Yttrium-90 Ibritumomab Tiuxetan (Zevalin) With BEAM in Relapsed Low Grade B-Cell Lymphoma

Lymphoma Study Association (LYSA)

Status and phase

Completed

Phase 2

Conditions

B-Cell Lymphoma

Treatments

Drug: Zevalin plus BEAM

Study type

Interventional

Funder types

Other

Identifiers

NCT00138086

Z-BEAM

Details and patient eligibility

About

The objective of this study is to evaluate the efficacy and the safety of Zevalin-BEAM preparative regimen before autologous stem cell transplantation (ASCT) as measured by the event free survival (EFS).

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

Full description

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 distributed 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 a standard dose 90Y ibritumomab tiuxetan and high-dose BEAM chemotherapy followed by ASCT.

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Aged 18 to 65 years
Patients with pathologically proven at relapse, low grade B-cell lymphoma CD20- positive (World Health Organization [WHO] classification):
- Marginal zone;
- Lymphocytic; or
- Follicular.
In relapse after complete remission (CR), less than partial remission (PR) or partial response (maximum of 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
Minimum life expectancy of 3 months
Negative HIV, hepatitis B virus (HBV) and hepatitis C virus (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 Investigational Drug Brochure [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 (creatinine level > 2.5 maximum normal level) unless abnormalities are related to the lymphoma
Poor hepatic function (total bilirubin level > 30 mmol/l, transaminases > 2.5 maximum normal level) unless 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 women
Adult patients unable to give informed consent because of intellectual impairment