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

Diffuse Large B-Cell Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00355199
• Other study ID #: EUDRACT: 2005-00700-14
• Status: Completed
• Phase: Phase 3
• First received: July 20, 2006
• Last updated: August 8, 2017
• Start date: May 2005
• Est. completion date: March 2013

Study information

• Verified date: August 2017
• Source: Gruppo Italiano Terapie Innovative nei Linfomi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 246
• Est. completion date: March 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diffuse Large B-Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Rituximab-HDS
Rituximab-HDS
• Rituximab-CHOP
Rituximab-CHOP

Locations

Country	Name	City	State
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

Sponsors (1)

Lead Sponsor	Collaborator
Gruppo Italiano Terapie Innovative nei Linfomi

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event Free Survival	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	36 months from end of therapy
Secondary	Complete Remission	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	Through therapy completion an average of 8 months
Secondary	Disease Free Survival	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	36 months from end of therapy
Secondary	Overall Survival	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	36 months from end of therapy
Secondary	Toxicity	Percentage of participants with at least one reported episode of CTC grade III or IV toxic events	Through therapy completion an average of 8 months
Secondary	Efficacy of R-HDS Conditioning as Salvage Therapy in Patients Non-responders After Four Cycles of R-CHOP 14		Through completion of salvage therapy