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

NCT ID: NCT00499018

Last Updated: 2011-02-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

399 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-01-31

Study Completion Date

2013-09-30

Brief Summary

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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

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Conditions

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Diffuse Large B-Cell Lymphoma IPI≥2

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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1

R-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT

Group Type EXPERIMENTAL

Rituximab

Intervention Type DRUG

375 mg/m2 day 1

Ciclofosfamide

Intervention Type DRUG

1200 mg/m2 day 1

Doxorubicina

Intervention Type DRUG

70 mg/m2 day 1

Vincristina

Intervention Type DRUG

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

Prednisone

Intervention Type DRUG

100 mg day g 1-5

Pegfilgrastim

Intervention Type DRUG

6 mg day +1

Mitoxantrone

Intervention Type DRUG

8 mg/m2/days 1-3

ARA-C

Intervention Type DRUG

2000 mg/m2/12h day 1 - 3

Lenograstim

Intervention Type DRUG

5 μg/Kg/days +2

BCNU

Intervention Type DRUG

300 mg/m2 day -7

ARA-C

Intervention Type DRUG

200 mg/m2/12 days -6,-5,-4,-3

VP-16

Intervention Type DRUG

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

ASCT

Intervention Type PROCEDURE

PBSC Reinfusion

1 BIS

R-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT

Group Type EXPERIMENTAL

Rituximab

Intervention Type DRUG

375 mg/m2 day 1

Vincristina

Intervention Type DRUG

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

Prednisone

Intervention Type DRUG

100 mg day g 1-5

Pegfilgrastim

Intervention Type DRUG

6 mg day +1

Lenograstim

Intervention Type DRUG

5 μg/Kg/days +2

BCNU

Intervention Type DRUG

300 mg/m2 day -7

ARA-C

Intervention Type DRUG

200 mg/m2/12 days -6,-5,-4,-3

VP-16

Intervention Type DRUG

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

ASCT

Intervention Type PROCEDURE

PBSC Reinfusion

Ciclofosfamide

Intervention Type DRUG

750 mg/m2 day 1

Doxorubicina

Intervention Type DRUG

50 mg/m2 day 1

Vincristina

Intervention Type DRUG

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

2

R-MegaCHOP14 x 4 Restaging + R-MegaCHOP x 2

Group Type EXPERIMENTAL

Rituximab

Intervention Type DRUG

375 mg/m2 day 1

Ciclofosfamide

Intervention Type DRUG

1200 mg/m2 day 1

Doxorubicina

Intervention Type DRUG

70 mg/m2 day 1

Vincristina

Intervention Type DRUG

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

Prednisone

Intervention Type DRUG

100 mg day g 1-5

Pegfilgrastim

Intervention Type DRUG

6 mg day +1

Mitoxantrone

Intervention Type DRUG

8 mg/m2/days 1-3

ARA-C

Intervention Type DRUG

2000 mg/m2/12h day 1 - 3

2 BIS

R-CHOP14 x 4 Restaging + R-CHOP14 x 4

Group Type EXPERIMENTAL

Rituximab

Intervention Type DRUG

375 mg/m2 day 1

Vincristina

Intervention Type DRUG

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

Prednisone

Intervention Type DRUG

100 mg day g 1-5

Ciclofosfamide

Intervention Type DRUG

750 mg/m2 day 1

Doxorubicina

Intervention Type DRUG

50 mg/m2 day 1

Vincristina

Intervention Type DRUG

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

Interventions

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Rituximab

375 mg/m2 day 1

Intervention Type DRUG

Ciclofosfamide

1200 mg/m2 day 1

Intervention Type DRUG

Doxorubicina

70 mg/m2 day 1

Intervention Type DRUG

Vincristina

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

Intervention Type DRUG

Prednisone

100 mg day g 1-5

Intervention Type DRUG

Pegfilgrastim

6 mg day +1

Intervention Type DRUG

Mitoxantrone

8 mg/m2/days 1-3

Intervention Type DRUG

ARA-C

2000 mg/m2/12h day 1 - 3

Intervention Type DRUG

Lenograstim

5 μg/Kg/days +2

Intervention Type DRUG

BCNU

300 mg/m2 day -7

Intervention Type DRUG

ARA-C

200 mg/m2/12 days -6,-5,-4,-3

Intervention Type DRUG

VP-16

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

Intervention Type DRUG

ASCT

PBSC Reinfusion

Intervention Type PROCEDURE

Ciclofosfamide

750 mg/m2 day 1

Intervention Type DRUG

Doxorubicina

50 mg/m2 day 1

Intervention Type DRUG

Vincristina

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

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Centro di Riferimento per l'Epidemiologia e la Prev. Oncologica Piemonte

OTHER

Sponsor Role collaborator

Fondazione Italiana Linfomi - ETS

OTHER

Sponsor Role lead

Responsible Party

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A.O. San Giovanni Battista - Molinette Torino

Principal Investigators

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Umberto Vitolo, MD

Role: PRINCIPAL_INVESTIGATOR

S.C. Ematologia II - OSP.S. GIOV.BATTISTA MOLINETTE - TORINO (TO) -

Locations

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Ospedale Umberto I - DH Oncoematologico

Nocera Inferiore, Salerno, Italy

Site Status

Ospedale Civile Umberto I

Mestre, Venezia, Italy

Site Status

Osp. Calvi, Noale

Mirano, Venezia, Italy

Site Status

Az. Osp. SS. Antonio e Biagio e Cesare Arrigo

Alessandria, , Italy

Site Status

Ospedale Cardinal Massaia

Asti, , Italy

Site Status

Centro di Riferimento Oncologico

Aviano - PN, , Italy

Site Status

Azienda Ospedale Policlinico Consorziale

Bari, , Italy

Site Status

IRCC Istituto tumori Ematologia

Bari, , Italy

Site Status

Osp. Degli Infermi

Biella, , Italy

Site Status

Ospedale Policlinico S. Orsola Malpighi

Bologna, , Italy

Site Status

Spedali Civili

Brescia, , Italy

Site Status

UTMO Ematologia Università Spedali Civili

Brescia, , Italy

Site Status

Stabilimento "Perrino"

Brindisi, , Italy

Site Status

Ospedale di Circolo

Busto Arsizio - VA, , Italy

Site Status

Ospedale Armando Businco

Cagliari, , Italy

Site Status

Università Cattolica del Sacro Cuore

Campobasso, , Italy

Site Status

IRCC

Candiolo (TO), , Italy

Site Status

Ospedale Pugliese

Catanzaro, , Italy

Site Status

Ospedale Bufalini

Cesena - FC, , Italy

Site Status

Stabilimento Ospedaliero

Ciriè - to, , Italy

Site Status

Ospedale Generale di Zona

Civitanova Marche (MC), , Italy

Site Status

Presidio Ospedaliero Annunziata

Cosenza, , Italy

Site Status

Istituti Ospitalieri

Cremona, , Italy

Site Status

Az. Ospedaliero Universitaria Careggi

Florence, , Italy

Site Status

Stabilimento Forlì

Forlì, , Italy

Site Status

Azienda Universitaria San Martino

Genova, , Italy

Site Status

A.S.L. 9

Ivrea, , Italy

Site Status

Ospedale Felettino

La Spezia, , Italy

Site Status

Istituto Vito Fazzi

Lecce, , Italy

Site Status

Azienda Ospedaliera Papardo

Messina, , Italy

Site Status

Azienda Ospedaliero Universitaria Policlinico Gaetano Martino

Messina, , Italy

Site Status

Istituto Europeo di Oncologia

Milan, , Italy

Site Status

Osp. San Carlo Borromeo

Milan, , Italy

Site Status

Ospedale Cà Grande - Niguarda

Milan, , Italy

Site Status

Ospedale Fatebenefratelli

Milan, , Italy

Site Status

Presidio Osp. Maggiore Policlinico

Milan, , Italy

Site Status

Azienda Ospedaliera Policlinico

Modena, , Italy

Site Status

Ospedale S. Gerardo

Monza, , Italy

Site Status

Università degli Studi Federico II

Napoli, , Italy

Site Status

Osp. Maggiore Della Carità

Novara, , Italy

Site Status

Ospedale S. Francesco

Nuoro, , Italy

Site Status

Ospedale San Luigi

Orbassano (TO), , Italy

Site Status

Azienda Ospedaliera

Padua, , Italy

Site Status

Università degli Studi

Parma, , Italy

Site Status

Fond. Maugeri - Centro medico

Pavia, , Italy

Site Status

Ospedale Policlinico San Matteo

Pavia, , Italy

Site Status

Ospedale di Piacenza

Piacenza, , Italy

Site Status

Azienda Ospedaliero Universitaria Pisana

Pisa, , Italy

Site Status

Azienda Ospedaliera Ospedale San Carlo

Potenza, , Italy

Site Status

Ospedale Santa Maria delle Croci

Ravenna, , Italy

Site Status

Ospedale Bianchi Melacrino Morelli

Reggio Calabria, , Italy

Site Status

Ospedale Santa Maria Nuova

Reggio Emilia, , Italy

Site Status

Ospedale Oncologico Regionale

Rionero in Vulture (PZ), , Italy

Site Status

Istituto Regina Elena

Roma, , Italy

Site Status

Ospedale S. Eugenio

Roma, , Italy

Site Status

Policlinico Universitario A. Gemelli

Roma, , Italy

Site Status

Policlinico Universitario Campus Biomedico

Roma, , Italy

Site Status

Università degli Studi di Roma "La Sapienza"

Roma, , Italy

Site Status

Università degli Studi di Roma 'Tor Vergata'

Roma, , Italy

Site Status

Ospedale di Ronciglione

Ronciglione (VT), , Italy

Site Status

Istituto Clinico Humanitas

Rozzano - MI, , Italy

Site Status

Casa Sollievo della Sofferenza

San Giovanni Rotondo (FG), , Italy

Site Status

Ospedale SS.Annunziata

Sassari, , Italy

Site Status

Spedali Riuniti

Siena, , Italy

Site Status

Ospedale Morelli

Sondalo, , Italy

Site Status

Stabilimento SS. Annunziata

Taranto, , Italy

Site Status

Azienda Ospedaliera di Perugia

Terni, , Italy

Site Status

Osp. S. Giovanni Battista "Molinette"

Torino, , Italy

Site Status

Ospedale Ca Focello

Treviso, , Italy

Site Status

Presidio Ospedaliero di Vittorio Veneto

Treviso, , Italy

Site Status

Ospedale Generale Prov. Cardinale G. Panico

Tricase (LE), , Italy

Site Status

Policlinico Universitario

Udine, , Italy

Site Status

Osp. di Circolo e Fondazione Macchi

Varese, , Italy

Site Status

Stabilimento Ospedaliero

Verbania, , Italy

Site Status

Osp. Sant'Andrea Divisioen di Onco-Ematologia

Vercelli, , Italy

Site Status

Countries

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Italy

References

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Derenzini E, Mazzara S, Melle F, Motta G, Fabbri M, Bruna R, Agostinelli C, Cesano A, Corsini CA, Chen N, Righi S, Sabattini E, Chiappella A, Calleri A, Fiori S, Tabanelli V, Cabras A, Pruneri G, Vitolo U, Gianni AM, Rambaldi A, Corradini P, Zinzani PL, Tarella C, Pileri S. A three-gene signature based on MYC, BCL-2 and NFKBIA improves risk stratification in diffuse large B-cell lymphoma. Haematologica. 2021 Sep 1;106(9):2405-2416. doi: 10.3324/haematol.2019.236455.

Reference Type DERIVED
PMID: 32817282 (View on PubMed)

Chiappella A, Martelli M, Angelucci E, Brusamolino E, Evangelista A, Carella AM, Stelitano C, Rossi G, Balzarotti M, Merli F, Gaidano G, Pavone V, Rigacci L, Zaja F, D'Arco A, Cascavilla N, Russo E, Castellino A, Gotti M, Congiu AG, Cabras MG, Tucci A, Agostinelli C, Ciccone G, Pileri SA, Vitolo U. Rituximab-dose-dense chemotherapy with or without high-dose chemotherapy plus autologous stem-cell transplantation in high-risk diffuse large B-cell lymphoma (DLCL04): final results of a multicentre, open-label, randomised, controlled, phase 3 study. Lancet Oncol. 2017 Aug;18(8):1076-1088. doi: 10.1016/S1470-2045(17)30444-8. Epub 2017 Jun 28.

Reference Type DERIVED
PMID: 28668386 (View on PubMed)

Other Identifiers

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EudraCT number 2007-000275-42

Identifier Type: -

Identifier Source: secondary_id

IIL-DLCL04

Identifier Type: -

Identifier Source: org_study_id

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