Comparison of HD Chemotherapy Followed by Auto-transplant and R-CHOP in High Risk Patients With DLBCL.

NCT ID: NCT00355199

Last Updated: 2017-08-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 246 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-05-31
• Study Completion Date: 2013-03-31

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.

Conditions

Diffuse Large B-Cell Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

R-HDS

R-HDS : Rituximab supplemented high-dose (Cyclophosphamide,Ara-C, Methotrexate, Etoposide, Cis-Platin) sequential chemotherapy with autografting.

Group Type: EXPERIMENTAL

Rituximab-HDS

Intervention Type: DRUG

Rituximab-HDS

R-CHOP

Rituximab-CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone).

Group Type: ACTIVE_COMPARATOR

Rituximab-CHOP

Intervention Type: DRUG

Rituximab-CHOP

Interventions

Rituximab-HDS

Rituximab-HDS

Intervention Type: DRUG

Rituximab-CHOP

Rituximab-CHOP

Intervention Type: DRUG

Other Intervention Names

Rituximab supplemented high-dose sequential chemotherapy.; Rituximab/Cyclophosph/doxorubic/vincrist/prednis

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gruppo Italiano Terapie Innovative nei Linfomi

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sergio Cortelazzo, MD

Role: STUDY_CHAIR

Divisione di Ematologia - Ospedale Centrale di Bolzano - 39100 Bolzano Italy

Locations

Clinica di Ematologia - Nuovo Ospedale Torrette

Ancona, , Italy

U.O. Ematologia - Ospedali Riuniti di Bergamo

Bergamo, , Italy

Divisione di Ematologia - Ospedale Centrale di Bolzano

Bolzano, , Italy

CTMO - Ematologia - Ospedale "R. Binaghi"

Cagliari, , Italy

Divisione di Ematologia - Ospedale Ferrarotto

Catania, , Italy

S.C. Ematologia - Azienda Ospedaliera S. Croce e Carle

Cuneo, , Italy

Divisione Ematologia - Istituto S. Raffaele

Milan, , Italy

Oncologia Medica - Istituto Nazionale dei Tumori

Milan, , Italy

U.O. Ematologia - Istituto Nazionale dei Tumori

Milan, , Italy

Divisione di Ematologia - Azienda Ospedaliera

Padua, , Italy

Ematologia - Azienda Ospedaliera V. Cervello

Palermo, , Italy

Ematologia Clinica - Ospedale Civile di Pescara

Pescara, , Italy

Ematologia e TMO - Ospedale S. Camillo

Roma, , Italy

Divisione Universitaria di Ematologia - Azienda Ospedaliera S. Giovanni Battista (Molinette)

Torino, , Italy

Dipartimento di Medicina Clinica e Sperimentale - Università di Verona

Verona, , Italy

Divisione di Ematologia - Presidio Ospedaliero S. Bortolo

Vicenza, , Italy

Countries

Italy

References

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)

Other Identifiers

EUDRACT: 2005-00700-14

Identifier Type: -

Identifier Source: org_study_id