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

Registration Number
NCT00499018
Lead Sponsor
Fondazione Italiana Linfomi - ETS
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
399
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

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
2PegfilgrastimR-MegaCHOP14 x 4 Restaging + R-MegaCHOP x 2
1ARA-CR-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
1LenograstimR-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
1ASCTR-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
1 BISVincristinaR-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
1 BISASCTR-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
2 BISPrednisoneR-CHOP14 x 4 Restaging + R-CHOP14 x 4
1VincristinaR-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
1RituximabR-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
1MitoxantroneR-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
1CiclofosfamideR-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
1DoxorubicinaR-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
1PegfilgrastimR-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
1PrednisoneR-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
1BCNUR-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
1VP-16R-MegaCHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
1 BISRituximabR-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
1 BISPrednisoneR-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
1 BISPegfilgrastimR-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
1 BISARA-CR-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
1 BISBCNUR-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
1 BISVP-16R-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
2RituximabR-MegaCHOP14 x 4 Restaging + R-MegaCHOP x 2
1 BISCiclofosfamideR-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
1 BISDoxorubicinaR-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
2CiclofosfamideR-MegaCHOP14 x 4 Restaging + R-MegaCHOP x 2
2DoxorubicinaR-MegaCHOP14 x 4 Restaging + R-MegaCHOP x 2
2VincristinaR-MegaCHOP14 x 4 Restaging + R-MegaCHOP x 2
2PrednisoneR-MegaCHOP14 x 4 Restaging + R-MegaCHOP x 2
2MitoxantroneR-MegaCHOP14 x 4 Restaging + R-MegaCHOP x 2
2ARA-CR-MegaCHOP14 x 4 Restaging + R-MegaCHOP x 2
2 BISRituximabR-CHOP14 x 4 Restaging + R-CHOP14 x 4
2 BISVincristinaR-CHOP14 x 4 Restaging + R-CHOP14 x 4
2 BISCiclofosfamideR-CHOP14 x 4 Restaging + R-CHOP14 x 4
2 BISDoxorubicinaR-CHOP14 x 4 Restaging + R-CHOP14 x 4
1 BISLenograstimR-CHOP14 x 4 Restaging + R-MAD + MAD + BEAM + ASCT
Primary Outcome Measures
NameTimeMethod
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 Outcome Measures
NameTimeMethod
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 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 the four different induction arms in terms of 2-years FFS (exploratory analysis).2 years
To evaluate the efficacy of two different dose-dense + Rituximab chemotherapy regimens in term of 2-years Failure Free Survival (FFS).2 years

Trial Locations

Locations (74)

Ospedale Umberto I - DH Oncoematologico

🇮🇹

Nocera Inferiore, Salerno, Italy

Ospedale Civile Umberto I

🇮🇹

Mestre, Venezia, Italy

Osp. Calvi, Noale

🇮🇹

Mirano, Venezia, 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

Scroll for more (64 remaining)
Ospedale Umberto I - DH Oncoematologico
🇮🇹Nocera Inferiore, Salerno, Italy

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