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

NCT03367299 | Completed Phase 2 FDA Drug

• 1 other identifier: LAL2317
• Study Type: interventional
• Target: 149
• Locations: 1 country
• Sites: 62

Brief Summary

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

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

Outcome Measures

Primary Outcomes (1)

• Number of patients that obtain a negative Minimal Residual Disease (MRD)

  At week 14 from study entry

Secondary Outcomes (5)

• Number of patients in complete remission (CR)

  At 32 months from study entry

• Number of patients that reach disease-free survial

  At 32 months from study entry

• Number of patients that relapse

  At 32 months from study entry

• Number of patients that dye due to treatment

  At 32 months from study entry

• Number of serious adverse events

  At 32 months from study entry

Study Arms (1)

Chemotherapy + Blinatumomab

EXPERIMENTAL

Treatment sequence consists of eight chemotherapy courses and two blinatumomab courses. Patients not in CR after chemotherapy course 2 will go off-study.

Drug: Chemotherapy + Blinatumomab

Interventions

Chemotherapy + Blinatumomab DRUG

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

Chemotherapy + Blinatumomab

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gruppo Italiano Malattie EMatologiche dell'Adulto: lead

Study Sites (62)

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

Ancona, Italy

Location

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

Ascoli Piceno, Italy

Location

Az.Ospedaliera S.G.Moscati

Avellino, Italy

Location

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

Bari, Italy

Location

UOC di Ematologia - Istituto Tumori - Giovanni Paolo II

Bari, Italy

Location

UOC Ematologia Ospedale " Monsignor Raffaele Dimiccoli"

Barletta, Italy

Location

Azienda Ospedaliera - Papa Giovanni XXIII

Bergamo, Italy

Location

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

Bologna, Italy

Location

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

Bolzano, Italy

Location

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

Brescia, Italy

Location

Divisione di Ematologia Ospedale A. Perrino

Brindisi, Italy

Location

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

Cagliari, Italy

Location

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

Catania, Italy

Location

S.C. Ematologia ASO S. Croce e Carle

Cuneo, Italy

Location

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

Florence, Italy

Location

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

Genova, Italy

Location

UOC di Ematologia con trapianto Ospedale S. Maria Goretti

Latina, Italy

Location

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

Lecce, Italy

Location

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

Meldola, Italy

Location

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

Messina, Italy

Location

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

Mestre, Italy

Location

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico UOC Oncoematologia

Milan, Italy

Location

Ospedale Niguarda " Ca Granda" - SC Ematologia

Milan, Italy

Location

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

Milan, Italy

Location

UO Ematologia - AOU Policlinico di Modena

Modena, Italy

Location

Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli"

Napoli, Italy

Location

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

Napoli, Italy

Location

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

Novara, Italy

Location

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

Nuoro, Italy

Location

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

Orbassano, Italy

Location

Università degli Studi di Padova - Ematologia ed Immunologia Clinica

Padua, Italy

Location

Oncoematologia -plesso ospedaliero "A. Tortora" di Pagani

Pagani, Italy

Location

Ospedali Riuniti "Villa Sofia-Cervello"

Palermo, Italy

Location

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

Location

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

Parma, Italy

Location

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

Pavia, Italy

Location

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

Perugia, Italy

Location

U.O. Ematologia Clinica - Azienda USL di Pescara

Pescara, Italy

Location

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

Piacenza, Italy

Location

Dipartimento Oncologico - Ospedale S.Maria delle Croci

Ravenna, Italy

Location

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

Reggio Calabria, Italy

Location

Ospedale "Infermi"

Rimini, Italy

Location

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

Roma, Italy

Location

Complesso Ospedaliero S. Giovanni Addolorata

Roma, Italy

Location

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

Roma, Italy

Location

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

Roma, Italy

Location

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

Roma, Italy

Location

Università Cattolica del Sacro Cuore - Policlinico A. Gemelli

Roma, Italy

Location

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

Roma, Italy

Location

Università degli Studi - Policlinico di Tor Vergata

Roma, Italy

Location

Sezione di Ematologia Cancer Center Humanitas

Rozzano, Italy

Location

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

Salerno, Italy

Location

Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, Italy

Location

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

Siena, Italy

Location

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

Taranto, Italy

Location

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

Torino, Italy

Location

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

Torino, Italy

Location

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

Torino, Italy

Location

Struttura Complessa Ematologia - Azienda Ospedaliera Universitaria Integrata-Ospedale Maggiore

Trieste, Italy

Location

Clinica Ematologica-Centro Trapianti e Terapie cellulari AOU,

Udine, Italy

Location

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

Verona, Italy

Location

ULSS N.6 Osp. S. Bortolo

Vicenza, Italy

Location

Related Publications (1)

• 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.

  PMID: 40009490 DERIVED

Related Links

• GIMEMA Foundation website

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Neoplasm, Residual

Interventions

Drug Therapy; blinatumomab

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Renato Bassan

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

  STUDY CHAIR

• Roberto Foà

  Policlinico Umberto I, Hematology Department.

  STUDY DIRECTOR

• Alessandro Rambaldi

  Ospedale di Bergamo

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2017
• First Posted: December 8, 2017
• Study Start: June 8, 2018
• Primary Completion: September 2, 2024
• Study Completion: September 2, 2024
• Last Updated: January 22, 2025

Record last verified: 2025-01

Locations

IT (62)