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
Related Research Topics
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Trial Locations
- Locations (74)
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
Scroll for more (64 remaining)Ospedale Umberto I - DH Oncoematologico🇮🇹Nocera Inferiore, Salerno, Italy