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

NCT00137995 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: CORAL
• Study Type: interventional
• Target: 481
• Locations: 10 countries
• Sites: 10

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.

Conditions

Lymphoma, Large-Cell, Diffuse

Keywords

Lymphoma; Chemotherapy; rituximab

Outcome Measures

Primary Outcomes (2)

• MARR (mobilization adjusted response rate)

  3 months

• EFS (event free survival)

  2 years post transplantation

Secondary Outcomes (3)

• Progression rate

  2 years post transplantation

• Overall survival

  2 years post transplantation

• Duration of response

  2 years post transplantation

Study Arms (2)

R-ICE

EXPERIMENTAL

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

Drug: Rituximab; Drug: Etoposide; Drug: Carboplatine; Drug: Ifosfamide + Mesna; Procedure: Autologous Stem Cell Transplantation; Drug: BCNU; Drug: Cytarabine; Drug: Melphalan

R-DHAP

EXPERIMENTAL

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

Drug: Rituximab; Drug: Cisplatine; Drug: Cytosine Arabinoside; Drug: Dexamethasone; Procedure: Autologous Stem Cell Transplantation; Drug: BCNU; Drug: Etoposide; Drug: Cytarabine; Drug: Melphalan

Interventions

Rituximab DRUG

375 mg/m² D-2/D1

Also known as: R

R-DHAP; R-ICE

Etoposide DRUG

100 mg/m² D1-D2-D3

R-ICE

Carboplatine DRUG

max 800mg D2

R-ICE

Ifosfamide + Mesna DRUG

5 g/m² from D2 to D13

R-ICE

Cisplatine DRUG

100 mg/m² from D1 to D13

R-DHAP

Cytosine Arabinoside DRUG

2000 mg/m²/12 h D2 D3

R-DHAP

Dexamethasone DRUG

40 mg From D1 to D4

R-DHAP

Autologous Stem Cell Transplantation PROCEDURE

Also known as: ASCT

R-DHAP; R-ICE

BCNU DRUG

300mg/m² on D-6

Also known as: BICNU

R-DHAP; R-ICE

Cytarabine DRUG

100 mg/m² from D-6 to D-3

R-DHAP; R-ICE

Melphalan DRUG

140 mg/m² on D-2

R-DHAP; R-ICE

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Lymphoma Study Association: lead

Study Sites (10)

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

Australian leukemia and lymphoma group

Sydney, Australia

Location

Groupe d'atude des lymphome de l'adulte

Yvoir, Belgium

Location

Czech Lymphoma study group

Prague, Czechia

Location

Hospital district of south west Finland

Turku, Finland

Location

German high grade non hodgkin's lymphoma group

Hamburg, Germany

Location

Israel Society of Hematology

Tel Litwinsky, Israel

Location

Nordic center

Uppsala, Sweden

Location

Schweirische Arbeitsgruppe fur klinische Krebsforschung

Lausanne, Switzerland

Location

National cancer research institute

London, United Kingdom

Location

Related Publications (6)

• 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 BACKGROUND

• 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.

  PMID: 14739217 BACKGROUND

• 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.

  PMID: 11807147 BACKGROUND

• 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.

  PMID: 9779700 BACKGROUND

• 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.

  PMID: 23091101 DERIVED

• 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.

  PMID: 20660832 DERIVED

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma

Interventions

Rituximab; Etoposide; Carboplatin; Ifosfamide; Mesna; Cytarabine; Dexamethasone; Carmustine; Melphalan

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Coordination Complexes; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Nitrosourea Compounds; Urea; Amides; Nitroso Compounds; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids

Study Officials

• Christian Gisselbrecht

  Lymphoma Study Association

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2005
• First Posted: August 30, 2005
• Study Start: June 1, 2003
• Primary Completion: October 1, 2008
• Study Completion: October 1, 2008
• Last Updated: August 28, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (1); IL (1); FI (1); SE (1); DE (1); CH (1); GB (1); US (1); AU (1); BE (1)