Sequential Chemotherapy and Blinatumomab to Improve MRD Response and Survival in Acute Lymphoblastic Leukemia

Acute Lymphoid Leukemia Clinical Trial

— LAL2317  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03367299
• Other study ID #: LAL2317
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 8, 2018
• Est. completion date: February 2024

Study information

• Verified date: January 2022
• Source: Gruppo Italiano Malattie EMatologiche dell'Adulto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 149
• Est. completion date: February 2024
• Est. primary completion date: February 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lymphoid Leukemia
• Leukemia
• Leukemia, Lymphoid
• Philadelphia Chromosome
• Philadelphia Chromosome-Negative B-Cell Precursor
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Chemotherapy + Blinatumomab
Chemotherapy cycles are administered at 21-28 days intervals and each blinatumomab course is 28-day long.

Locations

Country	Name	City	State
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	Az.Ospedaliera S.G.Moscati	Avellino
Italy	UO Ematologia con trapianto-Università degli Studi di Bari Aldo Moro	Bari
Italy	UOC di Ematologia - Istituto Tumori - Giovanni Paolo II	Bari
Italy	UOC Ematologia Ospedale " Monsignor Raffaele Dimiccoli"	Barletta
Italy	Azienda Ospedaliera - Papa Giovanni XXIII	Bergamo
Italy	Istituto di Ematologia "Lorenzo e A. Seragnoli" - Policlinico S. Orsola - Malpighi	Bologna
Italy	Comprensorio Sanitario di Bolzano - Azienda Sanitaria dell'Alto Adige - Ematologia e Centro TMO - Ospedale S.Maurizio	Bolzano
Italy	Spedali Civili - Brescia - Azienda Ospedaliera - U.O. Ematologia	Brescia
Italy	Divisione di Ematologia Ospedale A. Perrino	Brindisi
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	S.C. Ematologia ASO S. Croce e Carle	Cuneo
Italy	Unità di Ricerca e di Malattie del sangue - Ematologia San Luca Vecchio	Firenze
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	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	U.O. di Ematologia- Ospedale dell'Angelo - Mestre	Mestre
Italy	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico UOC Oncoematologia	Milano
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	Università degli Studi di Padova - Ematologia ed Immunologia Clinica	Padova
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 Clinica - Azienda USL di Pescara	Pescara
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	Università degli Studi - Policlinico di Tor Vergata	Roma
Italy	Sezione di Ematologia Cancer Center Humanitas	Rozzano
Italy	UOC di Ematologia - AOU San Giovanni di Dio e Ruggi D'Aragona	Salerno
Italy	Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza	San Giovanni Rotondo
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	Divisione di Ematologia dell'Università di Torino - "Città della Salute e della Scienza"	Torino
Italy	Ematologia e Terapie Cellulari- A.S.O. Ordine Mauriziano, P.O. Umberto I-Ospedale	Torino
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	ULSS N.6 Osp. S. Bortolo	Vicenza

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 that obtain a negative Minimal Residual Disease (MRD)		At week 14 from study entry
Secondary	Number of patients in complete remission (CR)		At 32 months from study entry
Secondary	Number of patients that reach disease-free survial		At 32 months from study entry
Secondary	Number of patients that relapse		At 32 months from study entry
Secondary	Number of patients that dye due to treatment	Treatment-related mortality	At 32 months from study entry
Secondary	Number of serious adverse events	Safety	At 32 months from study entry

External Links

•   GIMEMA Foundation website