Safety of Ibritumomab Tiuxetan (Zevalin®) in Combination With a Fludarabine-based Reduced Intensity Conditioning (RIC) Regimen (ZEVALLO 2007) (ZEVALLO)

October 4, 2016 updated by: University Hospital, Bordeaux

Safety and Efficacy of Ibritumomab Tiuxetan (Zevalin®) in Association With a Fludarabine Based Reduced Conditioning Regimen and Allogenic Stem Cell Support in Chemo-sensitive Relapsed CD20 Positive Aggressive Non-Hodgkin's Lymphoma Patients.

The purpose of this study is to evaluate the safety and efficacy of Zevalin® in a Reduced Intensity Conditioning regimen followed by allogenic stem cell support in patients with aggressive lymphomas who are responsive to a salvage chemotherapy regimen.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The benefit of Zevalin® in the setting of autologous stem cell transplantation has been largely reported. The addition of Zevalin® to a fludarabine-based Reduced Intensity Conditioning regimen has been already evaluated in the setting of allo-SCT and the results reported so far seem to be promising without an overwhelming toxicity neither a delayed hematologic recovery. The assumption that the addition of Zevalin® to the conditioning regimen might improve lymphoma control and the demonstration that nucleoside analogs such as fludarabine synergize optimally with RIT led us to conduct this trial using the following preparative regimen: rituximab 250 mg/m² on days -21 and -14, Zevalin® 0,4 mCi/Kg body weight on day -14, fludarabine 30 mg/m² intravenously from days -6 to -2, Busulfan orally (4 mg/Kg body weight) or intravenously (0,8 mg/Kg body weight) on days -5 and -4 and ATG (Thymoglobulin®) 2,5 mg/Kg body weight intravenously on day -1. Cyclosporine A is administered at 2 or 3 mg/Kg body weight from day -1 to day 28 than followed by a dose reduction.

The purpose of this study is to evaluate the safety and efficacy of Zevalin® in a Reduced Intensity Conditioning regimen followed by allogenic stem cell support in patients with aggressive lymphomas who are responsive to a salvage chemotherapy regimen

Patients are followed from the beginning of the RIC regimen until day 365 for primary and secondary objectives of the study than on a regular basis depending on the practice of each centre. The evaluation includes physical examination (performance status, hematologic assessment, acute and chronic GVH disease), biologic tests (blood screening for blood count, renal and hepatic function, B and T-cell recovery, chimerism analysis, response assessment) and complementary examinations (marrow biopsies, tomography scan, positron emission tomography, …).

Study Type

Interventional

Enrollment (Actual)

31

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

  • France
      • Besançon, France, 25030
        • Service d'hématologie - CHU de Besançon
      • Bordeaux - Pessac, France, 33600
        • Service des maladies du sang - Hôpital Haut-Lévêque - avenue de magellan
      • Clermont-Ferrand, France, 63000
        • Service d'hématologie - CHU Hôtel Dieu Clermont-Ferrand
      • Clermont-Ferrand, France, 63011
        • Service de médecine nucléaire - Centre de Lutte contre le Cancer de la Région Auvergne Jean Perrin
      • Lyon, France, 69437
        • Hôpital Edouard Herriot
      • Marseille, France, 13009
        • Service d'Oncologie Hématologie, Institut Paoli Calmettes - 232 Bd Ste Marguerite
      • Montpellier, France, 34295
        • Hématologie et Oncologie médicale - CHU Lapeyronie
      • Nantes, France, 44093
        • Service d'Hématologie, Hôpital Hôtel Dieu, CHU Nantes - 1 Place Alexis Ricordeau
      • Nice, France, 06202
        • Service d'hématologie clinique - Hôpital l'Archet 1
      • Paris, France, 75015
        • Service d'Hématologie Adultes - Hôpital Necker-Enfants Malade
      • Paris, France, 75475
        • Pôle hématologie et immunologie clinique - Hôpital Saint-Louis
      • Strasbourg, France, 67098
        • Département d'hématologie et d'Oncologie - CHRU Hautepierre

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:

  • Age ≥ 18 and ≤ 65

  • Patients with this lymphoma:

    1. CD20 positive diffuse large B-cell lymphoma in relapse or refractory after two prior regimens or after one regimen including autologous stem cell transplantation, or
    2. CD20 positive mantle-cell lymphoma in relapse or refractory after two prior regimens or after one regimen including autologous stem cell transplantation or
    3. Other CD20 positive aggressive lymphoma for which an indication of allograft is selected (Burkitt lymphoma, lymphoblastic lymphoma, intra-vascular lymphoma…..) or
    4. Low grade lymphoma CD20 positive (follicular lymphoma, marginal zone lymphoma) in histological processing or
    5. Low grade lymphoma CD20 positive for which an indication of allograft is selected
  • And sensitive to relapse's treatment
  • HLA-matched related or unrelated donor 10/10 or 9/10 with C or DQ mismatch without contra-indication for stem cell mobilization
  • ECOG (Eastern Cooperative Oncology Group) < 2
  • Having or not received previously rituximab
  • With a chemosensitive relapse NHL (at least partial response > 50% as defined with cheson criteria (See appendix 5)
  • Eligible for an allogenic transplant
  • With a signed informed consent (obtained on the screening day at the latest and before any investigation)
  • Patient affiliated to or beneficiary of the National Health Service

Exclusion Criteria:

  • Patient allografted previously
  • History of cancer
  • Patient with HIV or HCV positive serology and requiring treatment
  • Childbearing or child breastfeeding women
  • Women who are pregnant or nursing, or man, in the absence of effective contraception during treatment and up to 12 months after stopping treatment
  • Any contraindication to allogenic stem cell transplantation:
  • Cardiac insufficiency (ejection fraction < 50% by echocardiography)
  • Respiratory insufficiency defined as DLCO below 50% of the theoretical value
  • Renal failure defined as creatinin clearance < 30 ml/mn
  • Hepatic failure defined as a 2-fold increase of bilirubin or transaminases except if due to the lymphoma
  • Known hypersensitivity to murine antibodies and other proteins, the active ingredients or any of the ingredients of the products under review
  • Patient under the protection of justice

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Zevalin
Zevalin associated with a Fludarabine-based reduced-intensity conditioning regimen,all patients will receive Zevalin in the conditioning regimen
Drug: Ibritumomab Tiuxetan (Zevalin)

Conditioning regimen followed by allogeneic hematopoietic stem cell transplantation.

Ibritumomab Tiuxetan(Zevalin): 0.4 mCi/kg IV at day -14 (Day 0 is the transplantation)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
the treatment-related mortality rate (except if the death is related to the lymphoma exclusively).
Time Frame: day 100 post transplant
day 100 post transplant

Secondary Outcome Measures

Outcome Measure
Time Frame
The event-free-survival (EFS)(an event is defined as: death from any cause, relapse or progression, need to another treatment except for donor-lymphocytes injection (DLI), patient lost for follow-up)
Time Frame: 1 year post transplant
1 year post transplant
The rate of hematologic recovery (defined as ANC above 500/mm3 and platelets count above 20.000/mm3 for three consecutive days without stimulating growth support neither platelet transfusion)
Time Frame: day 30
day 30
Biological post allogenic effects of Zevalin® on the incidence of GVHD and B-cell and T-cell reconstitution
Time Frame: days d0, d28, d90, d180 and 1 year
days d0, d28, d90, d180 and 1 year
Chimérism
Time Frame: day d28, d56, d 80, 1 year than at least once a year
day d28, d56, d 80, 1 year than at least once a year

Collaborators and Investigators

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

Sponsor

University Hospital, Bordeaux

Collaborators

Bayer

Investigators

  • Principal Investigator: Krimo BOUABDALLAH, MD, University Hospital Bordeaux, France
  • Study Chair: Geneviève CHENE, Pr, University Hospital Bordeaux, France

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

February 1, 2008

Primary Completion (Actual)

February 1, 2011

Study Completion (Actual)

November 1, 2011

Study Registration Dates

First Submitted

January 23, 2008

First Submitted That Met QC Criteria

February 5, 2008

First Posted (Estimate)

February 6, 2008

Study Record Updates

Last Update Posted (Estimate)

October 5, 2016

Last Update Submitted That Met QC Criteria

October 4, 2016

Last Verified

February 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHUBX 2007/11

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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