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

• ClinicalTrials.gov Identifier: NCT00355199
• Recruitment Status: Completed
• First Posted: July 21, 2006
• Results First Posted: August 10, 2017
• Last Update Posted: August 10, 2017
• Sponsor: Gruppo Italiano Terapie Innovative nei Linfomi
• Information provided by (Responsible Party): Gruppo Italiano Terapie Innovative nei Linfomi

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Diffuse Large B-Cell Lymphoma	Drug: Rituximab-HDS; Drug: Rituximab-CHOP	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 246 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: May 2005
• Actual Primary Completion Date: March 2013
• Actual Study Completion Date: March 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: R-HDS; R-HDS : Rituximab supplemented high-dose (Cyclophosphamide,Ara-C, Methotrexate, Etoposide, Cis-Platin) sequential chemotherapy with autografting.	Drug: Rituximab-HDS; Rituximab-HDS; Other Name: Rituximab supplemented high-dose sequential chemotherapy.
Active Comparator: R-CHOP; Rituximab-CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone).	Drug: Rituximab-CHOP; Rituximab-CHOP; Other Name: Rituximab/Cyclophosph/doxorubic/vincrist/prednis

Outcome Measures

Primary Outcome Measures :

1. Event Free Survival [ Time Frame: 36 months from end of therapy ]
   EFS was defined from the time of the study entry to any treatment failure including disease progression or discontinuation of treatment for any reason or date of the last follow-up visit

Secondary Outcome Measures :

1. Complete Remission [ Time Frame: Through therapy completion an average of 8 months ]
   Clinical response was assessed by complete restaging according to Cheson criteria. Cheson BD, Pfistner B, Juweid ME, et al: Revised response criteria for malignant lymphoma. J Clin Oncol 25:579-86, 2007
2. Disease Free Survival [ Time Frame: 36 months from end of therapy ]
   DFS was defined from the time of documentation of CR to time to relapse or death as a result of lymphoma or acute toxicity of treatment or date of the last follow-up visit
3. Overall Survival [ Time Frame: 36 months from end of therapy ]
   OS was defined from the time of the study entry to death as a result of any cause or date of the last follow-up visit
4. Toxicity [ Time Frame: Through therapy completion an average of 8 months ]
   Percentage of participants with at least one reported episode of CTC grade III or IV toxic events
5. Efficacy of R-HDS Conditioning as Salvage Therapy in Patients Non-responders After Four Cycles of R-CHOP 14 [ Time Frame: Through completion of salvage therapy ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

Italy

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

Milano, Italy

Oncologia Medica - Istituto Nazionale dei Tumori

Milano, Italy

U.O. Ematologia - Istituto Nazionale dei Tumori

Milano, Italy

Divisione di Ematologia - Azienda Ospedaliera

Padova, 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

Sponsors and Collaborators

Gruppo Italiano Terapie Innovative nei Linfomi

Investigators

• Study Chair: Sergio Cortelazzo, MD; Divisione di Ematologia - Ospedale Centrale di Bolzano - 39100 Bolzano Italy

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Gruppo Italiano Terapie Innovative nei Linfomi
• ClinicalTrials.gov Identifier: NCT00355199
• Other Study ID Numbers: EUDRACT: 2005-00700-14
• First Posted: July 21, 2006
• Results First Posted: August 10, 2017
• Last Update Posted: August 10, 2017
• Last Verified: August 2017

Keywords provided by Gruppo Italiano Terapie Innovative nei Linfomi:

DLBCL; R-HDS; R-CHOP14

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Large B-Cell, Diffuse; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Rituximab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents