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

Information source: University Hospital, Bordeaux
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Diffuse Large B-Cell Lymphoma; Mantle Cell Lymphoma

Intervention: Ibritumomab Tiuxetan (Zevalin) (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: University Hospital, Bordeaux

Official(s) and/or principal investigator(s):
Krimo BOUABDALLAH, MD, Principal Investigator, Affiliation: University Hospital Bordeaux, France
Geneviève CHENE, Pr, Study Chair, Affiliation: University Hospital Bordeaux, France

Summary

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.

Clinical Details

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.

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: the treatment-related mortality rate (except if the death is related to the lymphoma exclusively).

Secondary outcome:

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)

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)

Biological post allogenic effects of Zevalin® on the incidence of GVHD and B-cell and T-cell reconstitution

Chimérism

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

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

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

Locations and Contacts

Service d'hématologie - CHU de Besançon, Besançon 25030, France

Service des maladies du sang - Hôpital Haut-Lévêque - avenue de magellan, Bordeaux - Pessac 33600, France

Service d'hématologie - CHU Hôtel Dieu Clermont-Ferrand, Clermont-Ferrand 63000, France

Service de médecine nucléaire - Centre de Lutte contre le Cancer de la Région Auvergne Jean Perrin, Clermont-Ferrand 63011, France

Hôpital Edouard Herriot, Lyon 69437, France

Service d'Oncologie Hématologie, Institut Paoli Calmettes - 232 Bd Ste Marguerite, Marseille 13009, France

Hématologie et Oncologie médicale - CHU Lapeyronie, Montpellier 34295, France

Service d'Hématologie, Hôpital Hôtel Dieu, CHU Nantes - 1 Place Alexis Ricordeau, Nantes 44093, France

Service d'hématologie clinique - Hôpital l'Archet 1, Nice 06202, France

Pôle hématologie et immunologie clinique - Hôpital Saint-Louis, Paris 75475, France

Service d'Hématologie Adultes - Hôpital Necker-Enfants Malade, Paris 75015, France

Département d'hématologie et d'Oncologie - CHRU Hautepierre, Strasbourg 67098, France

Additional Information

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Starting date: February 2008
Last updated: February 28, 2013

Page last updated: August 23, 2015

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