R-ICE (ICE Plus Rituximab) Versus R-DHAP (DHAP Plus Rituximab) in Patients Aged 18-65 With Relapse Diffuse Large B-Cell Lymphoma

This study has been completed.
Sponsor:
Information provided by:
Lymphoma Study Association
ClinicalTrials.gov Identifier:
NCT00137995
First received: August 25, 2005
Last updated: January 27, 2009
Last verified: January 2009
  Purpose

The primary objective of this study is to evaluate the efficacy and safety of induction therapy R-ICE in comparison to R-DHAP after 3 cycles adjusted to successful mobilization of stem cells in patients with previously treated diffuse large B-cell lymphoma CD20.

The goal is to detect a difference in mobilization adjusted response rate of 15% between R-ICE and R-DHAP.

The other objective is to evaluate the efficacy and safety of MabThera maintenance therapy after transplantation as measured by the event free survival.

The goal is to obtain a 15% increase of event free survival at 2 years.


Condition Intervention Phase
Lymphoma, Large-Cell, Diffuse
Drug: DHAP plus rituximab
Drug: ICE plus rituximab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Study of ICE Plus RITUXIMAB Versus DHAP Plus Rituximab in Previously Treated Patients With Diffuse Large B-Cell Lymphoma, Followed by Randomized Maintenance With Rituximab

Resource links provided by NLM:


Further study details as provided by Lymphoma Study Association:

Primary Outcome Measures:
  • MARR (mobilization adjusted response rate) and EFS (event free survival)

Secondary Outcome Measures:
  • Progression rate
  • Overall survival
  • Duration of response

Estimated Enrollment: 400
Study Start Date: June 2003
Study Completion Date: October 2008
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Detailed Description:

In vitro, the addition of rituximab to standard anticancer drugs increases cell lyses even in chemoresistant cell lines. This chemosensitization effect was also demonstrated in vivo by the results of the GELA trial in elderly patients with DLCL. Reported phase II study results on the RICE regimen for treatment of patients with relapsed DLCL and comparison with historical controls being treated with ICE suggests that this effect (15% improvement in response rate) is likely in relapsing DLCL and had led the SWOG to stop a randomized trial comparing ICE vs RICE in patients with relapsed aggressive lymphoma.

In the setting of relapsed DLCL, high dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) remains the standard to improve survival in highly selected chemosensitive patients. In the Parma study, only 58% of the patients with relapsed aggressive NHL were good responders after DHAP and 24% were in complete remission. Moreover, the quality of response depended on prognostic factors such as IPI and relapse > 12 months after treatment, and only patients responding to salvage therapy benefited from HDT + ASCT. As shown in the PARMA study. The goal in relapsed DLCL is to improve complete response rates before transplantation as it is the main parameter for eligibility for HDT + ASCT and the main prognostic factor. Unlike first line treatment with CHOP, no standard chemotherapy exists for relapsing patients. DHAP has been the most frequently used regimen for decades but incorporates only two drugs, and has dose-limiting renal toxicity. The ICE regimen was developed at several dosages and studies consistently produced CR rates that were 10-15% superior to DHAP. It is expected that this difference will remain the same with the addition of rituximab to both regimens. Recent phase II data in patients with relapsed DLCL not previously treated with rituximab showed that RICE produced a response rate of 78% with a complete remission rate of 58% and was active in primary refractory disease as well as in intermediate-high risk patients (IPI 2-3). Association of DHAP to Rituximab, R-DHAP has been done on small series of patients by investigators, including patients relapsing after autotransplant. Despite numerous phase II studies, no randomized study has been performed comparing the two regimens (DHAP/ICE) or others in relapsing DLCL. Treatment of first line DLCL has been changed in the past 10 years with more intensive regimens, often followed by ASCT, and very recently with the addition of rituximab to chemotherapy and therefore the population of relapsing patients might be different from the one in the initial PARMA study. A large lymphoma intergroup study working on a large prospective data base might help to find the best salvage regimen and to assess the role of retreatment with monoclonal antibodies in these patients. Finally, the role of rituximab maintenance therapy after HDT + ASCT in prolonging second complete response should be evaluated.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with CD20-positive diffuse large B-cell lymphoma. Disease must be histologically proven in case of relapse or partial response.
  • Aged 18 to 65 years
  • First relapse after complete remission (CR), less than partial remission (PR) or partial response to first line treatment not achieving documented or confirmed complete remission.
  • Eligible for transplant
  • Previously treated with chemotherapy regimen containing anthracyclines with or without rituximab.
  • ECOG performance status 0 to 2.
  • Minimum life expectancy of 3 months.
  • Signed written informed consent prior to randomization.

Exclusion Criteria:

  • Burkitt, mantle-cell and T-cell lymphoma.
  • CD20-negative diffuse large cell lymphoma
  • Documented infection with HIV and hepatitis B virus [HBV] (in the absence of vaccination)
  • Central nervous system or meningeal involvement by lymphoma.
  • Not previously treated with anthracycline-containing regimens
  • Prior transplantation
  • Contra-indication to any drug contained in the chemotherapy regimens.
  • Any serious active disease or co-morbid condition (according to the investigator's decision and information provided in the Investigational Drug Brochure [IDB]).
  • Poor renal function (creatinine level > 150µmol/l or 1.5-2.0 x upper limit of normal [ULN]); poor hepatic function (total bilirubin level > 30mmol/l [> 1.5 x ULN], transaminases > 2.5 maximum normal level) unless these abnormalities are related to the lymphoma; poor bone marrow reserve as defined by neutrophils < 1.5G/l or platelets < 100G/l, unless related to bone marrow infiltration.
  • Any history of cancer during the last 5 years with the exception of non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma.
  • Treatment with any investigational drug within 30 days before planned first cycle of chemotherapy and during the study.
  • Pregnant women
  • Adult patients unable to provide informed consent because of intellectual impairment.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00137995

Locations
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10021
Australia
Australian leukemia and lymphoma group
Sydney, Australia
Belgium
Groupe d'atude des lymphome de l'adulte
Yvoir, Belgium
Czech Republic
Czech Lymphoma study group
Praha, Czech Republic
Finland
Hospital district of south west Finland
Turku, Finland
Germany
German high grade non hodgkin's lymphoma group
Hamburg, Germany
Israel
Israel Society of Hematology
Tel-Hashomer, Israel
Sweden
Nordic center
Uppsala, Sweden
Switzerland
Schweirische Arbeitsgruppe fur klinische Krebsforschung
Lausanne, Switzerland
United Kingdom
National cancer research institute
London, United Kingdom
Sponsors and Collaborators
Lymphoma Study Association
Investigators
Principal Investigator: Christian Gisselbrecht Lymphoma Study Association
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00137995     History of Changes
Obsolete Identifiers: NCT00081146
Other Study ID Numbers: CORAL
Study First Received: August 25, 2005
Last Updated: January 27, 2009
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Lymphoma Study Association:
Lymphoma
Chemotherapy
rituximab

Additional relevant MeSH terms:
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on September 16, 2014