Expired Study
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New York, New York 10021


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.


Study summary:

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.


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.


Study is Available At:


Original ID:

CORAL


NCT ID:

NCT00137995


Secondary ID:


Study Acronym:


Brief Title:

R-ICE Versus R-DHAP in Patients Aged 18-65 With Relapse Diffuse Large B-cell Lymphoma


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


Overall Status:

Completed


Study Phase:

Phase 3


Genders:

N/A


Minimum Age:

18 Years


Maximum Age:

65 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

Lymphoma Study Association


Oversight Authority:

France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

2


Number of Groups:

0


Total Enrollment:

481


Enrollment Type:

Actual


Overall Contact Information

Official Name:Christian Gisselbrecht
Principal Investigator
Lymphoma Study Association

Study Dates

Start Date:June 2003
Completion Date:October 2008
Completion Type:Actual
Primary Completion Date:October 2008
Primary Completion Type:Actual
Verification Date:August 2019
Last Changed Date:August 22, 2019
First Received Date:August 25, 2005

Study Outcomes

Outcome Type:Secondary Outcome
Measure:Duration of response
Time Frame:2 years post transplantation
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Overall survival
Time Frame:2 years post transplantation
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Progression rate
Time Frame:2 years post transplantation
Safety Issues:False
Outcome Type:Primary Outcome
Measure:EFS (event free survival)
Time Frame:2 years post transplantation
Safety Issues:False
Outcome Type:Primary Outcome
Measure:MARR (mobilization adjusted response rate)
Time Frame:3 months
Safety Issues:False

Study Interventions

Intervention Type:Drug
Name:Rituximab
Description:375 mg/m² D-2/D1
Arm Name:R-ICE
Other Name:R
Intervention Type:Drug
Name:Etoposide
Description:100 mg/m² D1-D2-D3
Arm Name:R-ICE
Intervention Type:Drug
Name:Carboplatine
Description:max 800mg D2
Arm Name:R-ICE
Intervention Type:Drug
Name:Ifosfamide + Mesna
Description:5 g/m² from D2 to D13
Arm Name:R-ICE
Intervention Type:Drug
Name:Cisplatine
Description:100 mg/m² from D1 to D13
Arm Name:R-DHAP
Intervention Type:Drug
Name:Cytosine Arabinoside
Description:2000 mg/m²/12 h D2 D3
Arm Name:R-DHAP
Intervention Type:Drug
Name:Dexamethasone
Description:40 mg From D1 to D4
Arm Name:R-DHAP
Intervention Type:Procedure
Name:Autologous Stem Cell Transplantation
Arm Name:R-ICE
Other Name:ASCT
Intervention Type:Drug
Name:BCNU
Description:300mg/m² on D-6
Arm Name:R-ICE
Other Name:BICNU
Intervention Type:Drug
Name:Etoposide
Description:200 mg/m² from D-6 to D-3
Arm Name:R-ICE
Intervention Type:Drug
Name:Cytarabine
Description:100 mg/m² from D-6 to D-3
Arm Name:R-ICE
Intervention Type:Drug
Name:Melphalan
Description:140 mg/m² on D-2
Arm Name:R-ICE

Study Arms

Study Arm Type:Experimental
Arm Name:R-ICE
Description:R-ICE + R-BEAM /ASCT Rituximab, Etoposide, Carboplatine, Ifosfamide + Mesna BCNU, Etoposide, Cytarabine, Melphalan Autologous Stem Cell Transplantation
Study Arm Type:Experimental
Arm Name:R-DHAP
Description:R-DHAP + R-BEAM /ASCT Rituximab, Cisplatine, Cytosine Arabinoside, Dexamethasone BCNU, Etoposide, Cytarabine, Melphalan Autologous Stem Cell Transplantation

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:Lymphoma Study Association

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Reference
Citation:Guglielmi C, Gomez F, Philip T, Hagenbeek A, Martelli M, Sebban C, Milpied N, Bron D, Cahn JY, Somers R, Sonneveld P, Gisselbrecht C, Van Der Lelie H, Chauvin F. Time to relapse has prognostic value in patients with aggressive lymphoma enrolled onto the Parma trial. J Clin Oncol. 1998 Oct;16(10):3264-9.
PMID:9779700
Reference Type:Reference
Citation:Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jan 24;346(4):235-42.
PMID:11807147
Reference Type:Reference
Citation:Kewalramani T, Zelenetz AD, Nimer SD, Portlock C, Straus D, Noy A, O'Connor O, Filippa DA, Teruya-Feldstein J, Gencarelli A, Qin J, Waxman A, Yahalom J, Moskowitz CH. Rituximab and ICE as second-line therapy before autologous stem cell transplantation for relapsed or primary refractory diffuse large B-cell lymphoma. Blood. 2004 May 15;103(10):3684-8. Epub 2004 Jan 22.
PMID:14739217
Reference Type:Reference
Citation:Blay J, Gomez F, Sebban C, Bachelot T, Biron P, Guglielmi C, Hagenbeek A, Somers R, Chauvin F, Philip T. The International Prognostic Index correlates to survival in patients with aggressive lymphoma in relapse: analysis of the PARMA trial. Parma Group. Blood. 1998 Nov 15;92(10):3562-8.
PMID:9808548

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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