AzTrials
AzTrials

Untreated Philadelphia Positive Acute Lymphoblastic LeukemiaPhase 2LAL1913NCT02067143

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

A Phase 2 study testing Prephase PDN + CY, Cycle 1 Induction and Cycle 2 Induction / Early consolidation in people with Untreated Philadelphia Positive Acute Lymphoblastic Leukemia and De Novo, run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 61 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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… Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
Prephase PDN + CY, Cycle 1 Induction and Cycle 2 Induction / Early consolidation
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
204 participants
Where
61 sitesItaly
Study dates
20 May 2014to 7 Dec 2020
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

61 sites in 1 country.

61 sites in 1 country

Italy61 sites

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

    Alessandria

  • Azienda Ospedaliero - Universitaria Ospedali Riuniti Umberto I - G.M. LANCISI - G. SALESI

    Ancona

  • U.O.C. Ematologia e Terapia Cellulare - Ospedale "C. e G. Mazzoni" di Ascoli Piceno

    Ascoli Piceno

  • Az.Ospedaliera S.G.Moscati

    Avellino

  • UO Ematologia con trapianto-Università degli Studi di Bari Aldo Moro

    Bari

  • Azienda Ospedaliera - Papa Giovanni XXIII

    Bergamo

  • Istituto di Ematologia "Lorenzo e A. Seragnoli" - Università degli Studi di Bologna - Policlinico S. Orsola - Malpighi

    Bologna

  • Comprensorio Sanitario di Bolzano - Azienda Sanitaria dell'Alto Adige - Ematologia e Centro TMO - Ospedale S.Maurizio

    Bolzano

  • Spedali Civili - Brescia - Azienda Ospedaliera - U.O. Ematologia

    Brescia

  • Divisione di Ematologia Ospedale A. Perrino

    Brindisi

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

    Cagliari

  • CTMO - Ematologia - Ospedale "Binaghi"

    Cagliari

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

    Caserta

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

    Catania

  • Unità Operativa Complessa di Ematologia - Arcispedale S. Maria Nuova

    Cona

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

    Cremona

  • S.C. Ematologia ASO S. Croce e Carle

    Cuneo

  • IRCCS_AOU San Martino-IST.Clinica Ematologica

    Genova

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

    Lecce

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

    Messina

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

    Mestre

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

    Milan

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

    Milan

  • U.O. Ematologia e Trapianto di MIdollo - Ist.Scientifico Ospedale San Raffaele

    Milan

  • UO Ematologia - AOU Policlinico di Modena

    Modena

  • Azienda Ospedaliera "S.Gerardo"

    Monza

  • Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli"

    Naples

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

    Novara

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

    Nuoro

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

    Orbassano

  • Università degli Studi di Padova - Ematologia ed Immunologia Clinica

    Padova

  • Ospedali Riuniti "Villa Sofia-Cervello"

    Palermo

  • 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

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

    Palmero

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

    Parma

  • S.C. Ematologia - Fondazione IRCCS Policlinico S. Matteo

    Pavia

  • Sezione di Ematologia ed Immunologia Clinica - Ospedale S.Maria della Misericordia

    Perugia

  • Div. di Ematologia di Muraglia - CTMO Ospedale San Salvatore

    Pesaro

  • U.O. Ematologia Clinica - Azienda USL di Pescara

    Pescara

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

    Piacenza

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

    Pisa

  • Ematologia - Ospedale San Carlo

    Potenza

  • Dipartimento Oncologico - Ospedale S.Maria delle Croci

    Ravenna

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

    Reggio Calabria

  • Unità Operativa Complessa di Ematologia - Arcispedale S. Maria Nuova

    Reggio Emilia

  • Ospedale "Infermi"

    Rimini

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

    Roma

  • Complesso Ospedaliero S. Giovanni Addolorata

    Roma

  • S.C. di Ematologia e Trapianti - I.F.O. Istituto Nazionale Tumori Regina Elena

    Roma

  • U.O.C. Ematologia - Ospedale S.Eugenio

    Roma

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

    Roma

  • Sezione di Ematologia Cancer Center Humanitas

    Rozzano

  • UOC di Ematologia e Trapianti di Cellule Staminali Emopoietiche - AOU San Giovanni di Dio e Ruggi D'Aragona

    Salerno

  • Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza

    San Giovanni Rotondo

  • U.O.C. Ematologia e Trapianti - A.O. Senese - Policlinico " Le Scotte"

    Siena

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

    Torino

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

    Torino

  • Ospedale Mauriziano Umberto I - Torino - Scdu Ematologia

    Torino

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

    Treviso

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

    Udine

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

    Verona

Other trials in Italy

About this study

Official title: 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.

Read the 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.

Being tested
Prephase PDN + CY, Cycle 1 Induction, Cycle 2 Induction / Early consolidation, Cycle 3 Early consolidation, Cycle 4 Consolidation
Keywords
Untreated philadelphia positive acute lymphoblastic leukemia, De novo, Secondary, Low-dose corticosteroids pretreatment, Pegylated asparaginase, Lineage-targeted risk and minimal residual disease
Medical subject headings
Neoplasm Metastasis, Neoplasm, Residual

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Prephase PDN + CYDrug

  • Cycle 1 InductionDrug

    Also called VCR + IDR + DXM + ASP + IT

  • Cycle 2 Induction / Early consolidationDrug

    Also called IDR + CY + ARA-C + ASP + 6MP + DXM + IT

  • Cycle 3 Early consolidationDrug

    Also called MTX + ARA-C

  • Cycle 4 ConsolidationDrug

    Also called VCR + IDR + CY + ARA-C + 6-MP + DXM + IT

  • Cycle 5 ConsolidationDrug

    Also called MTX + ASP + 6-MP

  • Cycle 6 ConsolidationDrug

    Also called VCR + IDR + CY + ARA-C + ASP + 6MP + DXM + IT

  • Cycle 7 ConsolidationDrug

    Also called MTX + ARA-C

  • Cycle 8 ReinductionDrug

    Also called VCR + IDR + DXM + PDN + CY + IT

  • MaintenanceDrug

    Also called CY or VP and 6MP/MTX + 12 cycles of 6MP/MTX

    If MRD negative MRD u/k SR

  • Allogeneic SCT or Autologous SCTProcedure or surgery

    Also called + Maintenance

    If MRD positive MRD u/k HR

Study groups in NCT02067143
Study groupRoleWhat they receive
Study populationExperimentalIn 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.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: At two years.

Secondary outcomes (11)

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

    Measured: After approximately two months from start of treatment.

  2. The rate of early bone marrow MRD negativity.

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

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

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

  4. Overall Survival (OS) estimation.

    Measured: At two years from diagnosis.

  5. Cumulative Incidence of Relapse (CIR) estimation.

    Measured: At two years from CR achievement.

  6. The rate of patients dead due Treatment-related mortality (TRM).

    Measured: By the end of the study (4.5 years from first centre opened).

  7. Composite DFS, OS, CIR.

    Measured: At two years from CR achievement and rate of TRM in LL patients.

  8. Description of Minimal Residual Disease (MRD) monitoring.

    Measured: During treatment at time point 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12.

  9. Number of Severe Infections (SI) during treatment.

    Description: Number and type.

    Measured: At the end of the study (4.5 years from first centre opened).

  10. Rate of Adverse Events (AE).

    Excluding SI.

    Measured: By the end of the study (4.5 years from first centre opened)

  11. Composite evaluation of impact of age (≤55 and >55) and risk category group (SR, HR, VHR - as defined) on outcomes: DFS, CIR.

    Measured: At two years for CR achievement, OS at two years from diagnosis and TRM.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Feb 2014 (estimated)
  2. Study start20 May 2014
  3. Primary completion7 Oct 2016
  4. Study completion7 Dec 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
204 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02067143
Sponsor's protocol ID
LAL1913
Acronym
LAL1913
Status last verified
Sep 2021
First submitted
17 Feb 2014
Last updated
8 Sep 2021
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • 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.

    PubMed 37276451

  • 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.

    PubMed 34048072

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Prephase PDN + CY, Cycle 1 Induction and Cycle 2 Induction / Early consolidation in people with Untreated Philadelphia Positive Acute Lymphoblastic Leukemia and De Novo, run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 61 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 61 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of patients on disease free survival (DFS). (time frame: At two years.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02067143, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Sep 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in