The objective of this study is to evaluate the efficacy and the safety of Zevalin-BEAM preparative regimen before ASCT as measured by the event free survival.

The goal is to obtain 15% increase of EFS at 2 years.

Condition	Intervention	Phase
B Cell Lymphoma	Drug: Zevalin plus BEAM	Phase II

Further Study Details: 

Primary Outcomes: EFS(Event free survival)
Secondary Outcomes: Overall response rate (ORR); Toxicities,transplant related mortality at 1 and 2 years; Hematological reconstitution after ASCT and 1 year; Time to progression or relapse, disease free survival for complete responders after ASCT, overall survival.
Expected Total Enrollment:  75

The indolent course of the low-grade B-cell lymphoma is thus characterized by multiple remissions and relapses with ever-shortening “time to progression” intervals, and by ultimately becoming refractory to treatment. In this situation of recurrences, intensive therapy including high-dose chemotherapy or chemo-radiotherapy followed by autologous hematopoietic stem cell transplantation appears as a therapeutic option. With the use of peripheral blood stem cell, the autologous stem cell transplantation (ASCT) procedure has become easier and cheaper, and it has a mortality rate of below 5% and manageable morbidity. EBMT registry data or institution driven studies have shown an improvement in event free survival when compared to chemotherapy in relapsing patients. Recently Schouten et al reported in a randomized study a significant benefit in survival for patients submitted in relapse to ASCT . Consolidation with ASCT has been studied in first line treatment and showed a significant improvement in survival in one randomized study. BEAM regimen is a referent high-dose chemotherapy used in intensive therapy followed by ASCT in the treatment of malignant lymphoma . It could therefore be considered for patients with indolent lymphoma if it could be shown to improve survival. In most studies the conditioning regimen was associating chemotherapy and Total Body Irradiation (TBI) for indolent lymphoma as it is very sensitive to even low dose of radiotherapy. TBI however is time consuming and technically not available in all transplant centers and associated with some long term toxicities; a search for more specific targeted irradiation has been a goal for several years.

Recently, a new preparative regimen for older patients with aggressive CD20-positive B-cell lymphoma utilizing standard-dose 0.4 mCi/kg 90Y ibritumomab tiuxetan combined with high-dose BEAM followed by ASCT showed a CR rate of 92% with a follow-up of 9 months. Finally, high-dose radioimmunotherapy with 90Y ibritumomab tiuxetan and high-dose cyclophosphamide/etoposide followed by ASCT for poor-risk or relapsed B-cell NHL have been reported, with a 2-year DFS of 80%. The use of conventional dose of Yttrium did not need heavy radioprotection procedures, and can be widely distributes in transplant centers.

Overall toxicities were comparable to standard autologous transplantation conditioning regimens, and the combined treatment was well tolerated. The hematological reconstitution after transplantation occurred without delay, except in two cases than in control-based high-dose chemotherapy alone population. Mucositis and neutropenic fever were reported without increase of severity. Nonhematological adverse events have been observed, three interstitial pneumonitis , mild abnormalities on liver or kidney function tests, except one case of veno-occlusive disease, and 4 fatal infection (disseminated aspergillosis with a brain abscess, streptococcal sepsis, staphylococcal sepsis, and disseminated varicella zoster).

Therefore, all these data support a phase II trial evaluating efficacy and toxicities in patients with low grade B-Cell lymphoma of a new preparative regimen combining at standard dose 90Y ibritumomab tiuxetan and high-dose BEAM chemotherapy followed by ASCT.

Ages Eligible for Study:  18 Years   -   65 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Aged from 18 to 65 years,
• Patient with pathologically proven at relapse, low grade B-Cell lymphoma CD20 positive (WHO classification):

Marginal zone, or Lymphocytic, or Follicular,

• In relapse after CR, less than PR or partial response ( maximum 3 lines of treatment),
• Previously treated with chemotherapy regimen with or without rituximab,
• With a chemo-sensitive disease using salvage therapy,
• Eligible for autologous stem cell transplantation,
• ECOG performance status 0 to 2,
• With a minimum life expectancy of 3 months,
• Negative HIV, HBV and HCV serologies < 4 weeks (except after vaccination),
• Signed informed consent form.

Exclusion Criteria:

• Histological transformation in diffuse large cell from a low grade B-Cell lymphoma,
• Prior transplantation,
• Contraindication to any drug contained in the chemotherapy regimens,
• Large bone marrow irradiation > 40%,
• Bone marrow infiltration > 25%
• Lack of sufficient autologous stem cells for transplantation,
• Treatment with any investigational drug within 30 days before planned first cycle of chemotherapy and during the study,
• Any serious active disease or co-morbid medical condition (according to the investigator’s decision and information provided in the IDB),
• Poor bone marrow reserve as defined by neutrophils < 1.5 G/l or platelets < 100 G/l, unless related to bone marrow infiltration,
• Poor renal function (creatinin level > 2.5 maximum normal level) unless these abnormalities are related to the lymphoma,
• Poor hepatic function (total bilirubin level > 30 mmol/l, transaminases > 2.5 maximum normal level) unless these abnormalities are related to the lymphoma,
• Any history of cancer during the last 5 years, with the exception of non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma,
• Presence of anti-murine antibody (HAMA) reactivity,
• Known hypersensitivity to murine antibodies or proteins,
• Pregnant woman,
• Adult patient unable to give informed consent because of intellectual impairment.

Please refer to this study by ClinicalTrials.gov identifier  NCT00138086

Christian Gisselbrecht, MD PHD      +33142499811    christian.gisselbrecht@sls.ap-hop-paris.fr
Guylène Chartier      +33142499811    guylene.chartier@chu-stlouis.fr

Belgium
      Groupe d''''Etude des Lymphomes de l''''adulte, Mont-Godinne,  Belgium; Not yet recruiting
France
      Centre Henri Becquerel, Rouen,  76038,  France; Recruiting
      Hôpital Henri Mondor, Créteil,  94010,  France; Recruiting
      Hôpital Saint Louis, Paris,  75010,  France; Recruiting
      Service d''''Hématologie - Centre Hospitalier Lyon-Sud, Pierre-Bénite cedex,  69495,  France; Recruiting
      Institut Curie, Paris,  75005,  France; Recruiting
      Hématologie CHU de Lille, Lille,  59000,  France; Recruiting
      Institut Gustave Roussy, Villejuif,  France; Recruiting
Switzerland
      Schweirische Arbeitsgruppe fur klinische Krebsforschung, Lausanne,  Switzerland; Not yet recruiting

Study chairs or principal investigators

Christian Gisselbrecht, MD PHD,  Principal Investigator,  Groupe d''''Etudes de Lymphomes de L''''Adulte   

Study ID Numbers:  Z-BEAM
Last Updated:  August 29, 2005
Record first received:  August 29, 2005
ClinicalTrials.gov Identifier:  NCT00138086
Health Authority: France: Afssaps - French Health Products Safety Agency
ClinicalTrials.gov processed this record on 2005-08-30