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

This study has been completed.
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
University Hospital, Bordeaux
ClinicalTrials.gov Identifier:
NCT00607854
First received: January 23, 2008
Last updated: February 28, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Diffuse Large B-Cell Lymphoma
Mantle Cell Lymphoma
Drug: Ibritumomab Tiuxetan (Zevalin)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by University Hospital, Bordeaux:

Primary Outcome Measures:
  • the treatment-related mortality rate (except if the death is related to the lymphoma exclusively). [ Time Frame: day 100 post transplant ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Chimérism [ Time Frame: day d28, d56, d 80, 1 year than at least once a year ] [ Designated as safety issue: Yes ]

Enrollment: 31
Study Start Date: February 2008
Study Completion Date: November 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)


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, …).

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00607854

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

Publications:

Responsible Party: University Hospital, Bordeaux
ClinicalTrials.gov Identifier: NCT00607854     History of Changes
Other Study ID Numbers: CHUBX 2007/11
Study First Received: January 23, 2008
Last Updated: February 28, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Bordeaux:
Zevalin
Reduced intensity conditioning
Allogenic stem cell transplantation

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Fludarabine
Fludarabine phosphate
Antibodies, Monoclonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 19, 2014