MRD/Risk-oriented Therapy of Adult Ph- ALL Including Pegylated Asparaginase and Lineage-targeted Methotrexate

NCT ID: NCT02067143

Last Updated: 2021-09-08

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

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

204 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-05-20

Study Completion Date

2020-12-07

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This study will be conducted in different centres and will study adult patients with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL). The study treatment will include a induction/consolidation therapy incorporating pegylated Asparaginase (Peg-ASP) and lineage-targeted high-dose methotrexate plus other antileukemic drugs, for the achievement of an early negative minimal residual disease (MRD) status. The MRD study supports a risk/MRD-oriented final consolidation phase.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

The aim of this clinical study in adult ALL is to improve , by risk category, the overall disease-free survival in relation to the achievement of an early MRD negative status and following induction/consolidation with Peg-ASP, lineage-targeted methotrexate infusions and other disease-specific therapeutic elements, with or without the application of allogeneic or autologous SCT depending on risk class and MRD study results. A survey of severe infections occurring along the entire chemotherapy and stem cell transplant program and until 2 years from the achievement of CR will be performed with the aim to increase the knowledge of these complications and to evaluate their impact on the antileukemic program and on the long term outcome of the underlying malignancy. The prospective survey of severe infections will be performed as an ancillary observational objective of the present study.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Untreated Philadelphia Positive Acute Lymphoblastic Leukemia De Novo Secondary Low-dose Corticosteroids Pretreatment

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Study population

In this phase II multicentric trial, eligible patients with Ph- ALL/LL will receive homogeneous supportive care and chemotherapy and will be homogeneously analyzed for response at prefixed timepoints from induction day 1. For risk-/MRD-oriented therapy, CR patients will be stratified by risk class according to diagnostic characteristics, MRD study and CT/PET (LL only) results during early consolidation.

Group Type EXPERIMENTAL

Prephase PDN + CY

Intervention Type DRUG

Cycle 1 Induction

Intervention Type DRUG

Cycle 2 Induction / Early consolidation

Intervention Type DRUG

Cycle 3 Early consolidation

Intervention Type DRUG

Cycle 4 Consolidation

Intervention Type DRUG

Cycle 5 Consolidation

Intervention Type DRUG

Cycle 6 Consolidation

Intervention Type DRUG

Cycle 7 Consolidation

Intervention Type DRUG

Cycle 8 Reinduction

Intervention Type DRUG

Maintenance

Intervention Type DRUG

If MRD negative MRD u/k SR

Allogeneic SCT or Autologous SCT

Intervention Type PROCEDURE

If MRD positive MRD u/k HR

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Prephase PDN + CY

Intervention Type DRUG

Cycle 1 Induction

Intervention Type DRUG

Cycle 2 Induction / Early consolidation

Intervention Type DRUG

Cycle 3 Early consolidation

Intervention Type DRUG

Cycle 4 Consolidation

Intervention Type DRUG

Cycle 5 Consolidation

Intervention Type DRUG

Cycle 6 Consolidation

Intervention Type DRUG

Cycle 7 Consolidation

Intervention Type DRUG

Cycle 8 Reinduction

Intervention Type DRUG

Maintenance

If MRD negative MRD u/k SR

Intervention Type DRUG

Allogeneic SCT or Autologous SCT

If MRD positive MRD u/k HR

Intervention Type PROCEDURE

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

VCR + IDR + DXM + ASP + IT IDR + CY + ARA-C + ASP + 6MP + DXM + IT MTX + ARA-C VCR + IDR + CY + ARA-C + 6-MP + DXM + IT MTX + ASP + 6-MP VCR + IDR + CY + ARA-C + ASP + 6MP + DXM + IT MTX + ARA-C VCR + IDR + DXM + PDN + CY + IT CY or VP and 6MP/MTX + 12 cycles of 6MP/MTX + Maintenance

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Signed written informed consent according to ICH/EU/GCP and national local laws.
* Age 18-65 years.
* A diagnosis of untreated Ph- ALL or LL is required, either de novo or secondary to chemo-radiotherapy for other cancer. Pretreatment with low-dose corticosteroids in patients presenting with hyperleukocytosis is allowed. All diagnostic procedures need to be performed on freshly obtained bone marrow (BM) and peripheral blood (PB) samples. The diagnosis must be one of: de novo ALL, secondary ALL, B-/T-cell LL Full cytological, cytochemical, cytogenetic and immunobiological disease characterization according to EGIL and WHO classifications. Bone marrow and peripheral blood sampling (ALL) or biopsy specimen (LL) are required for MRD study. Detailed indications on patient registration, storage of representative diagnostic material and diagnostic work-up, including the forwarding of samples for MRD study are given in Appendix B.
* Bone marrow and peripheral blood sampling (ALL) or biopsy specimen (LL) for MRD study.
* ECOG performance status 0-2, unless a performance of 3 is unequivocally caused by the disease itself and not by preexisting comorbidity, and is considered and/or documented to be reversible following the application of antileukemic therapy and appropriate supportive measures.

Exclusion Criteria

* Diagnosis of Burkitt's leukemia or lymphoma.
* Down's syndrome
* 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.
* Pre-existing HIV positive serology (i.e. already known before enrolment). If HIV positivity is detected after enrolment, the patient is sent off study.
* A history of cancer that is not in a remission phase following surgery and/or radiotherapy and/or chemotherapy, with life expectancy \<1 year.
* Pregnancy declared by the patient herself, unless a decision is taken with the patient to induce a therapeutic abortion in order to carry on with 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

Meet the organizations funding or collaborating on the study and learn about their roles.

Gruppo Italiano Malattie EMatologiche dell'Adulto

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Renato Bassan, Pr.

Role: STUDY_CHAIR

Azienda ULSS 12 Veneziana

Roberto Foà, Pr.

Role: STUDY_DIRECTOR

Policlinico Umberto I, Hematology Department.

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

S.O.C. di Ematologia - Azienda Ospedaliera - SS. Antonio e Biagio e Cesare Arrigo

Alessandria, , Italy

Site Status

Azienda Ospedaliero - Universitaria 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

Azienda Ospedaliera - Papa Giovanni XXIII

Bergamo, , Italy

Site Status

Istituto di Ematologia "Lorenzo e A. Seragnoli" - Università degli Studi di Bologna - 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

Ao Brotzu, Presidio Ospedaliero A. Businco - Cagliari - Sc Ematologia E Ctmo

Cagliari, , Italy

Site Status

CTMO - Ematologia - Ospedale "Binaghi"

Cagliari, , Italy

Site Status

Unità Operativa Complessa di Onco-Ematologia - A.O. S.Anna e S.Sebastiano

Caserta, , Italy

Site Status

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

Catania, , Italy

Site Status

Unità Operativa Complessa di Ematologia - Arcispedale S. Maria Nuova

Cona, , Italy

Site Status

Sezione di Ematologia C.T.M.O. Istituti Ospitalieri

Cremona, , Italy

Site Status

S.C. Ematologia ASO S. Croce e Carle

Cuneo, , Italy

Site Status

IRCCS_AOU San Martino-IST.Clinica Ematologica

Genova, , Italy

Site Status

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

Lecce, , Italy

Site Status

Divisione di Ematologia - Azienda Ospedaliera Ospedali Riuniti "Papardo Piemonte" P.O. Papardo

Messina, , Italy

Site Status

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

Mestre, , Italy

Site Status

Fondazione Irccs Ca' Granda, Ospedale Maggiore Policlinico - Milano - Ematologia - Padiglione Marcora

Milan, , Italy

Site Status

Ospedale Niguarda " Ca Granda" - SC Ematologia Blocco SUD, Ponti Est, Scala E, 4° piano

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 "S.Gerardo"

Monza, , Italy

Site Status

Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli"

Napoli, , Italy

Site Status

S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro

Novara, , Italy

Site Status

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

Nuoro, , Italy

Site Status

Dip. di Scienze Cliniche e Biologiche - Ospedale S. Luigi Gonzaga-Medicina Interna 2

Orbassano, , Italy

Site Status

Università degli Studi di Padova - Ematologia ed Immunologia Clinica

Padua, , 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 Dipart. Biomedico di Medicina Interna - A.U. Policlinico "Paolo Giaccone"

Palermo, , Italy

Site Status

Casa Di Cura La Maddalena S.P.A. - Dipartimento Oncologico Di Iii Livello - Palermo - Uo Oncoematologia E Tmo

Palmero, , Italy

Site Status

Day Hospital dell'U.O.C di Ematologia e CTMO Padiglione 1 TORRE DELLE MEDICINE, 6° piano

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

Div. di Ematologia di Muraglia - CTMO Ospedale San Salvatore

Pesaro, , Italy

Site Status

U.O. Ematologia Clinica - Azienda USL di Pescara

Pescara, , Italy

Site Status

Unità Operativa Ematologia e Centro Trapianti - Dipartimento di Oncologia ed Ematologia - AUSL Ospedale G. da Saliceto

Piacenza, , Italy

Site Status

Università di Pisa - Azienda Ospedaliera Pisana - Dipartimento di Oncologia, dei Trapianti e delle nuove Tecnologie in Medicina - Divisione di Ematologia

Pisa, , Italy

Site Status

Ematologia - Ospedale San Carlo

Potenza, , 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

Unità Operativa Complessa di Ematologia - Arcispedale S. Maria Nuova

Reggio Emilia, , Italy

Site Status

Ospedale "Infermi"

Rimini, , Italy

Site Status

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

Roma, , Italy

Site Status

Complesso Ospedaliero S. Giovanni Addolorata

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

Roma, , Italy

Site Status

Sezione di Ematologia Cancer Center Humanitas

Rozzano, , Italy

Site Status

UOC di Ematologia e Trapianti di Cellule Staminali Emopoietiche - 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 e Trapianti - A.O. Senese - Policlinico " Le Scotte"

Siena, , Italy

Site Status

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

Torino, , Italy

Site Status

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

Torino, , Italy

Site Status

Ospedale Mauriziano Umberto I - Torino - Scdu Ematologia

Torino, , Italy

Site Status

U.L.S.S. 9 UOC Ematologia - Ospedale Ca' Foncello

Treviso, , Italy

Site Status

Clinica Ematologica-Centro Trapianti e Terapie cellulari Azienda Ospedaliero-Universitaria, Udine

Udine, , Italy

Site Status

Università degli Studi di Verona - A. O. - Istituti Ospitalieri di Verona- Div. di Ematologia - Policlinico G.B. Rossi

Verona, , Italy

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Italy

References

Explore related publications, articles, or registry entries linked to this study.

Bassan R, Chiaretti S, Della Starza I, Spinelli O, Santoro A, Paoloni F, Messina M, Elia L, De Propris MS, Scattolin AM, Audisio E, Marbello L, Borlenghi E, Zappasodi P, Mauro E, Martinelli G, Mattei D, Fracchiolla N, Bocchia M, De Fabritiis P, Bonifacio M, Candoni A, Cassibba V, Di Bartolomeo P, Latte G, Trappolini S, Guarini A, Vitale A, Fazi P, Piciocchi A, Rambaldi A, Foa R. Pegaspargase-modified risk-oriented program for adult acute lymphoblastic leukemia: results of the GIMEMA LAL1913 trial. Blood Adv. 2023 Aug 22;7(16):4448-4461. doi: 10.1182/bloodadvances.2022009596.

Reference Type DERIVED
PMID: 37276451 (View on PubMed)

Piciocchi A, Messina M, Elia L, Vitale A, Soddu S, Testi AM, Chiaretti S, Mancini M, Albano F, Spadano A, Krampera M, Bonifacio M, Cairoli R, Vetro C, Colella F, Ferrara F, Cimino G, Bassan R, Fazi P, Vignetti M. Prognostic impact of KMT2A-AFF1-positivity in 926 BCR-ABL1-negative B-lineage acute lymphoblastic leukemia patients treated in GIMEMA clinical trials since 1996. Am J Hematol. 2021 Sep 1;96(9):E334-E338. doi: 10.1002/ajh.26253. Epub 2021 Jun 9. No abstract available.

Reference Type DERIVED
PMID: 34048072 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

http://www.gimema.it

GIMEMA Foundation

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

LAL1913

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.