R-ICE Versus R-DHAP in Patients Aged 18-65 With Relapse Diffuse Large B-cell Lymphoma
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| ClinicalTrials.gov Identifier: NCT00137995 |
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Recruitment Status :
Completed
First Posted : August 30, 2005
Last Update Posted : August 28, 2019
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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 or disease | Intervention/treatment | Phase |
|---|---|---|
| Lymphoma, Large-Cell, Diffuse | Drug: Rituximab Drug: Etoposide Drug: Carboplatine Drug: Ifosfamide + Mesna Drug: Cisplatine Drug: Cytosine Arabinoside Drug: Dexamethasone Procedure: Autologous Stem Cell Transplantation Drug: BCNU Drug: Cytarabine Drug: Melphalan | Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 481 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (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 |
| Study Start Date : | June 2003 |
| Actual Primary Completion Date : | October 2008 |
| Actual Study Completion Date : | October 2008 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: R-ICE
R-ICE + R-BEAM /ASCT Rituximab, Etoposide, Carboplatine, Ifosfamide + Mesna BCNU, Etoposide, Cytarabine, Melphalan Autologous Stem Cell Transplantation
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Drug: Rituximab
375 mg/m² D-2/D1
Other Name: R Drug: Etoposide 100 mg/m² D1-D2-D3 Drug: Carboplatine max 800mg D2 Drug: Ifosfamide + Mesna 5 g/m² from D2 to D13 Procedure: Autologous Stem Cell Transplantation Other Name: ASCT Drug: BCNU 300mg/m² on D-6
Other Name: BICNU Drug: Etoposide 200 mg/m² from D-6 to D-3 Drug: Cytarabine 100 mg/m² from D-6 to D-3 Drug: Melphalan 140 mg/m² on D-2 |
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Experimental: R-DHAP
R-DHAP + R-BEAM /ASCT Rituximab, Cisplatine, Cytosine Arabinoside, Dexamethasone BCNU, Etoposide, Cytarabine, Melphalan Autologous Stem Cell Transplantation
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Drug: Rituximab
375 mg/m² D-2/D1
Other Name: R Drug: Cisplatine 100 mg/m² from D1 to D13 Drug: Cytosine Arabinoside 2000 mg/m²/12 h D2 D3 Drug: Dexamethasone 40 mg From D1 to D4 Procedure: Autologous Stem Cell Transplantation Other Name: ASCT Drug: BCNU 300mg/m² on D-6
Other Name: BICNU Drug: Etoposide 200 mg/m² from D-6 to D-3 Drug: Cytarabine 100 mg/m² from D-6 to D-3 Drug: Melphalan 140 mg/m² on D-2 |
- MARR (mobilization adjusted response rate) [ Time Frame: 3 months ]
- EFS (event free survival) [ Time Frame: 2 years post transplantation ]
- Progression rate [ Time Frame: 2 years post transplantation ]
- Overall survival [ Time Frame: 2 years post transplantation ]
- Duration of response [ Time Frame: 2 years post transplantation ]
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, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00137995
| 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 | |
| Czechia | |
| Czech Lymphoma study group | |
| Praha, Czechia | |
| 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 | |
| Principal Investigator: | Christian Gisselbrecht | Lymphoma Study Association |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Lymphoma Study Association |
| ClinicalTrials.gov Identifier: | NCT00137995 |
| Obsolete Identifiers: | NCT00081146 |
| Other Study ID Numbers: |
CORAL |
| First Posted: | August 30, 2005 Key Record Dates |
| Last Update Posted: | August 28, 2019 |
| Last Verified: | August 2019 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Lymphoma Chemotherapy rituximab |
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Lymphoma Lymphoma, B-Cell Lymphoma, Large B-Cell, Diffuse Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Lymphoma, Non-Hodgkin Cytarabine Dexamethasone Rituximab Etoposide Etoposide phosphate |
Melphalan Ifosfamide Carboplatin Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal Antineoplastic Agents Antineoplastic Agents, Immunological |