FCM Versus R-FCM Followed by R-Maintenance or Observation Only

NCT ID: NCT00317096

Last Updated: 2021-05-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

319 participants

Study Classification

INTERVENTIONAL

Study Start Date

1998-11-30

Study Completion Date

2021-06-30

Brief Summary

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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

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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.

Conditions

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Lymphoma, Follicular Lymphoma, Low-Grade Lymphoma, Intermediate-Grade

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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FCM

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.

Group Type ACTIVE_COMPARATOR

FCM

Intervention Type PROCEDURE

Active comparator: Chemotherapy

R-FCM

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.

Group Type EXPERIMENTAL

R-FCM

Intervention Type PROCEDURE

experimental: Chemotherapy with additional rituximab

Observation only

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.

Group Type OTHER

observation only

Intervention Type OTHER

no Intervention after completion of FCM or R-FCM

rituximab maintenance

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.

Group Type OTHER

rituximab maintenance

Intervention Type DRUG

2 courses of rituximab maintenance after completion of salvage therapy

Interventions

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FCM

Active comparator: Chemotherapy

Intervention Type PROCEDURE

R-FCM

experimental: Chemotherapy with additional rituximab

Intervention Type PROCEDURE

rituximab maintenance

2 courses of rituximab maintenance after completion of salvage therapy

Intervention Type DRUG

observation only

no Intervention after completion of FCM or R-FCM

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ludwig-Maximilians - University of Munich

OTHER

Sponsor Role lead

Responsible Party

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Prof. Dr. Wolfgang Hiddemann

Prof. Dr. Wolfgang Hiddemann

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Hiddemann Wolfgang, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital Großhadern/LMU, Dept. of Medicine III

Locations

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German Low Grade Study Group (Glsg)

Munich, , Germany

Site Status

Countries

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Germany

References

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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.

Reference Type RESULT
PMID: 15284112 (View on PubMed)

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.

Reference Type RESULT
PMID: 16946304 (View on PubMed)

Other Identifiers

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NHL-1998-1

Identifier Type: -

Identifier Source: org_study_id

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