Dose Dense Chemotherapy + Rituximab +/-Intensified High Dose Chemoimmunotherapy With Support of Peripheral Autologous Stem Cell in Diffuse Large B-Cell Lymphoma
DLCL04
A Randomised Multicentric Phase III Study for the Treatment of Young Patients With High Risk (IPI 2-3) Diffuse Large B-Cell Lymphoma. Dose Dense Chemotherapy + Rituximab +/- Intensified High Dose Chemoimmunotherapy With Support of Peripheral Autologous Stem Cells.
2 other identifiers
interventional
399
1 country
75
Brief Summary
The purpose of this study is to define an improvement in patients randomized in four different arms: Arm 1: R-MegaCHOP14x4 + R-MAD + MAD + BEAM + ASCT; Arm 1BIS: R-CHOP14x4 + R-MAD + MAD + BEAM + ASCT; Arm 2: R-MegaCHOP14x4 + R-MegaCHOP14x2; Arm 2BIS: R-CHOP14x4 + R-CHOP14x4; Which are different in dose dense chemotherapy + Rituximab with or without intensified high dose chemoimmunotherapy and support of peripheral autologous stem cells.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jan 2006
Longer than P75 for phase_3
75 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 1, 2006
CompletedFirst Submitted
Initial submission to the registry
July 10, 2007
CompletedFirst Posted
Study publicly available on registry
July 11, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2013
CompletedFebruary 15, 2011
February 1, 2011
5.4 years
July 10, 2007
February 14, 2011
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
To evaluate the activity of arms "R-MegaCHOP14/R-CHOP14 + R-MAD+BEAM and ASCT" and "R-MegaCHOP14/R-CHOP14" in terms of 2-years Failure Free Survival (FFS).
2 years
Secondary Outcomes (4)
To evaluate the activity of arms "R-MegaCHOP14/R-CHOP14 + R-MAD+BEAM and ASCT" and "R-MegaCHOP14/R-CHOP14" in terms of 3-years Overall Survival (OS).
3 years
To evaluate the efficacy of two different dose-dense + Rituximab chemotherapy regimens in term of 2-years Failure Free Survival (FFS).
2 years
To evaluate the activity of the first four courses of two different dose dense + Rituximab chemotherapy regimens (standard dose R-CHOP14 or intensified dose R-MegaCHOP14) in terms of Overall Response Rate (ORR) and Complete Remission (RC).
2 years
To evaluate the efficacy of the four different induction arms in terms of 2-years FFS (exploratory analysis).
2 years
Study Arms (4)
1
EXPERIMENTALR-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
1 BIS
EXPERIMENTALR-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
2
EXPERIMENTALR-MegaCHOP14 x 4 Restaging + R-MegaCHOP x 2
2 BIS
EXPERIMENTALR-CHOP14 x 4 Restaging + R-CHOP14 x 4
Interventions
Eligibility Criteria
You may qualify if:
- Age 18-60;
- Histological confirmed diagnosis of Diffuse Large B-Cell Lymphoma CD20+ (newly diagnosis or shifted from low grade NHL and not previously treated) or of Follicular Lymphoma grade III according to REAL/WHO Classification.
- Advanced stage II, stage III and stage IV with at least two aa-IPI risk factors.
- Age-adjusted IPI 2-3.
- ECOG performance status 0-2.
- LVEF\>45%, measured with echocardiography.
- Normal hepatic, renal and pulmonary functions.
- HIV, HCV and HBV negativity.
- HCV+ admitted only in histologically confirmed absence of replication marks.
- Positive serology for HBV (occult carriers: AntiHBcAg+, HbsAg-, AntiHBsAg+/-) admitted only upon negativity of weakly positive HBV-DNA test.
- Life expectancy \> 3 months.
- Negative pregnancy test.
- Written Informed Consent.
You may not qualify if:
- Histological diagnosis of:
- Lymphoblastic NHL
- Burkitt's Lymphoma
- CD 20 negative B-cell Lymphoma
- grade I-IIIa Follicular Lymphoma
- Mantle Cell Lymphoma
- Primary mediastinal NHL with exclusively intrathoracic localization.
- Age \> 60
- Stage I disease
- Age-adjusted IPI 0-1
- ECOG-PS\>3, if not related to Lymphoma
- Renal impairment (creatinine\>1,2 mg/dl or creatinine clearance \< 60ml/min)
- Hepatic impairment (AST/ALT or bilirubin \> 2,5 times normal limit, unless due to Lymphoma)
- HIV positive patients and/or with HBV or HCV active infection(documented by HBV-DNA and HCV-RNA positive tests)
- Clinically significant secondary cardiovascular disease e.g. uncontrolled hypertension (resting diastolic blood pressure \> 115 mmHG), uncontrolled multifocal cardiac arrhythmias, symptomatic angina pectoris or congestive cardiac failure NYHA class III-IV
- +14 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (75)
Ospedale Umberto I - DH Oncoematologico
Nocera Inferiore, Salerno, Italy
Ospedale Civile Umberto I
Mestre, Venezia, Italy
Osp. Calvi, Noale
Mirano, Venezia, Italy
Az. Osp. SS. Antonio e Biagio e Cesare Arrigo
Alessandria, Italy
Ospedale Cardinal Massaia
Asti, Italy
Centro di Riferimento Oncologico
Aviano - PN, Italy
Azienda Ospedale Policlinico Consorziale
Bari, Italy
IRCC Istituto tumori Ematologia
Bari, Italy
Osp. Degli Infermi
Biella, Italy
Ospedale Policlinico S. Orsola Malpighi
Bologna, Italy
Spedali Civili
Brescia, Italy
UTMO Ematologia Università Spedali Civili
Brescia, Italy
Stabilimento "Perrino"
Brindisi, Italy
Ospedale di Circolo
Busto Arsizio - VA, Italy
Ospedale Armando Businco
Cagliari, Italy
Università Cattolica del Sacro Cuore
Campobasso, Italy
IRCC
Candiolo (TO), Italy
Ospedale Pugliese
Catanzaro, Italy
Ospedale Bufalini
Cesena - FC, Italy
Stabilimento Ospedaliero
Ciriè - to, Italy
Ospedale Generale di Zona
Civitanova Marche (MC), Italy
Presidio Ospedaliero Annunziata
Cosenza, Italy
Istituti Ospitalieri
Cremona, Italy
Az. Ospedaliero Universitaria Careggi
Florence, Italy
Stabilimento Forlì
Forlì, Italy
Azienda Universitaria San Martino
Genova, Italy
A.S.L. 9
Ivrea, Italy
Ospedale Felettino
La Spezia, Italy
Istituto Vito Fazzi
Lecce, Italy
Azienda Ospedaliera Papardo
Messina, Italy
Azienda Ospedaliero Universitaria Policlinico Gaetano Martino
Messina, Italy
Istituto Europeo di Oncologia
Milan, Italy
Osp. San Carlo Borromeo
Milan, Italy
Ospedale Cà Grande - Niguarda
Milan, Italy
Ospedale Fatebenefratelli
Milan, Italy
Presidio Osp. Maggiore Policlinico
Milan, Italy
Azienda Ospedaliera Policlinico
Modena, Italy
Ospedale S. Gerardo
Monza, Italy
Università degli Studi Federico II
Napoli, Italy
Osp. Maggiore Della Carità
Novara, Italy
Ospedale S. Francesco
Nuoro, Italy
Ospedale San Luigi
Orbassano (TO), Italy
Azienda Ospedaliera
Padua, Italy
Università degli Studi
Parma, Italy
Fond. Maugeri - Centro medico
Pavia, Italy
Ospedale Policlinico San Matteo
Pavia, Italy
Ospedale di Piacenza
Piacenza, Italy
Azienda Ospedaliero Universitaria Pisana
Pisa, Italy
Azienda Ospedaliera Ospedale San Carlo
Potenza, Italy
Ospedale Santa Maria delle Croci
Ravenna, Italy
Ospedale Bianchi Melacrino Morelli
Reggio Calabria, Italy
Ospedale Santa Maria Nuova
Reggio Emilia, Italy
Ospedale Oncologico Regionale
Rionero in Vulture (PZ), Italy
Istituto Regina Elena
Roma, Italy
Ospedale S. Eugenio
Roma, Italy
Policlinico Universitario A. Gemelli
Roma, Italy
Policlinico Universitario Campus Biomedico
Roma, Italy
Università degli Studi di Roma "La Sapienza"
Roma, Italy
Università degli Studi di Roma 'Tor Vergata'
Roma, Italy
Ospedale di Ronciglione
Ronciglione (VT), Italy
Istituto Clinico Humanitas
Rozzano - MI, Italy
Casa Sollievo della Sofferenza
San Giovanni Rotondo (FG), Italy
Ospedale SS.Annunziata
Sassari, Italy
Spedali Riuniti
Siena, Italy
Ospedale Morelli
Sondalo, Italy
Stabilimento SS. Annunziata
Taranto, Italy
Azienda Ospedaliera di Perugia
Terni, Italy
Osp. S. Giovanni Battista "Molinette"
Torino, Italy
Ospedale Ca Focello
Treviso, Italy
Presidio Ospedaliero di Vittorio Veneto
Treviso, Italy
Ospedale Generale Prov. Cardinale G. Panico
Tricase (LE), Italy
Policlinico Universitario
Udine, Italy
Osp. di Circolo e Fondazione Macchi
Varese, Italy
Stabilimento Ospedaliero
Verbania, Italy
Osp. Sant'Andrea Divisioen di Onco-Ematologia
Vercelli, Italy
Related Publications (2)
Derenzini E, Mazzara S, Melle F, Motta G, Fabbri M, Bruna R, Agostinelli C, Cesano A, Corsini CA, Chen N, Righi S, Sabattini E, Chiappella A, Calleri A, Fiori S, Tabanelli V, Cabras A, Pruneri G, Vitolo U, Gianni AM, Rambaldi A, Corradini P, Zinzani PL, Tarella C, Pileri S. A three-gene signature based on MYC, BCL-2 and NFKBIA improves risk stratification in diffuse large B-cell lymphoma. Haematologica. 2021 Sep 1;106(9):2405-2416. doi: 10.3324/haematol.2019.236455.
PMID: 32817282DERIVEDChiappella A, Martelli M, Angelucci E, Brusamolino E, Evangelista A, Carella AM, Stelitano C, Rossi G, Balzarotti M, Merli F, Gaidano G, Pavone V, Rigacci L, Zaja F, D'Arco A, Cascavilla N, Russo E, Castellino A, Gotti M, Congiu AG, Cabras MG, Tucci A, Agostinelli C, Ciccone G, Pileri SA, Vitolo U. Rituximab-dose-dense chemotherapy with or without high-dose chemotherapy plus autologous stem-cell transplantation in high-risk diffuse large B-cell lymphoma (DLCL04): final results of a multicentre, open-label, randomised, controlled, phase 3 study. Lancet Oncol. 2017 Aug;18(8):1076-1088. doi: 10.1016/S1470-2045(17)30444-8. Epub 2017 Jun 28.
PMID: 28668386DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Umberto Vitolo, MD
S.C. Ematologia II - OSP.S. GIOV.BATTISTA MOLINETTE - TORINO (TO) -
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
Study Record Dates
First Submitted
July 10, 2007
First Posted
July 11, 2007
Study Start
January 1, 2006
Primary Completion
June 1, 2011
Study Completion
September 1, 2013
Last Updated
February 15, 2011
Record last verified: 2011-02