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

August 8, 2017 updated by: Gruppo Italiano Terapie Innovative nei Linfomi

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

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 Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

246

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Ancona, Italy
        • Clinica di Ematologia - Nuovo Ospedale Torrette
      • Bergamo, Italy
        • U.O. Ematologia - Ospedali Riuniti di Bergamo
      • Bolzano, Italy
        • Divisione di Ematologia - Ospedale Centrale di Bolzano
      • Cagliari, Italy
        • CTMO - Ematologia - Ospedale "R. Binaghi"
      • Catania, Italy
        • Divisione di Ematologia - Ospedale Ferrarotto
      • Cuneo, Italy
        • S.C. Ematologia - Azienda Ospedaliera S. Croce e Carle
      • Milano, Italy
        • Divisione Ematologia - Istituto S. Raffaele
      • Milano, Italy
        • Oncologia Medica - Istituto Nazionale dei Tumori
      • Milano, Italy
        • U.O. Ematologia - Istituto Nazionale dei Tumori
      • Padova, Italy
        • Divisione di Ematologia - Azienda Ospedaliera
      • Palermo, Italy
        • Ematologia - Azienda Ospedaliera V. Cervello
      • Pescara, Italy
        • Ematologia Clinica - Ospedale Civile di Pescara
      • Roma, Italy
        • Ematologia e TMO - Ospedale S. Camillo
      • Torino, Italy
        • Divisione Universitaria di Ematologia - Azienda Ospedaliera S. Giovanni Battista (Molinette)
      • Verona, Italy
        • Dipartimento di Medicina Clinica e Sperimentale - Università di Verona
      • Vicenza, Italy
        • Divisione di Ematologia - Presidio Ospedaliero S. Bortolo

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / 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 Names:
  • Rituximab supplemented high-dose sequential chemotherapy.
ACTIVE_COMPARATOR: R-CHOP
Rituximab-CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone).
Drug: Rituximab-CHOP
Rituximab-CHOP
Other Names:
  • Rituximab/Cyclophosph/doxorubic/vincrist/prednis

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
36 months from end of therapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Through therapy completion an average of 8 months
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
36 months from end of therapy
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
36 months from end of therapy
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
Through therapy completion an average of 8 months
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
Through completion of salvage therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gruppo Italiano Terapie Innovative nei Linfomi

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2005

Primary Completion (ACTUAL)

March 1, 2013

Study Completion (ACTUAL)

March 1, 2013

Study Registration Dates

First Submitted

July 20, 2006

First Submitted That Met QC Criteria

July 20, 2006

First Posted (ESTIMATE)

July 21, 2006

Study Record Updates

Last Update Posted (ACTUAL)

August 10, 2017

Last Update Submitted That Met QC Criteria

August 8, 2017

Last Verified

August 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EUDRACT: 2005-00700-14

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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