Trial Title:
Induction Chemotherapy (R-CHOP Vs. R-FC) Followed by Interferon Maintenance Versus Rituximab Maintenance in MCL
NCT ID:
NCT00209209
Condition:
Lymphoma, Mantle-Cell
Conditions: Official terms:
Lymphoma
Lymphoma, Mantle-Cell
Interferons
Interferon-alpha
Interferon alpha-2
Prednisone
Cyclophosphamide
Rituximab
Doxorubicin
Fludarabine
Vincristine
Conditions: Keywords:
Lymphoma, Mantle-Cell
Elderly patients
Chemotherapy
Maintenance therapy
C04.557.386.480.300.725.500
C15.604.515.569.480.300.725.500
C20.683.515.761.480.300.725.500
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Unknown status
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Rituximab
Description:
antibody
Arm group label:
1
Arm group label:
2
Intervention type:
Drug
Intervention name:
Cyclophosphamide
Description:
chemotherapy
Arm group label:
1
Arm group label:
2
Intervention type:
Drug
Intervention name:
Doxorubicin
Description:
chemotherapy
Arm group label:
1
Intervention type:
Drug
Intervention name:
Vincristine
Description:
chemotherapy
Arm group label:
1
Intervention type:
Drug
Intervention name:
Prednisone
Description:
coricosteroide
Arm group label:
1
Intervention type:
Drug
Intervention name:
Fludarabine
Description:
chemotherapy
Arm group label:
2
Intervention type:
Drug
Intervention name:
Interferon-alpha
Description:
cytokine
Arm group label:
1
Intervention type:
Drug
Intervention name:
pegylated formula Interferon-alpha 2b
Description:
cytokine
Arm group label:
1
Intervention type:
Procedure
Intervention name:
chemotherapy: R-CHOP
Description:
immuno-chemotherapy
Arm group label:
1
Intervention type:
Procedure
Intervention name:
chemotherapy: R-FC
Description:
immuno-chemotherapy
Arm group label:
2
Intervention type:
Procedure
Intervention name:
Interferon maintenance
Description:
cytokine
Arm group label:
1
Intervention type:
Procedure
Intervention name:
Rituximab maintenance
Description:
antibody
Arm group label:
2
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?
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.
Criteria for eligibility:
Criteria:
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
Gender:
All
Minimum age:
60 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
General University Hospital, 1St Department of Medicine
Address:
City:
Praha
Zip:
CZ-12808
Country:
Czech Republic
Facility:
Name:
Nordic Lymphoma Group
Address:
City:
Copenhagen
Zip:
DK-2100
Country:
Denmark
Facility:
Name:
Groupe D´Etudes des Lymphomes De l´Adulte (GELA)
Address:
City:
Paris
Zip:
F-75743
Country:
France
Facility:
Name:
German Low Grade Study Group (Glsg)
Address:
City:
Munich
Zip:
D-81377
Country:
Germany
Facility:
Name:
Ospedale Ferratotto, Divisione Di Ematologia
Address:
City:
Catania
Zip:
I-95124
Country:
Italy
Facility:
Name:
HOVON - Dutch Haemato-Oncology Association (HOVON-Datacenter)
Address:
City:
Rotterdam
Zip:
NL-3008 AE
Country:
Netherlands
Facility:
Name:
The Maria Sklodowska Memorial, Cancer Center - Inst. of Oncology
Address:
City:
Warszawa
Zip:
PL-02-781
Country:
Poland
Start date:
January 14, 2004
Completion date:
December 2018
Lead sponsor:
Agency:
European Mantle Cell Lymphoma Network
Agency class:
Other
Collaborator:
Agency:
German Low Grade Lymphoma Study Group
Agency class:
Other
Collaborator:
Agency:
Lymphoma Study Association
Agency class:
Other
Collaborator:
Agency:
HOVON - Dutch Haemato-Oncology Association
Agency class:
Other
Collaborator:
Agency:
Nordic Lymphoma Group
Agency class:
Other
Source:
European Mantle Cell Lymphoma Network
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT00209209
http://www.european-mcl.net
