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

May 6, 2021 updated by: Prof. Dr. Wolfgang Hiddemann, Ludwig-Maximilians - University of Munich

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

319

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Munich, Germany, D-81377
        • German Low Grade Study Group (Glsg)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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.
Procedure: FCM
Active comparator: Chemotherapy
Experimental: 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.
Procedure: R-FCM
experimental: Chemotherapy with additional rituximab
Other: 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.
Other: observation only
no Intervention after completion of FCM or R-FCM
Other: 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.
Drug: rituximab maintenance
2 courses of rituximab maintenance after completion of salvage therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Remission rate
Event free interval

Secondary Outcome Measures

Outcome Measure
adverse events
Overall survival
serious infectious complications
Time to Progression

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ludwig-Maximilians - University of Munich

Investigators

  • Principal Investigator: Hiddemann Wolfgang, PhD, University Hospital Großhadern/LMU, Dept. of Medicine III

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 1998

Primary Completion (Actual)

June 1, 2001

Study Completion (Anticipated)

June 1, 2021

Study Registration Dates

First Submitted

April 20, 2006

First Submitted That Met QC Criteria

April 21, 2006

First Posted (Estimate)

April 24, 2006

Study Record Updates

Last Update Posted (Actual)

May 7, 2021

Last Update Submitted That Met QC Criteria

May 6, 2021

Last Verified

May 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NHL-1998-1

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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