Dose Dense Chemotherapy + Rituximab +/-Intensified High Dose Chemoimmunotherapy With Support of Peripheral Autologous Stem Cell in Diffuse Large B-Cell Lymphoma
- Conditions
- Diffuse Large B-Cell LymphomaIPI≥2
- Interventions
- Registration Number
- NCT00499018
- Lead Sponsor
- Fondazione Italiana Linfomi - ETS
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 399
- 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.
-
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
-
LFEV<45%
-
Severe diabetes mellitus difficult to control with adequate insulin therapy
-
Severe chronic obstructive pulmonary disease with hypoxemia
-
Active bacterial, viral of fungal infection requiring systemic therapy
-
Concurrent thrombohemolytic disease
-
HIV positivity
-
HBV positivity
-
Positive serology for HBV (occult carriers: AntiHBc+, HbsAg-, AntiHbs+/-) with positive HBV-DNA test
-
HCV positivity in presence of replication marks (HCV+, CRP+, AST 1,5-2 times normal ranges)
-
CNS localization of disease
-
Prior (during last 3 years) or concurrent malignancy except adequately treated basal cell carcinoma of the skin or carcinoma in situ of the cervix or early stage prostate cancer not requiring systemic therapy, or early breast cancer treated with surgery alone. Any other co.existing medical condition that would preclude study therapy administration
-
Pregnancy or breast-feeding women
-
Inability of the patient to give her/his informed consent
-
Known hypersensitivity or anaphylactic reaction to murine antibodies or proteins
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 2 Pegfilgrastim R-MegaCHOP14 x 4 Restaging + R-MegaCHOP x 2 1 ARA-C R-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT 1 Lenograstim R-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT 1 ASCT R-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT 1 BIS Vincristina R-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT 1 BIS ASCT R-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT 2 BIS Prednisone R-CHOP14 x 4 Restaging + R-CHOP14 x 4 1 Vincristina R-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT 1 Rituximab R-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT 1 Mitoxantrone R-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT 1 Ciclofosfamide R-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT 1 Doxorubicina R-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT 1 Pegfilgrastim R-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT 1 Prednisone R-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT 1 BCNU R-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT 1 VP-16 R-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT 1 BIS Rituximab R-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT 1 BIS Prednisone R-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT 1 BIS Pegfilgrastim R-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT 1 BIS ARA-C R-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT 1 BIS BCNU R-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT 1 BIS VP-16 R-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT 2 Rituximab R-MegaCHOP14 x 4 Restaging + R-MegaCHOP x 2 1 BIS Ciclofosfamide R-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT 1 BIS Doxorubicina R-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT 2 Ciclofosfamide R-MegaCHOP14 x 4 Restaging + R-MegaCHOP x 2 2 Doxorubicina R-MegaCHOP14 x 4 Restaging + R-MegaCHOP x 2 2 Vincristina R-MegaCHOP14 x 4 Restaging + R-MegaCHOP x 2 2 Prednisone R-MegaCHOP14 x 4 Restaging + R-MegaCHOP x 2 2 Mitoxantrone R-MegaCHOP14 x 4 Restaging + R-MegaCHOP x 2 2 ARA-C R-MegaCHOP14 x 4 Restaging + R-MegaCHOP x 2 2 BIS Rituximab R-CHOP14 x 4 Restaging + R-CHOP14 x 4 2 BIS Vincristina R-CHOP14 x 4 Restaging + R-CHOP14 x 4 2 BIS Ciclofosfamide R-CHOP14 x 4 Restaging + R-CHOP14 x 4 2 BIS Doxorubicina R-CHOP14 x 4 Restaging + R-CHOP14 x 4 1 BIS Lenograstim R-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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 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 the four different induction arms in terms of 2-years FFS (exploratory analysis). 2 years To evaluate the efficacy of two different dose-dense + Rituximab chemotherapy regimens in term of 2-years Failure Free Survival (FFS). 2 years
Trial Locations
- Locations (74)
Istituto Vito Fazzi
🇮🇹Lecce, Italy
Ospedale Umberto I - DH Oncoematologico
🇮🇹Nocera Inferiore, Salerno, Italy
Az. Osp. SS. Antonio e Biagio e Cesare Arrigo
🇮🇹Alessandria, Italy
Ospedale Policlinico S. Orsola Malpighi
🇮🇹Bologna, Italy
Stabilimento "Perrino"
🇮🇹Brindisi, Italy
Ospedale Civile Umberto I
🇮🇹Mestre, Venezia, Italy
Osp. Calvi, Noale
🇮🇹Mirano, Venezia, Italy
Azienda Ospedale Policlinico Consorziale
🇮🇹Bari, Italy
Osp. Degli Infermi
🇮🇹Biella, Italy
Centro di Riferimento Oncologico
🇮🇹Aviano - PN, Italy
IRCC Istituto tumori Ematologia
🇮🇹Bari, Italy
Spedali Civili
🇮🇹Brescia, Italy
Ospedale Cardinal Massaia
🇮🇹Asti, Italy
UTMO Ematologia Università Spedali Civili
🇮🇹Brescia, Italy
Ospedale di Circolo
🇮🇹Busto Arsizio - VA, Italy
IRCC
🇮🇹Candiolo (TO), Italy
Ospedale Pugliese
🇮🇹Catanzaro, Italy
Stabilimento Ospedaliero
🇮🇹Verbania, Italy
Ospedale Bufalini
🇮🇹Cesena - FC, Italy
Ospedale Generale di Zona
🇮🇹Civitanova Marche (MC), Italy
Presidio Ospedaliero Annunziata
🇮🇹Cosenza, Italy
Stabilimento Forlì
🇮🇹Forlì, Italy
Istituti Ospitalieri
🇮🇹Cremona, Italy
Azienda Universitaria San Martino
🇮🇹Genova, Italy
A.S.L. 9
🇮🇹Ivrea, Italy
Ospedale Felettino
🇮🇹La Spezia, Italy
Azienda Ospedaliera Papardo
🇮🇹Messina, Italy
Azienda Ospedaliero Universitaria Policlinico Gaetano Martino
🇮🇹Messina, Italy
Istituto Europeo di Oncologia
🇮🇹Milano, Italy
Osp. San Carlo Borromeo
🇮🇹Milano, Italy
Ospedale Cà Grande - Niguarda
🇮🇹Milano, Italy
Ospedale Fatebenefratelli
🇮🇹Milano, Italy
Presidio Osp. Maggiore Policlinico
🇮🇹Milano, Italy
Azienda Ospedaliera Policlinico
🇮🇹Modena, Italy
Università degli Studi Federico II
🇮🇹Napoli, Italy
Ospedale S. Gerardo
🇮🇹Monza, Italy
Ospedale S. Francesco
🇮🇹Nuoro, Italy
Ospedale San Luigi
🇮🇹Orbassano (TO), Italy
Azienda Ospedaliera
🇮🇹Padova, Italy
Fond. Maugeri - Centro medico
🇮🇹Pavia, Italy
Università degli Studi
🇮🇹Parma, 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 Nuova
🇮🇹Reggio Emilia, Italy
Ospedale Santa Maria delle Croci
🇮🇹Ravenna, Italy
Ospedale Bianchi Melacrino Morelli
🇮🇹Reggio Calabria, Italy
Ospedale S. Eugenio
🇮🇹Roma, Italy
Ospedale Oncologico Regionale
🇮🇹Rionero in Vulture (PZ), Italy
Università degli Studi di Roma "La Sapienza"
🇮🇹Roma, Italy
Istituto Regina Elena
🇮🇹Roma, Italy
Policlinico Universitario Campus Biomedico
🇮🇹Roma, Italy
Policlinico Universitario A. Gemelli
🇮🇹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
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
Policlinico Universitario
🇮🇹Udine, Italy
Ospedale Generale Prov. Cardinale G. Panico
🇮🇹Tricase (LE), Italy
Osp. di Circolo e Fondazione Macchi
🇮🇹Varese, Italy
Osp. Sant'Andrea Divisioen di Onco-Ematologia
🇮🇹Vercelli, Italy
Ospedale Armando Businco
🇮🇹Cagliari, Italy
Università Cattolica del Sacro Cuore
🇮🇹Campobasso, Italy
Az. Ospedaliero Universitaria Careggi
🇮🇹Firenze, Italy
Osp. Maggiore Della Carità
🇮🇹Novara, Italy
Ospedale SS.Annunziata
🇮🇹Sassari, Italy