Overview

This trial is active, not recruiting.

Conditions lymphoma, follicular, lymphoma, low-grade, lymphoma, intermediate-grade
Treatments fcm, r-fcm, rituximab maintenance, observation only
Phase phase 3
Target CD20
Sponsor Ludwig-Maximilians - University of Munich
Start date November 1998
End date June 2001
Trial size 319 participants
Trial identifier NCT00317096, NHL-1998-1

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model factorial assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
All patients underwent a central randomization procedure. Randomization was done by a Computer program stratified for histology, Response to the preceding chemotherapy, and the number of previous chemotherapies using the method of permutuated blocks. The FCM combination comprised: 25 mg/m2 fludarabine per day iv over 30 minutes, days 1 to 3 200 mg/m2 cyclophosphamide per day as a 4-hour-infusion, days 1 to 3 8 mg/m2 mitoxantrone per day iv over 30 minutes, day 1 4 treatment Cycles á 4 weeks per cycle In patients with peripheral lymphocyte Counts more than 20.000/mm3 and/or a large Tumor mass (ie, bulky disease more than 10 cm) a cytoreductive pre-phase could be performed, comprising cyclophosphamide at a dose of 200 mg/m2 as a 1-hour-infusion over 3 to 5 days.
fcm
Active comparator: Chemotherapy
(Experimental)
All patients underwent a central randomization procedure. Randomization was done by a Computer program stratified for histology, Response to the preceding chemotherapy, and the number of previous chemotherapies using the method of permutuated blocks. The R-FCM combination comprised: 375 mg/m2 rituximab on the day before the respective FCM course. 25 mg/m2 fludarabine per day iv over 30 minutes, days 1 to 3 200 mg/m2 cyclophosphamide per day as a 4-hour-infusion, days 1 to 3 8 mg/m2 mitoxantrone per day iv over 30 minutes, day 1 4 treatment Cycles á 4 weeks per cycle In patients with peripheral lymphocyte Counts more than 20.000/mm3 and/or a large Tumor mass (ie, bulky disease more than 10 cm) a cytoreductive pre-phase could be performed, comprising cyclophosphamide at a dose of 200 mg/m2 as a 1-hour-infusion over 3 to 5 days.
r-fcm
experimental: Chemotherapy with additional rituximab
(Other)
Patients achieving a complete or partial remission after FCM or R-FCM underwent a subsequent randomization for 2 courses of rituximab to be given 3 and 6 months after completion of salvage therapy versus observation only. This second randomization was stratified for the type of salvage therapy with FCM or R-FCM, the Response to this Treatment (CR or PR), and histology.
observation only
no Intervention after completion of FCM or R-FCM
(Other)
Patients achieving a complete or partial remission after FCM or R-FCM underwent a subsequent randomization for 2 courses of rituximab to be given 3 and 6 months after completion of salvage therapy versus observation only. Courses of rituximab consisted of 4 doses of 375 mg/m2 per day given at 4 consecutive weeks. This second randomization was stratified for the type of salvage therapy with FCM or R-FCM, the Response to this Treatment (CR or PR), and histology.
rituximab maintenance
2 courses of rituximab maintenance after completion of salvage therapy

Primary Outcomes

Measure
Remission rate
time frame:
Event free interval
time frame:

Secondary Outcomes

Measure
Time to Progression
time frame:
Overall survival
time frame:
adverse events
time frame:
serious infectious complications
time frame:

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

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
Principal investigator Hiddemann Wolfgang, PhD
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.
Trial information was received from ClinicalTrials.gov and was last updated in September 2015.
Information provided to ClinicalTrials.gov by Ludwig-Maximilians - University of Munich.