Sequential Chemotherapy and Blinatumomab to Improve MRD Response and Survival in Acute Lymphoblastic Leukemia (LAL2317)

January 21, 2025 updated by: Gruppo Italiano Malattie EMatologiche dell'Adulto

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

149

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Ancona, Italy
        • AOU Ospedali Riuniti Umberto I - G.M. LANCISI - G. SALESI
      • Ascoli Piceno, Italy
        • U.O.C. Ematologia e Terapia Cellulare - Ospedale "C. e G. Mazzoni" di Ascoli Piceno
      • Avellino, Italy
        • Az.Ospedaliera S.G.Moscati
      • Bari, Italy
        • UO Ematologia con trapianto-Università degli Studi di Bari Aldo Moro
      • Bari, Italy
        • UOC di Ematologia - Istituto Tumori - Giovanni Paolo II
      • Barletta, Italy
        • UOC Ematologia Ospedale " Monsignor Raffaele Dimiccoli"
      • Bergamo, Italy
        • Azienda Ospedaliera - Papa Giovanni XXIII
      • Bologna, Italy
        • Istituto di Ematologia "Lorenzo e A. Seragnoli" - Policlinico S. Orsola - Malpighi
      • Bolzano, Italy
        • Comprensorio Sanitario di Bolzano - Azienda Sanitaria dell'Alto Adige - Ematologia e Centro TMO - Ospedale S.Maurizio
      • Brescia, Italy
        • Spedali Civili - Brescia - Azienda Ospedaliera - U.O. Ematologia
      • Brindisi, Italy
        • Divisione di Ematologia Ospedale A. Perrino
      • Cagliari, Italy
        • ASL N.8 - Ospedale "A. Businco" - Struttura Complessa di Ematologia e CTMO
      • Catania, Italy
        • Università di Catania - Cattedra di Ematologia - Ospedale "Ferrarotto"
      • Cuneo, Italy
        • S.C. Ematologia ASO S. Croce e Carle
      • Firenze, Italy
        • Unità di Ricerca e di Malattie del sangue - Ematologia San Luca Vecchio
      • Genova, Italy
        • IRCCS_AOU San Martino-IST-Ematologia 1-Monoblocco 11°piano- lato ponente
      • Latina, Italy
        • UOC di Ematologia con trapianto Ospedale S. Maria Goretti
      • Lecce, Italy
        • ASL Le/1 P.O. Vito Fazzi - U.O. di Ematologia ed UTIE
      • Meldola, Italy
        • Istituto Scientifico Romagnoli per lo Studio e la Cura dei Tumori- IRST
      • Messina, Italy
        • A.O.U. - Policlinico G. Martino Messina Oncologia Medica - U.O.C. Ematologia
      • Mestre, Italy
        • U.O. di Ematologia- Ospedale dell'Angelo - Mestre
      • Milano, Italy
        • U.O. Ematologia e Trapianto di MIdollo - Ist.Scientifico Ospedale San Raffaele
      • Milano, Italy
        • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico UOC Oncoematologia
      • Milano, Italy
        • Ospedale Niguarda " Ca Granda" - SC Ematologia
      • Modena, Italy
        • UO Ematologia - AOU Policlinico di Modena
      • Napoli, Italy
        • Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli"
      • Napoli, Italy
        • Università degli Studi di Napoli "Federico II" - Facoltà di Medicina e Chirurgia
      • Novara, Italy
        • S.C.D.U. Ematologia - Università del Piemonte Orientale Amedeo Avogadro
      • Nuoro, Italy
        • U.O. CTMO Ematologia - Osp. S.Francesco
      • Orbassano, Italy
        • S.C.D.U.Medicina Interna a indirizzo ematologico
      • Padova, Italy
        • Università degli Studi di Padova - Ematologia ed Immunologia Clinica
      • Pagani, Italy
        • Oncoematologia -plesso ospedaliero "A. Tortora" di Pagani
      • Palermo, 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"
      • Parma, Italy
        • Day Hospital dell'U.O.C di Ematologia e CTMO Padiglione 1
      • Pavia, Italy
        • S.C. Ematologia - Fondazione IRCCS Policlinico S. Matteo
      • Perugia, Italy
        • Sezione di Ematologia ed Immunologia Clinica - Ospedale S.Maria della Misericordia
      • Pescara, Italy
        • U.O. Ematologia Clinica - Azienda USL di Pescara
      • Piacenza, Italy
        • U.O. Ematologia - AUSL Ospedale G. da Saliceto
      • Ravenna, Italy
        • Dipartimento Oncologico - Ospedale S.Maria delle Croci
      • Reggio Calabria, Italy
        • Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli"
      • Rimini, Italy
        • Ospedale "Infermi"
      • Roma, Italy
        • Complesso Ospedaliero S. Giovanni Addolorata
      • Roma, Italy
        • Università Cattolica del Sacro Cuore - Policlinico A. Gemelli
      • Roma, Italy
        • S.C. di Ematologia e Trapianti - I.F.O. Istituto Nazionale Tumori Regina Elena
      • Roma, Italy
        • Università degli Studi - Policlinico di Tor Vergata
      • Roma, Italy
        • Padiglione Cesalpino - I piano - Divisione di Ematologia - Ospedale S. Camillo
      • Roma, Italy
        • Az. Ospedaliera "Sant' Andrea"-Università la Sapienza II Facoltà di Medicina e Chirurgia
      • Roma, Italy
        • U.O.C. Ematologia - Ospedale S. Eugenio
      • Roma, Italy
        • Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari - Divisione di Ematologia
      • Rozzano, Italy
        • Sezione di Ematologia Cancer Center Humanitas
      • Salerno, Italy
        • UOC di Ematologia - AOU San Giovanni di Dio e Ruggi D'Aragona
      • San Giovanni Rotondo, Italy
        • Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza
      • Siena, Italy
        • U.O.C. Ematologia - A.O. Senese - Policlinico " Le Scotte"
      • Taranto, Italy
        • U.O.C. di Ematologia - A.O. " SS Annunziata" - P.O. S.G. Moscati
      • Torino, Italy
        • S.C. Ematologia 2 A.O. Città della Salute e della Scienza di Torino San Giovanni Battista
      • Torino, 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
      • Trieste, Italy
        • Struttura Complessa Ematologia - Azienda Ospedaliera Universitaria Integrata-Ospedale Maggiore
      • Udine, Italy
        • Clinica Ematologica-Centro Trapianti e Terapie cellulari AOU,
      • Verona, Italy
        • Istituti Ospitalieri di Verona- Div. di Ematologia - Policlinico G.B. Rossi
      • Vicenza, Italy
        • ULSS N.6 Osp. S. Bortolo

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: Chemotherapy + Blinatumomab
Chemotherapy cycles are administered at 21-28 days intervals and each blinatumomab course is 28-day long.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of patients that obtain a negative Minimal Residual Disease (MRD)
Time Frame: At week 14 from study entry
At week 14 from study entry

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients in complete remission (CR)
Time Frame: At 32 months from study entry
At 32 months from study entry
Number of patients that reach disease-free survial
Time Frame: At 32 months from study entry
At 32 months from study entry
Number of patients that relapse
Time Frame: At 32 months from study entry
At 32 months from study entry
Number of patients that dye due to treatment
Time Frame: At 32 months from study entry
Treatment-related mortality
At 32 months from study entry
Number of serious adverse events
Time Frame: At 32 months from study entry
Safety
At 32 months from study entry

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gruppo Italiano Malattie EMatologiche dell'Adulto

Investigators

  • Study Chair: Renato Bassan, Azienda ULSS 12 "Veneziana" U.O. Ematologia Direttore Renato Bassan
  • Study Director: Roberto Foà, Policlinico Umberto I, Hematology Department.
  • Study Director: Alessandro Rambaldi, Ospedale di Bergamo

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 8, 2018

Primary Completion (Actual)

September 2, 2024

Study Completion (Actual)

September 2, 2024

Study Registration Dates

First Submitted

December 5, 2017

First Submitted That Met QC Criteria

December 5, 2017

First Posted (Actual)

December 8, 2017

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

January 21, 2025

Last Verified

January 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LAL2317

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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