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

NCT02067143 | Completed Phase 2

• 1 other identifier: LAL1913
• Study Type: interventional
• Target: 204
• Locations: 1 country
• Sites: 61

Brief Summary

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.

Conditions

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

Keywords

Untreated philadelphia positive acute lymphoblastic leukemia; De novo; Secondary; Low-dose corticosteroids pretreatment; Pegylated asparaginase; Lineage-targeted risk and minimal residual disease

Outcome Measures

Primary Outcomes (1)

• Number of patients on disease free survival (DFS).

  DFS is defined as the time interval between the evaluation of CR and relapse of the disease or death in first Complete Response (CR); patients still alive, in first CR, will be censored at the time of the last follow-up. In this case, the DFS will be truncated at 2 years.

  At two years.

Secondary Outcomes (11)

• The rate of patients in complete remission (CR).

  After approximately two months from start of treatment.

• The rate of early bone marrow MRD negativity.

  At 4 timepoints (week 4, 10, 16 22).

• Early bone marrow MRD response (<10-4).

  At 4 weeks following induction cycle 1 with Peg-ASP.

• Overall Survival (OS) estimation.

  At two years from diagnosis.

• Cumulative Incidence of Relapse (CIR) estimation.

  At two years from CR achievement.

Study Arms (1)

Study population

EXPERIMENTAL

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.

Drug: Prephase PDN + CY; Drug: Cycle 1 Induction; Drug: Cycle 2 Induction / Early consolidation; Drug: Cycle 3 Early consolidation; Drug: Cycle 4 Consolidation; Drug: Cycle 5 Consolidation; Drug: Cycle 6 Consolidation; Drug: Cycle 7 Consolidation; Drug: Cycle 8 Reinduction; Drug: Maintenance; Procedure: Allogeneic SCT or Autologous SCT

Interventions

Prephase PDN + CY DRUG

Study population

Cycle 1 Induction DRUG

Also known as: VCR + IDR + DXM + ASP + IT

Study population

Cycle 2 Induction / Early consolidation DRUG

Also known as: IDR + CY + ARA-C + ASP + 6MP + DXM + IT

Study population

Cycle 3 Early consolidation DRUG

Also known as: MTX + ARA-C

Study population

Cycle 4 Consolidation DRUG

Also known as: VCR + IDR + CY + ARA-C + 6-MP + DXM + IT

Study population

Cycle 5 Consolidation DRUG

Also known as: MTX + ASP + 6-MP

Study population

Cycle 6 Consolidation DRUG

Also known as: VCR + IDR + CY + ARA-C + ASP + 6MP + DXM + IT

Study population

Cycle 7 Consolidation DRUG

Also known as: MTX + ARA-C

Study population

Cycle 8 Reinduction DRUG

Also known as: VCR + IDR + DXM + PDN + CY + IT

Study population

Maintenance DRUG

If MRD negative MRD u/k SR

Also known as: CY or VP and 6MP/MTX + 12 cycles of 6MP/MTX

Study population

Allogeneic SCT or Autologous SCT PROCEDURE

If MRD positive MRD u/k HR

Also known as: + Maintenance

Study population

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- 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gruppo Italiano Malattie EMatologiche dell'Adulto: lead

Study Sites (61)

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

Alessandria, Italy

Location

Azienda Ospedaliero - Universitaria 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

Azienda Ospedaliera - Papa Giovanni XXIII

Bergamo, Italy

Location

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

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

Cagliari, Italy

Location

CTMO - Ematologia - Ospedale "Binaghi"

Cagliari, Italy

Location

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

Caserta, Italy

Location

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

Catania, Italy

Location

Unità Operativa Complessa di Ematologia - Arcispedale S. Maria Nuova

Cona, Italy

Location

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

Cremona, Italy

Location

S.C. Ematologia ASO S. Croce e Carle

Cuneo, Italy

Location

IRCCS_AOU San Martino-IST.Clinica Ematologica

Genova, Italy

Location

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

Lecce, Italy

Location

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

Messina, Italy

Location

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

Mestre, Italy

Location

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

Milan, Italy

Location

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

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 "S.Gerardo"

Monza, Italy

Location

Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli"

Napoli, Italy

Location

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

Novara, Italy

Location

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

Nuoro, Italy

Location

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

Orbassano, Italy

Location

Università degli Studi di Padova - Ematologia ed Immunologia Clinica

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

Palermo, Italy

Location

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

Palmero, Italy

Location

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

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

Div. di Ematologia di Muraglia - CTMO Ospedale San Salvatore

Pesaro, Italy

Location

U.O. Ematologia Clinica - Azienda USL di Pescara

Pescara, Italy

Location

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

Piacenza, Italy

Location

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

Pisa, Italy

Location

Ematologia - Ospedale San Carlo

Potenza, Italy

Location

Dipartimento Oncologico - Ospedale S.Maria delle Croci

Ravenna, Italy

Location

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

Reggio Calabria, Italy

Location

Unità Operativa Complessa di Ematologia - Arcispedale S. Maria Nuova

Reggio Emilia, Italy

Location

Ospedale "Infermi"

Rimini, Italy

Location

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

Roma, Italy

Location

Complesso Ospedaliero S. Giovanni Addolorata

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

Roma, Italy

Location

Sezione di Ematologia Cancer Center Humanitas

Rozzano, Italy

Location

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

Siena, Italy

Location

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

Torino, Italy

Location

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

Torino, Italy

Location

Ospedale Mauriziano Umberto I - Torino - Scdu Ematologia

Torino, Italy

Location

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

Treviso, Italy

Location

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

Udine, Italy

Location

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

Verona, Italy

Location

Related Publications (2)

• 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.

  PMID: 37276451 DERIVED

• 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.

  PMID: 34048072 DERIVED

Related Links

• GIMEMA Foundation

MeSH Terms

Conditions

Neoplasm Metastasis; Neoplasm, Residual

Interventions

aspartyl-aspartic acid; Cytarabine; Mercaptopurine; Maintenance

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Sulfhydryl Compounds; Sulfur Compounds; Organic Chemicals; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Health Care Facilities Workforce and Services

Study Officials

• Renato Bassan, Pr.

  Azienda ULSS 12 Veneziana

  STUDY CHAIR

• Roberto Foà, Pr.

  Policlinico Umberto I, Hematology Department.

  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: February 17, 2014
• First Posted: February 20, 2014
• Study Start: May 20, 2014
• Primary Completion: October 7, 2016
• Study Completion: December 7, 2020
• Last Updated: September 8, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

IT (61)