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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00137995




Registration number
NCT00137995
Ethics application status
Date submitted
25/08/2005
Date registered
30/08/2005
Date last updated
28/08/2019

Titles & IDs
Public title
R-ICE Versus R-DHAP in Patients Aged 18-65 With Relapse Diffuse Large B-cell Lymphoma
Scientific 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
Secondary ID [1] 0 0
CORAL
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lymphoma, Large-Cell, Diffuse 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Rituximab
Treatment: Drugs - Etoposide
Treatment: Drugs - Carboplatine
Treatment: Drugs - Ifosfamide + Mesna
Treatment: Drugs - Cisplatine
Treatment: Drugs - Cytosine Arabinoside
Treatment: Drugs - Dexamethasone
Treatment: Drugs - BCNU
Treatment: Drugs - Etoposide
Treatment: Drugs - Cytarabine
Treatment: Drugs - Melphalan

Experimental: R-ICE - R-ICE + R-BEAM /ASCT Rituximab, Etoposide, Carboplatine, Ifosfamide + Mesna BCNU, Etoposide, Cytarabine, Melphalan Autologous Stem Cell Transplantation

Experimental: R-DHAP - R-DHAP + R-BEAM /ASCT Rituximab, Cisplatine, Cytosine Arabinoside, Dexamethasone BCNU, Etoposide, Cytarabine, Melphalan Autologous Stem Cell Transplantation


Treatment: Drugs: Rituximab
375 mg/m² D-2/D1

Treatment: Drugs: Etoposide
100 mg/m² D1-D2-D3

Treatment: Drugs: Carboplatine
max 800mg D2

Treatment: Drugs: Ifosfamide + Mesna
5 g/m² from D2 to D13

Treatment: Drugs: Cisplatine
100 mg/m² from D1 to D13

Treatment: Drugs: Cytosine Arabinoside
2000 mg/m²/12 h D2 D3

Treatment: Drugs: Dexamethasone
40 mg From D1 to D4

Treatment: Drugs: BCNU
300mg/m² on D-6

Treatment: Drugs: Etoposide
200 mg/m² from D-6 to D-3

Treatment: Drugs: Cytarabine
100 mg/m² from D-6 to D-3

Treatment: Drugs: Melphalan
140 mg/m² on D-2
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
MARR (mobilization adjusted response rate)
Timepoint [1] 0 0
3 months
Primary outcome [2] 0 0
EFS (event free survival)
Timepoint [2] 0 0
2 years post transplantation
Secondary outcome [1] 0 0
Progression rate
Timepoint [1] 0 0
2 years post transplantation
Secondary outcome [2] 0 0
Overall survival
Timepoint [2] 0 0
2 years post transplantation
Secondary outcome [3] 0 0
Duration of response
Timepoint [3] 0 0
2 years post transplantation

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/06/2003
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/10/2008
Sample size
Target
Accrual to date
Final
481
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Australian leukemia and lymphoma group - Sydney
Recruitment postcode(s) [1] 0 0
- Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New York
Country [2] 0 0
Belgium
State/province [2] 0 0
Yvoir
Country [3] 0 0
Czechia
State/province [3] 0 0
Praha
Country [4] 0 0
Finland
State/province [4] 0 0
Turku
Country [5] 0 0
Germany
State/province [5] 0 0
Hamburg
Country [6] 0 0
Israel
State/province [6] 0 0
Tel-Hashomer
Country [7] 0 0
Sweden
State/province [7] 0 0
Uppsala
Country [8] 0 0
Switzerland
State/province [8] 0 0
Lausanne
Country [9] 0 0
United Kingdom
State/province [9] 0 0
London

Funding & Sponsors
Primary sponsor type
Other
Name
Lymphoma Study Association
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00137995
Trial related presentations / publications
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.
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. doi: 10.1182/blood-2003-11-3911. Epub 2004 Jan 22.
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. doi: 10.1056/NEJMoa011795.
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. doi: 10.1200/JCO.1998.16.10.3264.
Gisselbrecht C, Schmitz N, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Milpied NJ, Radford J, Ketterer N, Shpilberg O, Duhrsen U, Hagberg H, Ma DD, Viardot A, Lowenthal R, Briere J, Salles G, Moskowitz CH, Glass B. Rituximab maintenance therapy after autologous stem-cell transplantation in patients with relapsed CD20(+) diffuse large B-cell lymphoma: final analysis of the collaborative trial in relapsed aggressive lymphoma. J Clin Oncol. 2012 Dec 20;30(36):4462-9. doi: 10.1200/JCO.2012.41.9416. Epub 2012 Oct 22.
Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Briere J, Moskowitz CH, Schmitz N. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010 Sep 20;28(27):4184-90. doi: 10.1200/JCO.2010.28.1618. Epub 2010 Jul 26. Erratum In: J Clin Oncol. 2012 May 20;30(15):1896.
Public notes

Contacts
Principal investigator
Name 0 0
Christian Gisselbrecht
Address 0 0
Lymphoma Study Association
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00137995