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

NCT ID: NCT03367299

Last Updated: 2025-01-22

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

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

149 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-06-08

Study Completion Date

2024-09-02

Brief Summary

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

Detailed Description

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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.

Conditions

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Acute Lymphoid Leukemia Philadelphia Chromosome-Negative B-Cell Precursor

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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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.

Group Type EXPERIMENTAL

Chemotherapy + Blinatumomab

Intervention Type DRUG

Chemotherapy cycles are administered at 21-28 days intervals and each blinatumomab course is 28-day long.

Interventions

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Chemotherapy + Blinatumomab

Chemotherapy cycles are administered at 21-28 days intervals and each blinatumomab course is 28-day long.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 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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Renato Bassan

Role: STUDY_CHAIR

Azienda ULSS 12 "Veneziana" U.O. Ematologia Direttore Renato Bassan

Roberto Foà

Role: STUDY_DIRECTOR

Policlinico Umberto I, Hematology Department.

Alessandro Rambaldi

Role: STUDY_DIRECTOR

Ospedale di Bergamo

Locations

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Clinica Ematologica-Centro Trapianti e Terapie cellulari AOU,

Udine, , Italy

Site Status

AOU Ospedali Riuniti Umberto I - G.M. LANCISI - G. SALESI

Ancona, , Italy

Site Status

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

Ascoli Piceno, , Italy

Site Status

Az.Ospedaliera S.G.Moscati

Avellino, , Italy

Site Status

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

Bari, , Italy

Site Status

UOC di Ematologia - Istituto Tumori - Giovanni Paolo II

Bari, , Italy

Site Status

UOC Ematologia Ospedale " Monsignor Raffaele Dimiccoli"

Barletta, , Italy

Site Status

Azienda Ospedaliera - Papa Giovanni XXIII

Bergamo, , Italy

Site Status

Istituto di Ematologia "Lorenzo e A. Seragnoli" - Policlinico S. Orsola - Malpighi

Bologna, , Italy

Site Status

Comprensorio Sanitario di Bolzano - Azienda Sanitaria dell'Alto Adige - Ematologia e Centro TMO - Ospedale S.Maurizio

Bolzano, , Italy

Site Status

Spedali Civili - Brescia - Azienda Ospedaliera - U.O. Ematologia

Brescia, , Italy

Site Status

Divisione di Ematologia Ospedale A. Perrino

Brindisi, , Italy

Site Status

ASL N.8 - Ospedale "A. Businco" - Struttura Complessa di Ematologia e CTMO

Cagliari, , Italy

Site Status

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

Catania, , Italy

Site Status

S.C. Ematologia ASO S. Croce e Carle

Cuneo, , Italy

Site Status

Unità di Ricerca e di Malattie del sangue - Ematologia San Luca Vecchio

Florence, , Italy

Site Status

IRCCS_AOU San Martino-IST-Ematologia 1-Monoblocco 11°piano- lato ponente

Genova, , Italy

Site Status

UOC di Ematologia con trapianto Ospedale S. Maria Goretti

Latina, , Italy

Site Status

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

Lecce, , Italy

Site Status

Istituto Scientifico Romagnoli per lo Studio e la Cura dei Tumori- IRST

Meldola, , Italy

Site Status

A.O.U. - Policlinico G. Martino Messina Oncologia Medica - U.O.C. Ematologia

Messina, , Italy

Site Status

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

Mestre, , Italy

Site Status

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico UOC Oncoematologia

Milan, , Italy

Site Status

Ospedale Niguarda " Ca Granda" - SC Ematologia

Milan, , Italy

Site Status

U.O. Ematologia e Trapianto di MIdollo - Ist.Scientifico Ospedale San Raffaele

Milan, , Italy

Site Status

UO Ematologia - AOU Policlinico di Modena

Modena, , Italy

Site Status

Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli"

Napoli, , Italy

Site Status

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

Napoli, , Italy

Site Status

S.C.D.U. Ematologia - Università del Piemonte Orientale Amedeo Avogadro

Novara, , Italy

Site Status

U.O. CTMO Ematologia - Osp. S.Francesco

Nuoro, , Italy

Site Status

S.C.D.U.Medicina Interna a indirizzo ematologico

Orbassano, , Italy

Site Status

Università degli Studi di Padova - Ematologia ed Immunologia Clinica

Padua, , Italy

Site Status

Oncoematologia -plesso ospedaliero "A. Tortora" di Pagani

Pagani, , Italy

Site Status

Ospedali Riuniti "Villa Sofia-Cervello"

Palermo, , Italy

Site Status

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

Site Status

Day Hospital dell'U.O.C di Ematologia e CTMO Padiglione 1

Parma, , Italy

Site Status

S.C. Ematologia - Fondazione IRCCS Policlinico S. Matteo

Pavia, , Italy

Site Status

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

Perugia, , Italy

Site Status

U.O. Ematologia Clinica - Azienda USL di Pescara

Pescara, , Italy

Site Status

U.O. Ematologia - AUSL Ospedale G. da Saliceto

Piacenza, , Italy

Site Status

Dipartimento Oncologico - Ospedale S.Maria delle Croci

Ravenna, , Italy

Site Status

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

Reggio Calabria, , Italy

Site Status

Ospedale "Infermi"

Rimini, , Italy

Site Status

Az. Ospedaliera "Sant' Andrea"-Università la Sapienza II Facoltà di Medicina e Chirurgia

Roma, , Italy

Site Status

Complesso Ospedaliero S. Giovanni Addolorata

Roma, , Italy

Site Status

Padiglione Cesalpino - I piano - Divisione di Ematologia - Ospedale S. Camillo

Roma, , Italy

Site Status

S.C. di Ematologia e Trapianti - I.F.O. Istituto Nazionale Tumori Regina Elena

Roma, , Italy

Site Status

U.O.C. Ematologia - Ospedale S. Eugenio

Roma, , Italy

Site Status

Università Cattolica del Sacro Cuore - Policlinico A. Gemelli

Roma, , Italy

Site Status

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

Roma, , Italy

Site Status

Università degli Studi - Policlinico di Tor Vergata

Roma, , Italy

Site Status

Sezione di Ematologia Cancer Center Humanitas

Rozzano, , Italy

Site Status

UOC di Ematologia - AOU San Giovanni di Dio e Ruggi D'Aragona

Salerno, , Italy

Site Status

Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, , Italy

Site Status

U.O.C. Ematologia - A.O. Senese - Policlinico " Le Scotte"

Siena, , Italy

Site Status

U.O.C. di Ematologia - A.O. " SS Annunziata" - P.O. S.G. Moscati

Taranto, , Italy

Site Status

Divisione di Ematologia dell'Università di Torino - "Città della Salute e della Scienza"

Torino, , Italy

Site Status

Ematologia e Terapie Cellulari- A.S.O. Ordine Mauriziano, P.O. Umberto I-Ospedale

Torino, , Italy

Site Status

S.C. Ematologia 2 A.O. Città della Salute e della Scienza di Torino San Giovanni Battista

Torino, , Italy

Site Status

Struttura Complessa Ematologia - Azienda Ospedaliera Universitaria Integrata-Ospedale Maggiore

Trieste, , Italy

Site Status

Istituti Ospitalieri di Verona- Div. di Ematologia - Policlinico G.B. Rossi

Verona, , Italy

Site Status

ULSS N.6 Osp. S. Bortolo

Vicenza, , Italy

Site Status

Countries

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Italy

References

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Bassan R, Chiaretti S, Della Starza I, Santoro A, Spinelli O, Tosi M, Elia L, Cardinali D, De Propris MS, Piccini M, Lussana F, Annunziata M, Chiusolo P, Zappasodi P, Borlenghi E, Leoncin M, Califano C, Bocchia M, Di Raimondo F, Grimaldi F, Tiribelli M, Candoni A, Lico A, Audisio E, Lunghi M, Mianulli AM, Di Trani M, Arena V, Messina M, Piciocchi A, Fazi P, Rambaldi A, Foa R. Up-front blinatumomab improves MRD clearance and outcome in adult Ph- B-lineage ALL: the GIMEMA LAL2317 phase 2 study. Blood. 2025 May 22;145(21):2447-2459. doi: 10.1182/blood.2024027500.

Reference Type DERIVED
PMID: 40009490 (View on PubMed)

Related Links

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http://www.gimema.it

GIMEMA Foundation website

Other Identifiers

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LAL2317

Identifier Type: -

Identifier Source: org_study_id

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