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.
Overview
- Phase
- Phase 3
- Intervention
- Prednisone
- Conditions
- Diffuse Large B-Cell Lymphoma
- Sponsor
- Fondazione Italiana Linfomi - ETS
- Enrollment
- 399
- Locations
- 74
- Primary Endpoint
- 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).
- Last Updated
- 15 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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-
- •ECOG performance status 0-
- •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.
Exclusion Criteria
- •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.
- •Stage I disease
- •Age-adjusted IPI 0-1
- •ECOG-PS\>3, if not related to Lymphoma
Arms & Interventions
2 BIS
R-CHOP14 x 4 Restaging + R-CHOP14 x 4
Intervention: Prednisone
1
R-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
Intervention: Rituximab
1
R-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
Intervention: Ciclofosfamide
2
R-MegaCHOP14 x 4 Restaging + R-MegaCHOP x 2
Intervention: Doxorubicina
1
R-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
Intervention: Doxorubicina
1
R-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
Intervention: Vincristina
1
R-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
Intervention: Prednisone
1
R-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
Intervention: Pegfilgrastim
1
R-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
Intervention: Mitoxantrone
1
R-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
Intervention: ARA-C
1
R-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
Intervention: Lenograstim
1
R-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
Intervention: BCNU
1
R-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
Intervention: VP-16
1
R-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
Intervention: ASCT
1 BIS
R-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
Intervention: Rituximab
1 BIS
R-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
Intervention: Vincristina
1 BIS
R-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
Intervention: Prednisone
1 BIS
R-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
Intervention: Pegfilgrastim
1 BIS
R-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
Intervention: Lenograstim
1 BIS
R-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
Intervention: BCNU
1 BIS
R-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
Intervention: ARA-C
1 BIS
R-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
Intervention: VP-16
1 BIS
R-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
Intervention: ASCT
1 BIS
R-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
Intervention: Ciclofosfamide
1 BIS
R-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
Intervention: Doxorubicina
2
R-MegaCHOP14 x 4 Restaging + R-MegaCHOP x 2
Intervention: Rituximab
2
R-MegaCHOP14 x 4 Restaging + R-MegaCHOP x 2
Intervention: Ciclofosfamide
2
R-MegaCHOP14 x 4 Restaging + R-MegaCHOP x 2
Intervention: Vincristina
2
R-MegaCHOP14 x 4 Restaging + R-MegaCHOP x 2
Intervention: Prednisone
2
R-MegaCHOP14 x 4 Restaging + R-MegaCHOP x 2
Intervention: Pegfilgrastim
2
R-MegaCHOP14 x 4 Restaging + R-MegaCHOP x 2
Intervention: Mitoxantrone
2
R-MegaCHOP14 x 4 Restaging + R-MegaCHOP x 2
Intervention: ARA-C
2 BIS
R-CHOP14 x 4 Restaging + R-CHOP14 x 4
Intervention: Rituximab
2 BIS
R-CHOP14 x 4 Restaging + R-CHOP14 x 4
Intervention: Vincristina
2 BIS
R-CHOP14 x 4 Restaging + R-CHOP14 x 4
Intervention: Ciclofosfamide
2 BIS
R-CHOP14 x 4 Restaging + R-CHOP14 x 4
Intervention: Doxorubicina
Outcomes
Primary Outcomes
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).
Time Frame: 2 years
Secondary Outcomes
- 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)