Yttrium-90 Ibritumomab Tiuxetan (Zevalin) With BEAM in Relapsed Low Grade B-Cell Lymphoma

September 6, 2006 updated by: Lymphoma Study Association

Targeted Intensification by a New Preparative Regimen for Patients With Low-Grade B-Cell Lymphoma Utilizing Standard-Dose Yttrium-90 Ibritumomab Tiuxetan (Zevalin) Radioimmunotherapy (RIT) Combined With High-Dose Beam Followed by Autologous Stem Cell Transplantation (ASCT)

The objective of this study is to evaluate the efficacy and the safety of Zevalin-BEAM preparative regimen before autologous stem cell transplantation (ASCT) as measured by the event free survival (EFS).

The goal is to obtain a 15% increase of EFS at 2 years.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The indolent course of the low-grade B-cell lymphoma is thus characterized by multiple remissions and relapses with ever-shortening "time to progression" intervals, and by ultimately becoming refractory to treatment. In this situation of recurrences, intensive therapy including high-dose chemotherapy or chemo-radiotherapy followed by autologous hematopoietic stem cell transplantation appears as a therapeutic option. With the use of peripheral blood stem cell, the autologous stem cell transplantation (ASCT) procedure has become easier and cheaper, and it has a mortality rate of below 5% and manageable morbidity. EBMT registry data or institution driven studies have shown an improvement in event free survival when compared to chemotherapy in relapsing patients. Recently Schouten et al reported in a randomized study a significant benefit in survival for patients submitted in relapse to ASCT. Consolidation with ASCT has been studied in first line treatment and showed a significant improvement in survival in one randomized study. BEAM regimen is a referent high-dose chemotherapy used in intensive therapy followed by ASCT in the treatment of malignant lymphoma. It could therefore be considered for patients with indolent lymphoma if it could be shown to improve survival. In most studies the conditioning regimen was associating chemotherapy and Total Body Irradiation (TBI) for indolent lymphoma as it is very sensitive to even low dose of radiotherapy. TBI however is time consuming and technically not available in all transplant centers and associated with some long term toxicities; a search for more specific targeted irradiation has been a goal for several years.

Recently, a new preparative regimen for older patients with aggressive CD20-positive B-cell lymphoma utilizing standard-dose 0.4 mCi/kg 90Y ibritumomab tiuxetan combined with high-dose BEAM followed by ASCT showed a CR rate of 92% with a follow-up of 9 months. Finally, high-dose radioimmunotherapy with 90Y ibritumomab tiuxetan and high-dose cyclophosphamide/etoposide followed by ASCT for poor-risk or relapsed B-cell NHL have been reported, with a 2-year DFS of 80%. The use of conventional dose of Yttrium did not need heavy radioprotection procedures, and can be widely distributed in transplant centers.

Overall toxicities were comparable to standard autologous transplantation conditioning regimens, and the combined treatment was well tolerated. The hematological reconstitution after transplantation occurred without delay, except in two cases than in control-based high-dose chemotherapy alone population. Mucositis and neutropenic fever were reported without increase of severity. Nonhematological adverse events have been observed, three interstitial pneumonitis, mild abnormalities on liver or kidney function tests, except one case of veno-occlusive disease, and 4 fatal infection (disseminated aspergillosis with a brain abscess, streptococcal sepsis, staphylococcal sepsis, and disseminated varicella zoster).

Therefore, all these data support a phase II trial evaluating efficacy and toxicities in patients with low grade B-Cell lymphoma of a new preparative regimen combining a standard dose 90Y ibritumomab tiuxetan and high-dose BEAM chemotherapy followed by ASCT.

Study Type

Interventional

Enrollment

75

Phase

  • Phase 2

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

  • Belgium
      • Mont-Godinne, Belgium
        • Groupe d'Etude des Lymphomes de l'Adulte
  • France
      • Créteil, France, 94010
        • Hôpital Henri Mondor
      • Lille, France, 59000
        • Hématologie CHU de Lille
      • Paris, France, 75010
        • Hopital Saint Louis
      • Paris, France, 75005
        • Institut Curie
      • Pierre-Bénite cedex, France, 69495
        • Service d'Hématologie - Centre Hospitalier Lyon-Sud
      • Rouen, France, 76038
        • Centre Henri Becquerel
      • Villejuif, France
        • Institut Gustave Roussy
  • Switzerland
      • Lausanne, Switzerland
        • Schweirische Arbeitsgruppe fur klinische Krebsforschung

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 to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Aged 18 to 65 years

  • Patients with pathologically proven at relapse, low grade B-cell lymphoma CD20- positive (World Health Organization [WHO] classification):

    • Marginal zone;
    • Lymphocytic; or
    • Follicular.
  • In relapse after complete remission (CR), less than partial remission (PR) or partial response (maximum of 3 lines of treatment)
  • Previously treated with chemotherapy regimen with or without rituximab
  • With a chemo-sensitive disease using salvage therapy
  • Eligible for autologous stem cell transplantation
  • ECOG performance status 0 to 2
  • Minimum life expectancy of 3 months
  • Negative HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) serologies < 4 weeks (except after vaccination)
  • Signed informed consent form

Exclusion Criteria:

  • Histological transformation in diffuse large cell from a low grade B-cell lymphoma
  • Prior transplantation
  • Contraindication to any drug contained in the chemotherapy regimens
  • Large bone marrow irradiation > 40%
  • Bone marrow infiltration > 25%
  • Lack of sufficient autologous stem cells for transplantation
  • Treatment with any investigational drug within 30 days before planned first cycle of chemotherapy and during the study
  • Any serious active disease or co-morbid medical condition (according to the investigator's decision and information provided in the Investigational Drug Brochure [IDB])
  • Poor bone marrow reserve as defined by neutrophils < 1.5 G/l or platelets < 100 G/l, unless related to bone marrow infiltration
  • Poor renal function (creatinine level > 2.5 maximum normal level) unless abnormalities are related to the lymphoma
  • Poor hepatic function (total bilirubin level > 30 mmol/l, transaminases > 2.5 maximum normal level) unless abnormalities are related to the lymphoma
  • Any history of cancer during the last 5 years, with the exception of non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma
  • Presence of anti-murine antibody (HAMA) reactivity
  • Known hypersensitivity to murine antibodies or proteins
  • Pregnant women
  • Adult patients unable to give informed consent because of intellectual impairment

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: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
EFS (event free survival)

Secondary Outcome Measures

Outcome Measure
Overall response rate (ORR)
Toxicities, transplant related mortality at 1 and 2 years
Hematological reconstitution after ASCT and 1 year
Time to progression or relapse, disease free survival for complete responders after ASCT, overall survival

Collaborators and Investigators

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

Sponsor

Lymphoma Study Association

Investigators

  • Principal Investigator: Christian Gisselbrecht, MD PHD, Lymphoma Study Association

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

March 1, 2005

Study Completion

March 1, 2009

Study Registration Dates

First Submitted

August 29, 2005

First Submitted That Met QC Criteria

August 29, 2005

First Posted (Estimate)

August 30, 2005

Study Record Updates

Last Update Posted (Estimate)

September 8, 2006

Last Update Submitted That Met QC Criteria

September 6, 2006

Last Verified

September 1, 2006

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Z-BEAM

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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