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

Mantle Cell Lymphoma Clinical Trial

— ZEVALLO  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00607854
• Other study ID #: CHUBX 2007/11
• Status: Completed
• Phase: Phase 2
• First received: January 23, 2008
• Last updated: October 4, 2016
• Start date: February 2008
• Est. completion date: November 2011

Study information

• Verified date: February 2013
• Source: University Hospital, Bordeaux
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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, …).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: November 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Diffuse Large B-Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Mantle-Cell
• Mantle Cell Lymphoma

Intervention

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)

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Bordeaux	Bayer

Country where clinical trial is conducted

France, 

References & Publications (29)

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* Note: There are 29 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the treatment-related mortality rate (except if the death is related to the lymphoma exclusively).		day 100 post transplant	Yes
Secondary	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)		1 year post transplant	Yes
Secondary	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)		day 30	Yes
Secondary	Biological post allogenic effects of Zevalin® on the incidence of GVHD and B-cell and T-cell reconstitution		days d0, d28, d90, d180 and 1 year	Yes
Secondary	Chimérism		day d28, d56, d 80, 1 year than at least once a year	Yes