Clinical trial NCT00355199: Comparison of HD Chemotherapy Followed by Auto-transplant and R-CHOP in High Risk Patients With DLBCL.
Official title: Multicentric Randomized Phase III Study Comparing High Doses of Chemotherapy With Rituximab Followed by Auto-transplant HPC Versus CHOP Plus Rituximab as First Line Therapy in High Risk Patients With DLBCL Non-Hodgkin's Lymphomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diffuse Large B-Cell Lymphoma
Keywords: DLBCL
R-HDS
R-CHOP14
Lead sponsor: Gruppo Italiano Terapie Innovative nei Linfomi
Sponsor class: OTHER
First posted: 2006-07-21
Enrollment: 246
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Multicentric randomized phase III study comparing high doses of chemotherapy with Rituximab followed by auto-transplant HPC versus CHOP plus Rituximab as first line therapy in high risk patients with DLBCL Non-Hodgkin's lymphomas.

Detailed description: Diffuse large B cells Non-Hodgkin's lymphomas represents one of the most frequent form of lymphoma. Its clinical development progresses rapidly and is characterized by a biphasic survival curve with patients in complete remission (which can be considered cured) and patients that relapse. This last group of subjects have only 25%-33% chance of long free disease survival if treated with a second line therapy with high dose chemotherapy plus autologous transplant of PBPC.

Therefore in order to achieve an improvement of the overall survival in patient with DLBCL, it is necessary to increase the number of complete remission after first line therapy.

The aim of R-HDS study, multicentre randomized phase III trial, is to evaluate and compare the efficacy and safety of an intensive conditioning regimen with high intensity chemo-immunotherapy (R-HDS) plus autologous transplantation versus CHOP conditioning regimen plus Rituximab in patients with unfavorable prognosis at diagnosis.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of DLBCL CD20+.
* Patients with Ann Arbor classification B-bulk \>= II
* Patients of age between 18-65 with age-adjusted IPI 2-3 and ECOG performance status 0-3 or patients of age 61-65 with IPI 3, 4, 5 and ECOG performance status 0-2. The disease stage criteria must be documented with instrumental examinations and bone marrow biopsy.
* Hematology parameters one week before starting study as follows: Hb \>= 9 g/dl, WBC \>= 3 x 10exp9/l, neutrophils \>= 1.5 x 10exp9/l, PLT \>= 100 x 10exp9/l.
* Patients with pulmonary DLCO \>= 50% and cardiac EF \>= 40%.
* Voluntary written informed consent must be signed before recruitment, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care. Patients must to be informed on the risk of sterility and they must agree to use contraception for the duration of the study. Male subject have to the opportunity of freezing seminal fluid.

Exclusion Criteria:

* Diagnosis different from that describe above.
* Patients with concomitant, serious and uncontrolled illnesses such as cardiopathies (i.e. congestive cardiopathy, ischemic hearth disease, cardiac arrhythmia not controlled by therapy, IMA in the last six months, hearth disease NYHA class III or IV), hepatopathy not related to the lymphoma (bilirubin \>= 2 mg/dl, ALT \>= 2.5 times the normal value, alkaline phosphatase \>=2.5 times the upper limit), kidneys insufficiency not related to the lymphoma (creatinine \>=2 mg/dl).
* Patients affected by opportunistic infections or with positive serology for HIV, HCV, HbsAg (cases with normal levels of hepatic enzymes and not showing active viral replication documented with HBV-DNA are not excluded from randomization; patients with HBV+ can be enrolled after receiving prophylaxis with lamivudina one week before starting chemotherapy. These patients should be monitored twice a month for HbsAg, HBCab, HBV-DNA).
* Patients which have or have had another type of cancer exception made for skin cancers (melanoma and "in situ" cervical cancer not included).
* Patient with a history of anaphylaxes or more generally patients which have had any serious allergic reaction after serum infusion.
* Patient with uncontrolled epilepsy, CNS disorders or psychiatric problems which, according to the investigator, is likely to interfere with participation in this clinical study (i.e. the signing of the informed consent, therapy compliance).
* Inability to attend follow-up visits.

Primary outcomes:
measure: Event Free Survival
timeFrame: 36 months from end of therapy
Secondary outcomes:
measure: Complete Remission
timeFrame: Through therapy completion an average of 8 months
measure: Disease Free Survival
timeFrame: 36 months from end of therapy
measure: Overall Survival
timeFrame: 36 months from end of therapy
measure: Toxicity
timeFrame: Through therapy completion an average of 8 months
measure: Efficacy of R-HDS Conditioning as Salvage Therapy in Patients Non-responders After Four Cycles of R-CHOP 14
timeFrame: Through completion of salvage therapy
Other outcomes:
Locations:
city: Ancona
country: Italy
facility: Clinica di Ematologia - Nuovo Ospedale Torrette
city: Bergamo
country: Italy
facility: U.O. Ematologia - Ospedali Riuniti di Bergamo
city: Bolzano
country: Italy
facility: Divisione di Ematologia - Ospedale Centrale di Bolzano
city: Cagliari
country: Italy
facility: CTMO - Ematologia - Ospedale "R. Binaghi"
city: Catania
country: Italy
facility: Divisione di Ematologia - Ospedale Ferrarotto
city: Cuneo
country: Italy
facility: S.C. Ematologia - Azienda Ospedaliera S. Croce e Carle
city: Milano
country: Italy
facility: Divisione Ematologia - Istituto S. Raffaele
city: Milano
country: Italy
facility: Oncologia Medica - Istituto Nazionale dei Tumori
city: Milano
country: Italy
facility: U.O. Ematologia - Istituto Nazionale dei Tumori
city: Padova
country: Italy
facility: Divisione di Ematologia - Azienda Ospedaliera
city: Palermo
country: Italy
facility: Ematologia - Azienda Ospedaliera V. Cervello
city: Pescara
country: Italy
facility: Ematologia Clinica - Ospedale Civile di Pescara
city: Roma
country: Italy
facility: Ematologia e TMO - Ospedale S. Camillo
city: Torino
country: Italy
facility: Divisione Universitaria di Ematologia - Azienda Ospedaliera S. Giovanni Battista (Molinette)
city: Verona
country: Italy
facility: Dipartimento di Medicina Clinica e Sperimentale - Università di Verona
city: Vicenza
country: Italy
facility: Divisione di Ematologia - Presidio Ospedaliero S. Bortolo
Study officials:
affiliation: Divisione di Ematologia - Ospedale Centrale di Bolzano - 39100 Bolzano Italy
name: Sergio Cortelazzo, MD
role: STUDY_CHAIR
References:
citation: 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.