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

Diffuse Large B-Cell Lymphoma Clinical Trial

— DLCL04  

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.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00499018
• Other study ID #: IIL-DLCL04
• Secondary ID: EudraCT number 2
• Status: Active, not recruiting
• Phase: Phase 3
• First received: July 10, 2007
• Last updated: February 14, 2011
• Start date: January 2006
• Est. completion date: September 2013

Study information

• Verified date: February 2011
• Source: Fondazione Italiana Linfomi ONLUS
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 399
• Est. completion date: September 2013
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diffuse Large B-Cell Lymphoma
• IPI=2
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• 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

Procedure:
• ASCT
PBSC Reinfusion

Drug:
• Ciclofosfamide
750 mg/m2 day 1
• Doxorubicina
50 mg/m2 day 1
• Vincristina
1,4 mg/m2 (max 2 mg) day 1

Locations

Country	Name	City	State
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	Spedali Civili	Brescia
Italy	UTMO Ematologia Università Spedali Civili	Brescia
Italy	Stabilimento "Perrino"	Brindisi
Italy	Ospedale di Circolo	Busto Arsizio - VA
Italy	Ospedale Armando Businco	Cagliari
Italy	Università Cattolica del Sacro Cuore	Campobasso
Italy	IRCC	Candiolo (TO)
Italy	Ospedale Pugliese	Catanzaro
Italy	Ospedale Bufalini	Cesena - FC
Italy	Stabilimento Ospedaliero	Ciriè - TO
Italy	Ospedale Generale di Zona	Civitanova Marche (MC)
Italy	Presidio Ospedaliero Annunziata	Cosenza
Italy	Istituti Ospitalieri	Cremona
Italy	Az. Ospedaliero Universitaria Careggi	Firenze
Italy	Stabilimento Forlì	Forlì
Italy	Azienda Universitaria San Martino	Genova
Italy	A.S.L. 9	Ivrea
Italy	Ospedale Felettino	La Spezia
Italy	Istituto Vito Fazzi	Lecce
Italy	Azienda Ospedaliera Papardo	Messina
Italy	Azienda Ospedaliero Universitaria Policlinico Gaetano Martino	Messina
Italy	Ospedale Civile Umberto I	Mestre	Venezia
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	Osp. Calvi, Noale	Mirano	Venezia
Italy	Azienda Ospedaliera Policlinico	Modena
Italy	Ospedale S. Gerardo	Monza
Italy	Università degli Studi Federico II	Napoli
Italy	Ospedale Umberto I - DH Oncoematologico	Nocera Inferiore	Salerno
Italy	Osp. Maggiore Della Carità	Novara
Italy	Ospedale S. Francesco	Nuoro
Italy	Ospedale San Luigi	Orbassano (TO)
Italy	Azienda Ospedaliera	Padova
Italy	Università degli Studi	Parma
Italy	Fond. Maugeri - Centro medico	Pavia
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 delle Croci	Ravenna
Italy	Ospedale Bianchi Melacrino Morelli	Reggio Calabria
Italy	Ospedale Santa Maria Nuova	Reggio Emilia
Italy	Ospedale Oncologico Regionale	Rionero in Vulture (PZ)
Italy	Istituto Regina Elena	Roma
Italy	Ospedale S. Eugenio	Roma
Italy	Policlinico Universitario A. Gemelli	Roma
Italy	Policlinico Universitario Campus Biomedico	Roma
Italy	Università degli Studi di Roma "La Sapienza"	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	Ospedale SS.Annunziata	Sassari
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	Ospedale Generale Prov. Cardinale G. Panico	Tricase (LE)
Italy	Policlinico Universitario	Udine
Italy	Osp. di Circolo e Fondazione Macchi	Varese
Italy	Stabilimento Ospedaliero	Verbania
Italy	Osp. Sant'Andrea Divisioen di Onco-Ematologia	Vercelli

Sponsors (2)

Lead Sponsor	Collaborator
Fondazione Italiana Linfomi ONLUS	Centro di Riferimento per l'Epidemiologia e la Prev. Oncologica Piemonte

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes
Secondary	To evaluate the efficacy of two different dose-dense + Rituximab chemotherapy regimens in term of 2-years Failure Free Survival (FFS).		2 years	Yes
Secondary	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	Yes
Secondary	To evaluate the efficacy of the four different induction arms in terms of 2-years FFS (exploratory analysis).		2 years	Yes