This is the classic website, which will be retired eventually. Please visit the modernized instead.
Working… Menu

Induction Chemotherapy (R-CHOP Vs. R-FC) Followed by Interferon Maintenance Versus Rituximab Maintenance in MCL (MCLelderly)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00209209
Recruitment Status : Unknown
Verified March 2017 by Prof. Dr. M. Dreyling (co-chairman), European Mantle Cell Lymphoma Network.
Recruitment status was:  Active, not recruiting
First Posted : September 21, 2005
Last Update Posted : March 7, 2017
German Low Grade Lymphoma Study Group
Lymphoma Study Association
HOVON - Dutch Haemato-Oncology Association
Nordic Lymphoma Group
Information provided by (Responsible Party):
Prof. Dr. M. Dreyling (co-chairman), European Mantle Cell Lymphoma Network

Brief Summary:

The aim of this study is to answer the following independent questions in the treatment of mantle cell lymphomas:

  • Can rituximab-fludarabine, cyclophosphamide (R-FC) improve the reduction of lymphoma mass compared to rituximab-cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) and so become a new standard for initial cytoreductive therapy?
  • Can maintenance with rituximab substitute the interferon maintenance and even improve the progression free survival in patients after successful initial cytoreductive therapy?

Condition or disease Intervention/treatment Phase
Lymphoma, Mantle-Cell Drug: Rituximab Drug: Cyclophosphamide Drug: Doxorubicin Drug: Vincristine Drug: Prednisone Drug: Fludarabine Drug: Interferon-alpha Drug: pegylated formula Interferon-alpha 2b Procedure: chemotherapy: R-CHOP Procedure: chemotherapy: R-FC Procedure: Interferon maintenance Procedure: Rituximab maintenance Phase 3

Detailed Description:

This study investigates two independent questions in the treatment of elderly patients with mantle cell lymphomas:

  1. To test in elderly patients with advanced mantle cell lymphoma, whether rituximab plus a combination of fludarabine with cyclophosphamide (6 FC cycles) results in a higher reduction of lymphoma mass measured by the percentage of CR than rituximab combined with the standard chemotherapy scheme (8 CHOP cycles).
  2. To compare maintenance therapy with rituximab with maintenance with interferon-alpha or pegylated interferon for progression free survival, after 2 different regimens of induction chemo-immunotherapy in elderly patients with mantle cell lymphoma.

This study will be performed as a prospective, randomized, open-label multicenter phase III trial. All patients will be randomized for an initial cytoreductive therapy with R-FC or R-CHOP.

The parameter for the comparison of R-FC and R-CHOP will be the percentage of complete remissions after initial cytoreductive therapy. According to the known results of R-FC and R-CHOP in lymphoma therapy, a relevant difference between R-CHOP and R-FC in the overall response rates is not expected. For both therapies an overall response rate of about 90% is expected. Since it is well known that the prognosis of patients who do not reach at least a PR in the initial therapy is very poor, it will be also necessary to control this parameter during the study. If an unexpected relevant difference in the overall response rates is observed during the study, the initial randomisation should be stopped and all patients should be assigned to the superior therapy. In this case the CR rates will not be important for the choice of the initial therapy. If no relevant differences in the overall response rates are observed, a one sided Fisher test will be performed at the end of the recruitment to test whether the rate of CR's after R-FC is significantly improved compared to R-CHOP.

The statistical parameters for controlling the overall response rates and for testing the CR rates are chosen in the following way: The working significance level for all statistical evaluations in this part of the study will be set to alpha=0.05. The expected CR rate after R-CHOP is according to the observations about 50%; a clinical relevant improvement by R-FC would be a CR rate of 65%. Such an improvement should be detected by the one sided Fisher test with a power of about 95%. According to these parameters about 246 observations for each treatment would be necessary. To control the overall response rates, a difference of 85% to 95% will be clinically so relevant that initial randomisation should be terminated with a probability of about 95%. Overall response rates will be controlled by a restricted sequential procedure.

Patients achieving at least a partial remission after R-FC or R-CHOP will be randomised for interferon maintenance versus rituximab maintenance in order to evaluate the impact of maintenance therapy in progression free survival.

The improvement expected by the new maintenance with rituximab for progression free survival can be expressed by reduction of relative risk (rr). Since a risk reduction to 60% was observed for indolent lymphomas by interferon maintenance, this seems to be a clinical relevant improvement for the new maintenance therapy. For a working significance level alpha=0.05 and a power of 95% the number of events (relapse or death) necessary for a two sided fixed sample trial is about 200. During this study the progression free survival in patients after successful initial therapy will be monitored by an equivalent restricted sequential procedure with a maximum number of 240 observation.

In order to evaluate the impact of initial therapy and maintenance therapy on overall survival in this patients, a total follow up of about 15 years for this study is expected.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 570 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Efficacy of Maintenance Therapy With Rituximab After Induction Chemotherapy (R-CHOP vs. R-FC) for Elderly Patients With Mantle Cell Lymphoma Not Suitable for Autologous Stem Cell Transplantation
Actual Study Start Date : January 14, 2004
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
Drug Information available for: Rituximab

Arm Intervention/treatment
Active Comparator: 1
  1. randomisation: R-CHOP
  2. randomisation: IFN maintenance
Drug: Rituximab

Drug: Cyclophosphamide

Drug: Doxorubicin

Drug: Vincristine

Drug: Prednisone

Drug: Interferon-alpha

Drug: pegylated formula Interferon-alpha 2b

Procedure: chemotherapy: R-CHOP

Procedure: Interferon maintenance

Experimental: 2
  1. randomisation: R-FC
  2. randomisation: Rituximab maintnenance
Drug: Rituximab

Drug: Cyclophosphamide

Drug: Fludarabine

Procedure: chemotherapy: R-FC

Procedure: Rituximab maintenance

Primary Outcome Measures :
  1. First randomisation: Reduction of lymphoma mass measured by the complete remission (CR) rate
  2. Second randomisation: progression-free survival after end of initial chemotherapy

Secondary Outcome Measures :
  1. Survival after registration / first randomisation / second randomisation
  2. Survival after start / end of initial therapy
  3. Time to treatment failure after start of initial therapy
  4. Progression free survival after registration / first randomisation / second randomisation
  5. Side-effects of initial therapy
  6. Side-effects of maintenance therapy

Information from the National Library of Medicine

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.

Layout table for eligibility information
Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically proven mantle cell lymphoma according to the World Health Organization (WHO) classification, preferably confirmed by central pathology review before entering the study
  • Clinical stage II, III or IV
  • Previously untreated patients
  • Above the age of 65 years and older or patients at the age between 60 and 65, if not eligible for high dose chemotherapy
  • WHO performance grade 0, 1 or 2
  • Informed consent according to International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use/European Union Good Clinical Practice (ICH/EU GCP) and national/local regulations
  • Measurable disease. If, for example only bone marrow (BM) infiltration, patients can only undergo a second randomization if a CR is obtained.

Exclusion Criteria:

  • WHO performance of 3 or more
  • Known anti-murine antibody (HAMA) reactivity or known hypersensitivity to murine antibodies
  • Leukocytes <2.0x 10^9/l or thrombocytes <100x 10^9/l, unless clearly related to mantle cell lymphoma (MCL) bone marrow infiltration
  • Patients previously treated for lymphoma
  • Patients without measurable lesions; if, for example only bone marrow infiltration, patients may be included, but can only undergo a second randomization in case of a CR
  • Patients with stage I disease
  • Patients with central nervous system involvement
  • Patients with a history of autoimmune hemolytic anaemia or autoimmune thrombocytopenia
  • Patients with serious cardiac disease (uncontrolled arrhythmias, unstable angina, severe congestive heart failure)
  • Patients with serious pulmonary, neurological, endocrinological or other disorder interfering with full dosing of CHOP or FC chemotherapy
  • Liver enzymes >3x normal or bilirubin >2.5x normal (not due to lymphoma)
  • Creatinine >2x normal value, corrected for age and weight (not due to lymphoma)
  • Patients with unresolved hepatitis B or C infection or known HIV positive infection
  • Uncontrolled infection
  • Patients with a serious depression that needed therapy within the last 5 years
  • Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
  • Concomitant or previous malignancies other than basal cell or squamous cell skin cancer, in situ cervical cancer and other cancer for which the patient has been disease-free for at least 5 years

Information from the National Library of Medicine

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 identifier (NCT number): NCT00209209

Layout table for location information
Czech Republic
General University Hospital, 1St Department of Medicine
Praha, Czech Republic, CZ-12808
Nordic Lymphoma Group
Copenhagen, Denmark, DK-2100
Groupe D´Etudes des Lymphomes De l´Adulte (GELA)
Paris, France, F-75743
German Low Grade Study Group (Glsg)
Munich, Germany, D-81377
Ospedale Ferratotto, Divisione Di Ematologia
Catania, Italy, I-95124
HOVON - Dutch Haemato-Oncology Association (HOVON-Datacenter)
Rotterdam, Netherlands, NL-3008 AE
The Maria Sklodowska Memorial, Cancer Center - Inst. of Oncology
Warszawa, Poland, PL-02-781
Sponsors and Collaborators
European Mantle Cell Lymphoma Network
German Low Grade Lymphoma Study Group
Lymphoma Study Association
HOVON - Dutch Haemato-Oncology Association
Nordic Lymphoma Group
Layout table for investigator information
Principal Investigator: Hanneke C. Kluin-Nelemans, PhD University Hospital Groningen, Dept. of Hematology
Study Chair: Martin Dreyling, PhD University Hospital Grosshadern/LMU, Dept. of Medicine III
Additional Information:
Publications of Results:
Publications automatically indexed to this study by Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Prof. Dr. M. Dreyling (co-chairman), Professor of Medicine, European Mantle Cell Lymphoma Network Identifier: NCT00209209    
Other Study ID Numbers: MCL2004-1
First Posted: September 21, 2005    Key Record Dates
Last Update Posted: March 7, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Prof. Dr. M. Dreyling (co-chairman), European Mantle Cell Lymphoma Network:
Lymphoma, Mantle-Cell
Elderly patients
Maintenance therapy
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Interferon alpha-2
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors