Overview

This trial is active, not recruiting.

Conditions diffuse large b-cell lymphoma, ipi≥2
Treatments rituximab, ciclofosfamide, doxorubicina, vincristina, prednisone, pegfilgrastim, mitoxantrone, ara-c, lenograstim, bcnu, vp-16, asct
Phase phase 3
Target CD20
Sponsor Fondazione Italiana Linfomi ONLUS
Collaborator Centro di Riferimento per l'Epidemiologia e la Prev. Oncologica Piemonte
Start date January 2006
End date June 2011
Trial size 399 participants
Trial identifier NCT00499018, EudraCT number 2007-000275-42, IIL-DLCL04

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
R-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
rituximab
375 mg/m2 day 1
ciclofosfamide
1200 mg/m2 day 1
doxorubicina
70 mg/m2 day 1
vincristina
1,4 mg/m2 (max 2 mg) day 1
prednisone
100 mg day g 1-5
pegfilgrastim
6 mg day +1
mitoxantrone
8 mg/m2/days 1-3
ara-c
2000 mg/m2/12h day 1 - 3
lenograstim
5 μg/Kg/days +2
bcnu
300 mg/m2 day -7
ara-c
200 mg/m2/12 days -6,-5,-4,-3
vp-16
100 mg/m2/12h days -6,-5,-4,-3
asct
PBSC Reinfusion
(Experimental)
R-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
rituximab
375 mg/m2 day 1
vincristina
1,4 mg/m2 (max 2 mg) day 1
prednisone
100 mg day g 1-5
pegfilgrastim
6 mg day +1
lenograstim
5 μg/Kg/days +2
bcnu
300 mg/m2 day -7
ara-c
200 mg/m2/12 days -6,-5,-4,-3
vp-16
100 mg/m2/12h days -6,-5,-4,-3
asct
PBSC Reinfusion
ciclofosfamide
750 mg/m2 day 1
doxorubicina
50 mg/m2 day 1
vincristina
1,4 mg/m2 (max 2 mg) day 1
(Experimental)
R-MegaCHOP14 x 4 Restaging + R-MegaCHOP x 2
rituximab
375 mg/m2 day 1
ciclofosfamide
1200 mg/m2 day 1
doxorubicina
70 mg/m2 day 1
vincristina
1,4 mg/m2 (max 2 mg) day 1
prednisone
100 mg day g 1-5
pegfilgrastim
6 mg day +1
mitoxantrone
8 mg/m2/days 1-3
ara-c
2000 mg/m2/12h day 1 - 3
(Experimental)
R-CHOP14 x 4 Restaging + R-CHOP14 x 4
rituximab
375 mg/m2 day 1
vincristina
1,4 mg/m2 (max 2 mg) day 1
prednisone
100 mg day g 1-5
ciclofosfamide
750 mg/m2 day 1
doxorubicina
50 mg/m2 day 1
vincristina
1,4 mg/m2 (max 2 mg) day 1

Primary Outcomes

Measure
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

Measure
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).
time frame: 3 years
To evaluate the efficacy of two different dose-dense + Rituximab chemotherapy regimens in term of 2-years Failure Free Survival (FFS).
time frame: 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).
time frame: 2 years
To evaluate the efficacy of the four different induction arms in terms of 2-years FFS (exploratory analysis).
time frame: 2 years

Eligibility Criteria

Male or female participants from 18 years up to 60 years old.

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

Additional Information

Official title 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.
Principal investigator Umberto Vitolo, MD
Trial information was received from ClinicalTrials.gov and was last updated in February 2011.
Information provided to ClinicalTrials.gov by Fondazione Italiana Linfomi ONLUS.