piano- lato ponente
🇮🇹Genova, Italy
UOC di Ematologia con trapianto Ospedale S. Maria Goretti
🇮🇹Latina, Italy
U.O. di Ematologia- Ospedale dell'Angelo - Mestre
🇮🇹Mestre, Italy
Ospedale Niguarda " Ca Granda" - SC Ematologia
🇮🇹Milano, Italy
U.O. Ematologia e Trapianto di MIdollo - Ist.Scientifico Ospedale San Raffaele
🇮🇹Milano, Italy
UO Ematologia - AOU Policlinico di Modena
🇮🇹Modena, Italy
Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli"
🇮🇹Napoli, Italy
Università degli Studi di Napoli "Federico II" - Facoltà di Medicina e Chirurgia
🇮🇹Napoli, Italy
S.C.D.U. Ematologia - Università del Piemonte Orientale Amedeo Avogadro
🇮🇹Novara, Italy
U.O. CTMO Ematologia - Osp. S.Francesco
🇮🇹Nuoro, Italy
S.C.D.U.Medicina Interna a indirizzo ematologico
🇮🇹Orbassano, Italy
Oncoematologia -plesso ospedaliero "A. Tortora" di Pagani
🇮🇹Pagani, Italy
Ospedali Riuniti "Villa Sofia-Cervello"
🇮🇹Palermo, Italy
U.O. di Ematologia con trapianto - Centro di Riferimento Regionale per le coagulopatie rare nel bambino e nell'adulto - A.U. Policlinico "Paolo Giaccone"
🇮🇹Palermo, Italy
Day Hospital dell'U.O.C di Ematologia e CTMO Padiglione 1
🇮🇹Parma, Italy
S.C. Ematologia - Fondazione IRCCS Policlinico S. Matteo
🇮🇹Pavia, Italy
Sezione di Ematologia ed Immunologia Clinica - Ospedale S.Maria della Misericordia
🇮🇹Perugia, Italy
U.O. Ematologia - AUSL Ospedale G. da Saliceto
🇮🇹Piacenza, Italy
Dipartimento Oncologico - Ospedale S.Maria delle Croci
🇮🇹Ravenna, Italy
Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli"
🇮🇹Reggio Calabria, Italy
Ospedale "Infermi"
🇮🇹Rimini, Italy
Az. Ospedaliera "Sant' Andrea"-Università la Sapienza II Facoltà di Medicina e Chirurgia
🇮🇹Roma, Italy
Complesso Ospedaliero S. Giovanni Addolorata
🇮🇹Roma, Italy
Padiglione Cesalpino - I piano - Divisione di Ematologia - Ospedale S. Camillo
🇮🇹Roma, Italy
S.C. di Ematologia e Trapianti - I.F.O. Istituto Nazionale Tumori Regina Elena
🇮🇹Roma, Italy
U.O.C. Ematologia - Ospedale S. Eugenio
🇮🇹Roma, Italy
Università Cattolica del Sacro Cuore - Policlinico A. Gemelli
🇮🇹Roma, Italy
Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari - Divisione di Ematologia
🇮🇹Roma, Italy
Sezione di Ematologia Cancer Center Humanitas
🇮🇹Rozzano, Italy
Divisione di Ematologia dell'Università di Torino - "Città della Salute e della Scienza"
🇮🇹Torino, Italy
Università degli Studi - Policlinico di Tor Vergata
🇮🇹Roma, Italy
Comprensorio Sanitario di Bolzano - Azienda Sanitaria dell'Alto Adige - Ematologia e Centro TMO - Ospedale S.Maurizio
🇮🇹Bolzano, Italy
UOC Ematologia Ospedale " Monsignor Raffaele Dimiccoli"
🇮🇹Barletta, Italy
ASL Le/1 P.O. Vito Fazzi - U.O. di Ematologia ed UTIE
🇮🇹Lecce, Italy
Istituto Scientifico Romagnoli per lo Studio e la Cura dei Tumori- IRST
🇮🇹Meldola, Italy
A.O.U. - Policlinico G. Martino Messina Oncologia Medica - U.O.C. Ematologia
🇮🇹Messina, Italy
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico UOC Oncoematologia
🇮🇹Milano, Italy
Ematologia e Terapie Cellulari- A.S.O. Ordine Mauriziano, P.O. Umberto I-Ospedale
🇮🇹Torino, Italy
Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza
🇮🇹San Giovanni Rotondo, Italy
S.C. Ematologia 2 A.O. Città della Salute e della Scienza di Torino San Giovanni Battista
🇮🇹Torino, Italy
Struttura Complessa Ematologia - Azienda Ospedaliera Universitaria Integrata-Ospedale Maggiore
🇮🇹Trieste, Italy
Clinica Ematologica-Centro Trapianti e Terapie cellulari AOU,
🇮🇹Udine, Italy
Istituti Ospitalieri di Verona- Div. di Ematologia - Policlinico G.B. Rossi
🇮🇹Verona, Italy
Az.Ospedaliera S.G.Moscati
🇮🇹Avellino, Italy
AOU Ospedali Riuniti Umberto I - G.M. LANCISI - G. SALESI
🇮🇹Ancona, Italy
U.O.C. Ematologia e Terapia Cellulare - Ospedale "C. e G. Mazzoni" di Ascoli Piceno
🇮🇹Ascoli Piceno, Italy
ASL N.8 - Ospedale "A. Businco" - Struttura Complessa di Ematologia e CTMO
🇮🇹Cagliari, Italy
Università di Catania - Cattedra di Ematologia - Ospedale "Ferrarotto"
🇮🇹Catania, Italy
Unità di Ricerca e di Malattie del sangue - Ematologia San Luca Vecchio
🇮🇹Firenze, Italy
Università degli Studi di Padova - Ematologia ed Immunologia Clinica
🇮🇹Padova, Italy
U.O. Ematologia Clinica - Azienda USL di Pescara
🇮🇹Pescara, Italy
UOC di Ematologia - AOU San Giovanni di Dio e Ruggi D'Aragona
🇮🇹Salerno, Italy
U.O.C. Ematologia - A.O. Senese - Policlinico " Le Scotte"
🇮🇹Siena, Italy
U.O.C. di Ematologia - A.O. " SS Annunziata" - P.O. S.G. Moscati
🇮🇹Taranto, Italy
ULSS N.6 Osp. S. Bortolo
🇮🇹Vicenza, Italy