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

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.

Sex

All

Minimum age

18 Years

Maximum age

65 Years

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

• BACKGROUNDCheson BD. The role of radioimmunotherapy with yttrium-90 ibritumomab tiuxetan in the treatment of non-Hodgkin lymphoma. BioDrugs. 2005;19(5):309-22. doi: 10.2165/00063030-200519050-00004. PMID 16207072
• BACKGROUNDChopra R, Goldstone AH, Pearce R, Philip T, Petersen F, Appelbaum F, De Vol E, Ernst P. Autologous versus allogeneic bone marrow transplantation for non-Hodgkin's lymphoma: a case-controlled analysis of the European Bone Marrow Transplant Group Registry data. J Clin Oncol. 1992 Nov;10(11):1690-5. doi: 10.1200/JCO.1992.10.11.1690. PMID 1403052
• BACKGROUNDDean RM, Fowler DH, Wilson WH, Odom J, Steinberg SM, Chow C, Kasten-Sportes C, Gress RE, Bishop MR. Efficacy of reduced-intensity allogeneic stem cell transplantation in chemotherapy-refractory non-hodgkin lymphoma. Biol Blood Marrow Transplant. 2005 Aug;11(8):593-9. doi: 10.1016/j.bbmt.2005.04.005. PMID 16041309
• BACKGROUNDEscalon MP, Champlin RE, Saliba RM, Acholonu SA, Hosing C, Fayad L, Giralt S, Ueno NT, Maadani F, Pro B, Donato M, McLaughlin P, Khouri IF. Nonmyeloablative allogeneic hematopoietic transplantation: a promising salvage therapy for patients with non-Hodgkin's lymphoma whose disease has failed a prior autologous transplantation. J Clin Oncol. 2004 Jun 15;22(12):2419-23. doi: 10.1200/JCO.2004.09.092. PMID 15197204
• BACKGROUNDFietz T, Uharek L, Gentilini C, Muessig A, Rieger K, Marinets O, Sandrock D, Munz DL, Glass B, Thiel E, Blau IW. Allogeneic hematopoietic cell transplantation following conditioning with 90Y-ibritumomab-tiuxetan. Leuk Lymphoma. 2006 Jan;47(1):59-63. doi: 10.1080/10428190500260478. PMID 16321828
• BACKGROUNDFrater JL, Hsi ED. Properties of the mantle cell and mantle cell lymphoma. Curr Opin Hematol. 2002 Jan;9(1):56-62. doi: 10.1097/00062752-200201000-00010. PMID 11753079
• Freytes CO, Loberiza FR, Rizzo JD, Bashey A, Bredeson CN, Cairo MS, Gale RP, Horowitz MM, Klumpp TR, Martino R, McCarthy PL, Molina A, Pavlovsky S, Pecora AL, Serna DS, Tsai T, Zhang MJ, Vose JM, Lazarus HM, van Besien K; Lymphoma Working Committee of the International Bone Marrow Transplant Registry. Myeloablative allogeneic hematopoietic stem cell transplantation in patients who experience relapse after autologous stem cell transplantation for lymphoma: a report of the International Bone Marrow Transplant Registry. Blood. 2004 Dec 1;104(12):3797-803. doi: 10.1182/blood-2004-01-0231. Epub 2004 Jul 27.