NCT00317096

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
319

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Nov 1998

Longer than P75 for phase_3

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 1998

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2001

Completed
4.9 years until next milestone

First Submitted

Initial submission to the registry

April 20, 2006

Completed
4 days until next milestone

First Posted

Study publicly available on registry

April 24, 2006

Completed
15.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2021

Completed
Last Updated

May 7, 2021

Status Verified

May 1, 2021

Enrollment Period

2.6 years

First QC Date

April 20, 2006

Last Update Submit

May 6, 2021

Conditions

Lymphoma, FollicularLymphoma, Low-GradeLymphoma, Intermediate-Grade

Keywords

Drug TherapyMaintenancerituximab

Outcome Measures

Primary Outcomes (2)

  • Remission rate

  • Event free interval

Secondary Outcomes (4)

  • Time to Progression

  • Overall survival

  • adverse events

  • serious infectious complications

Study Arms (4)

FCM

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.

Procedure: FCM

R-FCM

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.

Procedure: R-FCM

Observation only

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.

Other: observation only

rituximab maintenance

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.

Drug: rituximab maintenance

Interventions

FCMPROCEDURE

Active comparator: Chemotherapy

FCM
R-FCMPROCEDURE

experimental: Chemotherapy with additional rituximab

R-FCM
rituximab maintenanceDRUG

2 courses of rituximab maintenance after completion of salvage therapy

rituximab maintenance
observation onlyOTHER

no Intervention after completion of FCM or R-FCM

Observation only

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • +8 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

German Low Grade Study Group (Glsg)

Munich, D-81377, Germany

Location

Related Publications (2)

  • 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.

    PMID: 15284112RESULT

  • 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.

    PMID: 16946304RESULT

MeSH Terms

Conditions

Lymphoma, FollicularLymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

LymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Study Officials

  • Hiddemann Wolfgang, PhD

    University Hospital Großhadern/LMU, Dept. of Medicine III

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
FACTORIAL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Prof. Dr. Wolfgang Hiddemann

Study Record Dates

First Submitted

April 20, 2006

First Posted

April 24, 2006

Study Start

November 1, 1998

Primary Completion

June 1, 2001

Study Completion

June 1, 2021

Last Updated

May 7, 2021

Record last verified: 2021-05

Locations

DE(1)