MRD/Risk-oriented Therapy of Adult Ph- ALL Including Pegylated Asparaginase and Lineage-targeted Methotrexate (LAL1913)

September 6, 2021 updated by: Gruppo Italiano Malattie EMatologiche dell'Adulto

National Treatment Program of Philadelphia Chromosome-negative Adult Acute Lymphoblastic Leukemia With Pegylated Asparaginase Added to a Lineage-Targeted Risk- and Minimal Residual Disease-Oriented Strategy

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

204

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

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

Genders Eligible for Study

All

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- 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 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: 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.
Drug: Prephase PDN + CY
Drug: Cycle 1 Induction
Other Names:
  • VCR + IDR + DXM + ASP + IT
Drug: Cycle 2 Induction / Early consolidation
Other Names:
  • IDR + CY + ARA-C + ASP + 6MP + DXM + IT
Drug: Cycle 3 Early consolidation
Other Names:
  • MTX + ARA-C
Drug: Cycle 4 Consolidation
Other Names:
  • VCR + IDR + CY + ARA-C + 6-MP + DXM + IT
Drug: Cycle 5 Consolidation
Other Names:
  • MTX + ASP + 6-MP
Drug: Cycle 6 Consolidation
Other Names:
  • VCR + IDR + CY + ARA-C + ASP + 6MP + DXM + IT
Drug: Cycle 7 Consolidation
Other Names:
  • MTX + ARA-C
Drug: Cycle 8 Reinduction
Other Names:
  • VCR + IDR + DXM + PDN + CY + IT
Drug: Maintenance
If MRD negative MRD u/k SR
Other Names:
  • CY or VP and 6MP/MTX + 12 cycles of 6MP/MTX
Procedure: Allogeneic SCT or Autologous SCT
If MRD positive MRD u/k HR
Other Names:
  • + Maintenance

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients on disease free survival (DFS).
Time Frame: At two years.
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 Outcome Measures

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

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, Pr., Azienda ULSS 12 Veneziana
  • Study Director: Roberto Foà, Pr., Policlinico Umberto I, Hematology Department.

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.

General Publications

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)

May 20, 2014

Primary Completion (Actual)

October 7, 2016

Study Completion (Actual)

December 7, 2020

Study Registration Dates

First Submitted

February 17, 2014

First Submitted That Met QC Criteria

February 18, 2014

First Posted (Estimate)

February 20, 2014

Study Record Updates

Last Update Posted (Actual)

September 8, 2021

Last Update Submitted That Met QC Criteria

September 6, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LAL1913

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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.

Clinical Trials on Secondary

Clinical Trials on Prephase PDN + CY

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Israel

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe