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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02067143
Other study ID # LAL1913
Secondary ID
Status Completed
Phase Phase 2
First received
Last updated
Start date May 20, 2014
Est. completion date December 7, 2020

Study information

Verified date September 2021
Source Gruppo Italiano Malattie EMatologiche dell'Adulto
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

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.


Recruitment information / eligibility

Status Completed
Enrollment 204
Est. completion date December 7, 2020
Est. primary completion date October 7, 2016
Accepts healthy volunteers No
Gender All
Age group 18 Years to 65 Years
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Prephase PDN + CY

Cycle 1 Induction

Cycle 2 Induction / Early consolidation

Cycle 3 Early consolidation

Cycle 4 Consolidation

Cycle 5 Consolidation

Cycle 6 Consolidation

Cycle 7 Consolidation

Cycle 8 Reinduction

Maintenance
If MRD negative MRD u/k SR
Procedure:
Allogeneic SCT or Autologous SCT
If MRD positive MRD u/k HR

Locations

Country Name City State
Italy S.O.C. di Ematologia - Azienda Ospedaliera - SS. Antonio e Biagio e Cesare Arrigo Alessandria
Italy Azienda Ospedaliero - Universitaria Ospedali Riuniti Umberto I - G.M. LANCISI - G. SALESI Ancona
Italy U.O.C. Ematologia e Terapia Cellulare - Ospedale "C. e G. Mazzoni" di Ascoli Piceno Ascoli Piceno
Italy Az.Ospedaliera S.G.Moscati Avellino
Italy UO Ematologia con trapianto-Università degli Studi di Bari Aldo Moro Bari
Italy Azienda Ospedaliera - Papa Giovanni XXIII Bergamo
Italy Istituto di Ematologia "Lorenzo e A. Seragnoli" - Università degli Studi di Bologna - Policlinico S. Orsola - Malpighi Bologna
Italy Comprensorio Sanitario di Bolzano - Azienda Sanitaria dell'Alto Adige - Ematologia e Centro TMO - Ospedale S.Maurizio Bolzano
Italy Spedali Civili - Brescia - Azienda Ospedaliera - U.O. Ematologia Brescia
Italy Divisione di Ematologia Ospedale A. Perrino Brindisi
Italy Ao Brotzu, Presidio Ospedaliero A. Businco - Cagliari - Sc Ematologia E Ctmo Cagliari
Italy CTMO - Ematologia - Ospedale "Binaghi" Cagliari
Italy Unità Operativa Complessa di Onco-Ematologia - A.O. S.Anna e S.Sebastiano Caserta
Italy Università di Catania - Cattedra di Ematologia - Ospedale "Ferrarotto" Catania
Italy Unità Operativa Complessa di Ematologia - Arcispedale S. Maria Nuova Cona
Italy Sezione di Ematologia C.T.M.O. Istituti Ospitalieri Cremona
Italy S.C. Ematologia ASO S. Croce e Carle Cuneo
Italy IRCCS_AOU San Martino-IST.Clinica Ematologica Genova
Italy ASL Le/1 P.O. Vito Fazzi - U.O. di Ematologia ed UTIE Lecce
Italy Divisione di Ematologia - Azienda Ospedaliera Ospedali Riuniti "Papardo Piemonte" P.O. Papardo Messina
Italy U.O. di Ematologia- Ospedale dell'Angelo - Mestre Mestre
Italy Fondazione Irccs Ca' Granda, Ospedale Maggiore Policlinico - Milano - Ematologia - Padiglione Marcora Milano
Italy Ospedale Niguarda " Ca Granda" - SC Ematologia Blocco SUD, Ponti Est, Scala E, 4° piano Milano
Italy U.O. Ematologia e Trapianto di MIdollo - Ist.Scientifico Ospedale San Raffaele Milano
Italy UO Ematologia - AOU Policlinico di Modena Modena
Italy Azienda Ospedaliera "S.Gerardo" Monza
Italy Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli" Napoli
Italy S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro Novara
Italy U.O. CTMO Ematologia - Osp. S.Francesco Nuoro
Italy Dip. di Scienze Cliniche e Biologiche - Ospedale S. Luigi Gonzaga-Medicina Interna 2 Orbassano
Italy Università degli Studi di Padova - Ematologia ed Immunologia Clinica Padova
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 Dipart. Biomedico di Medicina Interna - A.U. Policlinico "Paolo Giaccone" Palermo
Italy Casa Di Cura La Maddalena S.P.A. - Dipartimento Oncologico Di Iii Livello - Palermo - Uo Oncoematologia E Tmo Palmero
Italy Day Hospital dell'U.O.C di Ematologia e CTMO Padiglione 1 TORRE DELLE MEDICINE, 6° piano Parma
Italy S.C. Ematologia - Fondazione IRCCS Policlinico S. Matteo Pavia
Italy Sezione di Ematologia ed Immunologia Clinica - Ospedale S.Maria della Misericordia Perugia
Italy Div. di Ematologia di Muraglia - CTMO Ospedale San Salvatore Pesaro
Italy U.O. Ematologia Clinica - Azienda USL di Pescara Pescara
Italy Unità Operativa Ematologia e Centro Trapianti - Dipartimento di Oncologia ed Ematologia - AUSL Ospedale G. da Saliceto Piacenza
Italy Università di Pisa - Azienda Ospedaliera Pisana - Dipartimento di Oncologia, dei Trapianti e delle nuove Tecnologie in Medicina - Divisione di Ematologia Pisa
Italy Ematologia - Ospedale San Carlo Potenza
Italy Dipartimento Oncologico - Ospedale S.Maria delle Croci Ravenna
Italy Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli" Reggio Calabria
Italy Unità Operativa Complessa di Ematologia - Arcispedale S. Maria Nuova Reggio Emilia
Italy Ospedale "Infermi" Rimini
Italy Az. Ospedaliera "Sant' Andrea"-Università la Sapienza Seconda Facoltà di Medicina e Chirurgia Roma
Italy Complesso Ospedaliero S. Giovanni Addolorata Roma
Italy S.C. di Ematologia e Trapianti - I.F.O. Istituto Nazionale Tumori Regina Elena Roma
Italy U.O.C. Ematologia - Ospedale S.Eugenio Roma
Italy Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia Roma
Italy Sezione di Ematologia Cancer Center Humanitas Rozzano
Italy UOC di Ematologia e Trapianti di Cellule Staminali Emopoietiche - AOU San Giovanni di Dio e Ruggi D'Aragona Salerno
Italy Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza San Giovanni Rotondo
Italy U.O.C. Ematologia e Trapianti - A.O. Senese - Policlinico " Le Scotte" Siena
Italy Dipartimento di Oncologia ed Ematologia S.C. Ematologia 2 A.O. Città della Salute e della Scienza di Torino San Giovanni Battista Torino
Italy Divisione di Ematologia dell' Università degli Studi di Torino - "Città della Salute e della Scienza di Torino" Torino
Italy Ospedale Mauriziano Umberto I - Torino - Scdu Ematologia Torino
Italy U.L.S.S. 9 UOC Ematologia - Ospedale Ca' Foncello Treviso
Italy Clinica Ematologica-Centro Trapianti e Terapie cellulari Azienda Ospedaliero-Universitaria, Udine Udine
Italy Università degli Studi di Verona - A. O. - Istituti Ospitalieri di Verona- Div. di Ematologia - Policlinico G.B. Rossi Verona

Sponsors (1)

Lead Sponsor Collaborator
Gruppo Italiano Malattie EMatologiche dell'Adulto

Country where clinical trial is conducted

Italy, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 The rate of patients in complete remission (CR). After approximately two months from start of treatment.
Secondary The rate of early bone marrow MRD negativity. At 4 timepoints (week 4, 10, 16 22).
Secondary Early bone marrow MRD response (<10-4). At 4 weeks following induction cycle 1 with Peg-ASP.
Secondary Overall Survival (OS) estimation. At two years from diagnosis.
Secondary Cumulative Incidence of Relapse (CIR) estimation. At two years from CR achievement.
Secondary The rate of patients dead due Treatment-related mortality (TRM). By the end of the study (4.5 years from first centre opened).
Secondary Composite DFS, OS, CIR. At two years from CR achievement and rate of TRM in LL patients.
Secondary Description of Minimal Residual Disease (MRD) monitoring. During treatment at time point 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12.
Secondary Number of Severe Infections (SI) during treatment. Description: Number and type. At the end of the study (4.5 years from first centre opened).
Secondary Rate of Adverse Events (AE). Excluding SI. By the end of the study (4.5 years from first centre opened)
Secondary Composite evaluation of impact of age (=55 and >55) and risk category group (SR, HR, VHR - as defined) on outcomes: DFS, CIR. At two years for CR achievement, OS at two years from diagnosis and TRM.
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