Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

B-cell Lymphoma

Antineoplastic Agents

Analgesics

All Drugs and Chemicals

Antirheumatic Agents

Mitoxantrone

Fludarabine

Fludarabine phosphate

Rituximab

Antineoplastic Agents, Immunological

Immunologic Factors

Rituximab 375 mg/m2 i.v. every 2 months for 24 months

Michael Fridirk, MD

Ulrich Jäger

Immunotherapy with the monoclonal anti-CD20 antibody rituximab has become standard of care for patients with follicular lymphoma. However, there are still open questions regarding dosing and scheduling of rituximab, optimal type of chemotherapeutic combination partners during induction as well as the best interval and length of rituximab maintenance treatment. Fludarabine-mitoxantrone combinations have shown strong debulking activity as initial therapy followed by rituximab maintenance. While rituximab maintenance with a standard dose of 375 mg/m2 prolongs clinical remissions, administration schedules still vary: Three-monthly infusions for 2 years and two-monthly infusions for one or 2 years are most frequently used. A few pharmacokinetic data for rituximab have been reported for induction treatment. These studies have proposed a presumptive "active" level of 25.000 ng/ml in anti-lymphoma treatment. However, there is only limited information regarding maintenance treatment in patients who are in remission and have no remaining tumor load.

The aim of this trial is to investigate the effect of treatment with oral Fludarabine, Mitoxantrone und Rituximab and Rituximab maintenance on the depth of remission measured by BCL2/IgH PCR.

Combination of Oral Fludarabine, Mitoxantrone Und Rituximab Induction Therapy and Rituximab Maintenance Therapy in Follicular B-Cell Lymphoma

Multicenter Study to Evaluate the Combination of Oral Fludarabine, Mitoxantrone Und Rituximab Induction Therapy Und Rituximab Maintenance Therapy in Follicular B-Cell Lymphoma

Arbeitsgemeinschaft medikamentoese Tumortherapie

Lymphoma, Mantle-Cell

Lymphoma, Non-Hodgkin

Mantle Cell Lymphoma

Anti-Inflammatory Agents

Anti-Infective Agents

Antibodies

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Prednisone

Vincristine

Immunoglobulins

Interferons

Interferon-alpha

Interferon alpha-2

Immunosuppressive Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Antiviral Agents

Tubulin Modulators

Antimitotic Agents

1. randomisation: R-CHOP
2. randomisation: IFN maintenance

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

pegylated formula Interferon-alpha 2b

chemotherapy: R-CHOP

chemotherapy: R-FC

Interferon maintenance

Rituximab maintenance

Hanneke C. Kluin-Nelemans, PhD

Martin Dreyling, PhD

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?

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.

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

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Combination of Oral Fludarabine, Mitoxantrone Und Rituximab Induction Therapy and Rituximab Maintenance Therapy in Follicular B-Cell Lymphoma	NCT01560117	Follicular T-NH... Rituximab Maint...	Rituximab	18 Years -	Arbeitsgemeinschaft medikamentoese Tumortherapie
Induction Chemotherapy (R-CHOP Vs. R-FC) Followed by Interferon Maintenance Versus Rituximab Maintenance in MCL	NCT00209209	Lymphoma, Mantl...	Rituximab Cyclophosphamid... Doxorubicin Vincristine Prednisone Fludarabine Interferon-alph... pegylated formu... chemotherapy: R... chemotherapy: R... Interferon main... Rituximab maint...	60 Years -	European Mantle Cell Lymphoma Network

Spots Global Cancer Trial Database for rituximab maintenance