Dose Dense Chemotherapy + Rituximab +/-Intensified High Dose Chemoimmunotherapy With Support of Peripheral Autologous Stem Cell in Diffuse Large B-Cell Lymphoma

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.

Status

UNKNOWN

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00499018

Acronym

DLCL04

Enrollment

399

Registered

2007-07-11

Start date

2006-01-31

Completion date

2013-09-30

Last updated

2011-02-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diffuse Large B-Cell Lymphoma, IPI≥2

Keywords

Large B-Cell Lymphoma, Rituximab, Autologous Stem Cell Transplantation

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.

Interventions

DRUGRituximab

375 mg/m2 day 1

DRUGCiclofosfamide

1200 mg/m2 day 1

DRUGDoxorubicina

70 mg/m2 day 1

DRUGVincristina

1,4 mg/m2 (max 2 mg) day 1

DRUGPrednisone

100 mg day g 1-5

DRUGPegfilgrastim

6 mg day +1

DRUGMitoxantrone

8 mg/m2/days 1-3

DRUGARA-C

2000 mg/m2/12h day 1 - 3

DRUGLenograstim

5 μg/Kg/days +2

DRUGBCNU

300 mg/m2 day -7

DRUGVP-16

100 mg/m2/12h days -6,-5,-4,-3

PROCEDUREASCT

PBSC Reinfusion

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 60 Years

Healthy volunteers

Inclusion criteria

1. Age 18-60; 2. 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. 3. Advanced stage II, stage III and stage IV with at least two aa-IPI risk factors. 4. Age-adjusted IPI 2-3. 5. ECOG performance status 0-2. 6. LVEF\>45%, measured with echocardiography. 7. Normal hepatic, renal and pulmonary functions. 8. HIV, HCV and HBV negativity. 9. HCV+ admitted only in histologically confirmed absence of replication marks. 10. Positive serology for HBV (occult carriers: AntiHBcAg+, HbsAg-, AntiHBsAg+/-) admitted only upon negativity of weakly positive HBV-DNA test. 11. Life expectancy \> 3 months. 12. Negative pregnancy test. 13. Written Informed Consent.

Exclusion criteria

1. 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. 2. Age \> 60 3. Stage I disease 4. Age-adjusted IPI 0-1 5. ECOG-PS\>3, if not related to Lymphoma 6. Renal impairment (creatinine\>1,2 mg/dl or creatinine clearance \< 60ml/min) 7. Hepatic impairment (AST/ALT or bilirubin \> 2,5 times normal limit, unless due to Lymphoma) 8. HIV positive patients and/or with HBV or HCV active infection(documented by HBV-DNA and HCV-RNA positive tests) 9. 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 10. LFEV\<45% 11. Severe diabetes mellitus difficult to control with adequate insulin therapy 12. Severe chronic obstructive pulmonary disease with hypoxemia 13. Active bacterial, viral of fungal infection requiring systemic therapy 14. Concurrent thrombohemolytic disease 15. HIV positivity 16. HBV positivity 17. Positive serology for HBV (occult carriers: AntiHBc+, HbsAg-, AntiHbs+/-) with positive HBV-DNA test 18. HCV positivity in presence of replication marks (HCV+, CRP+, AST 1,5-2 times normal ranges) 19. CNS localization of disease 20. 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 21. Pregnancy or breast-feeding women 22. Inability of the patient to give her/his informed consent 23. Known hypersensitivity or anaphylactic reaction to murine antibodies or proteins

Design outcomes

Primary

Measure	Time frame
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

Measure	Time frame
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

Countries

Italy

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Mar 9, 2026