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

Sponsors and Collaborators:	Fondazione Intergruppo Italiano Linfomi Onlus Centro di Riferimento per l'Epidemiologia e la Prev. Oncologica (CPO) Piemonte
Information provided by:	Fondazione Intergruppo Italiano Linfomi Onlus
ClinicalTrials.gov Identifier:	NCT00499018

Purpose

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.

Condition	Intervention	Phase
Diffuse Large B-Cell Lymphoma IPI≥2	Drug: Rituximab Drug: Ciclofosfamide Drug: Doxorubicina Drug: Vincristina Drug: Prednisone Drug: Pegfilgrastim Drug: Mitoxantrone Drug: ARA-C Drug: Lenograstim Drug: BCNU Drug: VP-16 Procedure: ASCT	Phase III

MedlinePlus related topics: Lymphoma

Drug Information available for: Cyclophosphamide Cytarabine Cytarabine hydrochloride Etoposide Mitoxantrone hydrochloride Mitoxantrone Prednisone Rituximab Etoposide phosphate Pegfilgrastim Lenograstim

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Dose Comparison, Parallel Assignment, Safety/Efficacy Study
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.

Further study details as provided by Fondazione Intergruppo Italiano Linfomi Onlus:

Primary Outcome Measures:

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 Outcome Measures:

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 ]

Estimated Enrollment:	376
Study Start Date:	January 2006
Estimated Study Completion Date:	December 2011

Arms	Assigned Interventions
1: Experimental R-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT	Drug: Rituximab 375 mg/m2 day 1 Drug: Ciclofosfamide 1200 mg/m2 day 1 Drug: Doxorubicina 70 mg/m2 day 1 Drug: Vincristina 1,4 mg/m2 (max 2 mg) day 1 Drug: Prednisone 100 mg day g 1-5 Drug: Pegfilgrastim 6 mg day +1 Drug: Mitoxantrone 8 mg/m2/days 1-3 Drug: ARA-C 2000 mg/m2/12h day 1 - 3 Drug: Lenograstim 5 μg/Kg/days +2 Drug: BCNU 300 mg/m2 day -7 Drug: ARA-C 200 mg/m2/12 days -6,-5,-4,-3 Drug: VP-16 100 mg/m2/12h days -6,-5,-4,-3 Procedure: ASCT PBSC Reinfusion
1 BIS: Experimental R-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT	Drug: Rituximab 375 mg/m2 day 1 Drug: Vincristina 1,4 mg/m2 (max 2 mg) day 1 Drug: Prednisone 100 mg day g 1-5 Drug: Pegfilgrastim 6 mg day +1 Drug: Lenograstim 5 μg/Kg/days +2 Drug: BCNU 300 mg/m2 day -7 Drug: ARA-C 200 mg/m2/12 days -6,-5,-4,-3 Drug: VP-16 100 mg/m2/12h days -6,-5,-4,-3 Procedure: ASCT PBSC Reinfusion Drug: Ciclofosfamide 750 mg/m2 day 1 Drug: Doxorubicina 50 mg/m2 day 1 Drug: Vincristina 1,4 mg/m2 (max 2 mg) day 1
2: Experimental R-MegaCHOP14 x 4 Restaging + R-MegaCHOP x 2	Drug: Rituximab 375 mg/m2 day 1 Drug: Ciclofosfamide 1200 mg/m2 day 1 Drug: Doxorubicina 70 mg/m2 day 1 Drug: Vincristina 1,4 mg/m2 (max 2 mg) day 1 Drug: Prednisone 100 mg day g 1-5 Drug: Pegfilgrastim 6 mg day +1 Drug: Mitoxantrone 8 mg/m2/days 1-3 Drug: ARA-C 2000 mg/m2/12h day 1 - 3
2 BIS: Experimental R-CHOP14 x 4 Restaging + R-CHOP14 x 4	Drug: Rituximab 375 mg/m2 day 1 Drug: Vincristina 1,4 mg/m2 (max 2 mg) day 1 Drug: Prednisone 100 mg day g 1-5 Drug: Ciclofosfamide 750 mg/m2 day 1 Drug: Doxorubicina 50 mg/m2 day 1 Drug: Vincristina 1,4 mg/m2 (max 2 mg) day 1

Eligibility

Ages Eligible for Study:	18 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age 18-60;
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 2-3.
ECOG performance status 0-2.
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.
Negative pregnancy test.
Written Informed Consent.

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00499018

Contacts

Contact: Sonia Perticone, PhD	00390131206129	segreteria@iilinf.it
Contact: Daniela Gioia, PhD	00390131206156	segreteria@iilinf.it

Show 83 Study Locations

Sponsors and Collaborators

Fondazione Intergruppo Italiano Linfomi Onlus

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

Investigators

Principal Investigator:

Umberto Vitolo, MD

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

More Information

Study ID Numbers:	IIL-DLCL04, EudraCT number 2007-000275-42
Study First Received:	July 10, 2007
Last Updated:	November 8, 2007
ClinicalTrials.gov Identifier:	NCT00499018
Health Authority:	Italy: National Monitoring Centre for Clinical Trials - Ministry of Health

Keywords provided by Fondazione Intergruppo Italiano Linfomi Onlus:

Large B-Cell Lymphoma
Rituximab
Autologous Stem Cell Transplantation

Study placed in the following topic categories:

Prednisone
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Rituximab
Lenograstim
Cyclophosphamide
Etoposide phosphate
Lymphoma, B-Cell
Lymphoma, large-cell

Lymphatic Diseases
B-cell lymphomas
Mitoxantrone
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin
Etoposide
Lymphoma
Cytarabine

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Hormones
Sensory System Agents
Therapeutic Uses
Analgesics
Alkylating Agents

Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Immune System Diseases
Adjuvants, Immunologic
Immunosuppressive Agents
Antiviral Agents
Glucocorticoids
Pharmacologic Actions
Neoplasms
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Peripheral Nervous System Agents
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009