Clinical trial NCT00317096: FCM Versus R-FCM Followed by R-Maintenance or Observation Only
Official title: Treatment of Relapsed CBCC, CC and LPIC Lymphoma With FCM Chemotherapy Alone or in Combination With the Monoclonal Anti CD 20 Antibody Rituximab Followed by Anti-CD 20 Maintenance or Observation Only
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Lymphoma, Follicular
Lymphoma, Low-Grade
Lymphoma, Intermediate-Grade
Keywords: Drug Therapy
Maintenance
rituximab
Lead sponsor: Ludwig-Maximilians - University of Munich
Sponsor class: OTHER
First posted: 2006-04-24
Enrollment: 319
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: The aim of this phase III trial is to assess the safety and efficacy of treatment with rituximab in combination with FCM chemotherapy (R-FCM) versus FCM chemotherapy alone for remission induction and to asses the safety and efficacy of rituximab maintenance versus observation only after response to induction therapy. Both questions are addressed in way of a prospective randomized comparison in patients with relapsed FL, MCL and LP lymphoma.

Detailed description: Patients with relapsed centroblastic/centrocytic (FL), centrocytic (MCL)or lymphoplasmacytoid lymphoma are randomly assigned to either FCM chemotherapy alone or to FCM chemotherapy in combination with the monoclonal anti-CD20 antibody rituximab (R-FCM). FCM chemotherapy will be given for 4 cycles in intervals of 4 weeks.

In patients assigned to cytoreductive therapy with FCM plus rituximab, the monoclonal antibody is given as one infusion (375 mg/m2) on the day before the respective FCM course for a total of four applications.

Four weeks after the end of FCM chemotherapy patients with CR or PR are randomly assigned to either no further treatment or maintenance therapy with rituximab. Rituximab will be given 4 times (one infusion per week with 375 mg/m2). After six months rituximab treatment will be repeated with another 4 infusions.

In case of relapse patients will receive an alternative treatment according to the decision of the investigator.

The aim of this phase III trial is to assess the safety and efficacy of treatment with rituximab in combination with FCM chemotherapy versus FCM chemotherapy alone for remission induction and to asses the safety and efficacy of rituximab maintenance versus observation only after response to induction therapy. Both questions are addressed in way of a prospective randomized comparison in patients with relapsed FCL, MCL and LP lymphoma.

Primary objectives of this trial are to compare (1) the remission rates (CR and PR) achieved after FCM plus rituximab versus FCM alone and (2) the progression free interval of rituximab maintenance versus observation only.

Eligibility criteria: Inclusion Criteria

* patients with histologically proven stage III/IV centroblastic/centrocytic (FL), centrocytic (MCL)or lymphoplasmacytoid lymphoma (LPIC).
* relapsed disease after initial chemotherapy or peripheral blood stem cell transplantation
* two-dimensionally measurable lesion outside a previously irradiated area (osteoblastic bone lesions, ascites, and pleural effusions are not evaluable)
* age \> 18 years
* Karnofsky-index \> 60
* life expectancy of at least 3 months
* effective contraception in female premenopausal patients
* patient's written informed consent

Exclusion Criteria:

* age \< 18 years
* Karnofsky-index \< 60
* treatment with fludarabine or mitoxantrone within the preceding three months
* active auto-immune hemolytic anemia at the start of FCM chemotherapy
* participation in another clinical trial during the last 4 weeks
* participation in this study before
* previous treatment with murine antibodies
* concurrent diseases which exclude the administration of therapy as outlined by the study protocol
* non-compensated heart failure
* dilatative cardiomyopathy
* coronary heart disease with ST segment depression in ECG
* myocardial infarction during the last 6 months
* chronic lung disease with hypoxemia
* severe non-compensated hypertension
* severe non-compensated diabetes mellitus
* renal insufficiency (creatinine \> 2.0 mg/dl), not related to lymphoma
* hepatic insufficiency with transaminase values greater than 3-fold of normal values and/or bilirubin levels \> 2.0 mg/dl, not related to lymphoma
* clinical signs of cerebral dysfunction
* women during lactation or pregnancy or of childbearing potential not using a reliable contraceptive method
* severe psychiatric disease
* serological positivity for HBV, HCV, HIV
* previous organ transplantation other than autologous peripheral blood stem cell transplantation
* missing written informed consent or missing written consent for data protection

Primary outcomes:
measure: Remission rate
measure: Event free interval
Secondary outcomes:
measure: Time to Progression
measure: Overall survival
measure: adverse events
measure: serious infectious complications
Other outcomes:
Locations:
city: Munich
country: Germany
facility: German Low Grade Study Group (Glsg)
Study officials:
affiliation: University Hospital Großhadern/LMU, Dept. of Medicine III
name: Hiddemann Wolfgang, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Forstpointner R, Dreyling M, Repp R, Hermann S, Hanel A, Metzner B, Pott C, Hartmann F, Rothmann F, Rohrberg R, Bock HP, Wandt H, Unterhalt M, Hiddemann W; German Low-Grade Lymphoma Study Group. The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2004 Nov 15;104(10):3064-71. doi: 10.1182/blood-2004-04-1323. Epub 2004 Jul 29.
citation: Forstpointner R, Unterhalt M, Dreyling M, Bock HP, Repp R, Wandt H, Pott C, Seymour JF, Metzner B, Hanel A, Lehmann T, Hartmann F, Einsele H, Hiddemann W; German Low Grade Lymphoma Study Group (GLSG). Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: Results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG). Blood. 2006 Dec 15;108(13):4003-8. doi: 10.1182/blood-2006-04-016725. Epub 2006 Aug 31.