Clinical trial NCT00491491: Zevalin-beam for Aggressive Lymphoma
Official title: SPINOZA / שפינוזה. Study With Preparatory INduction Of Zevalin in Aggressive Lymphoma. A Randomized Phase 3 Study of BEAM Versus 90Yttrium Ibritumomab Tiuxetan (Zevalin) / BEAM in Patients Requiring Autologous Hematopoietic Stem Cell Transplantation (ASCT) for Relapsed Diffuse Large B-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-Hodgkin's Lymphoma
Keywords: non-Hodgkin's lymphoma
autologous stem cell transplantation
radioimmunotherapy
zevalin
Lead sponsor: Sheba Medical Center
Sponsor class: OTHER_GOV
Collaborators: name: City of Hope Medical Center
name: Amsterdam UMC, location VUmc
name: University of Göttingen
First posted: 2007-06-26
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study hypothesis is that the addition of zevalin radioimmunotherapy to the conditioning regimen given prior to BEAM high-dose chemotherapy and autologous stem cell transplantation in patients with aggressive lymphoma will reduced disease recurrence rate and improve overall and disease-free survival.


Eligibility criteria: Inclusion Criteria:

1. Patients with CD20 positive diffuse large B-cell lymphoma as confirmed by a pathological biopsy report.
2. Patients who are candidates for autologous stem-cell transplantation due to primary refractory or first relapse of disease.
3. Patients must have chemo-sensitive disease achieving at least partial response (Cheson 2007 criteria) to last chemotherapy.
4. Age ≥ 18 years and age ≤ 70
5. Patients with adequate autologous stem cell collection for transplantation (target ≥ 2.5 x 106 CD34+ cells/kg).
6. Patients must sign written informed consent.
7. Adequate birth control in fertile patients.
8. All prior chemotherapy completed at least three weeks before study treatment.
9. Marrow involvement less than 25% at transplantation, no limitation on blood counts (low platelet count allowed).
10. Negative HIV antibody.

Exclusion Criteria:

1. 1. Chemo-refractory disease as determined by less than partial response (Cheson 2007 Criteria) to last chemotherapy.
2. Two or more relapses after initial response to induction chemotherapy.
3. High-grade transformation from earlier diagnosis of low-grade lymphoma. Patients with "De Novo" Transformed DLBCL, defined as DLBCL only on lymph node biopsy and a discordant marrow with para-trabecular small cells at first diagnosis of lymphoma, are eligible if adherent all other selection criteria.
4. Bilirubin \> 3.0 mg/dl, transaminases \> 3 times upper normal limit.
5. Creatinine \> 2.0 mg/dl.
6. ECOG Performance status \> 2.
7. Uncontrolled infection.
8. Pregnancy or lactation.
9. Abnormal lung diffusion capacity (DLCO \< 40% predicted).
10. Severe cardiovascular disease; New York Heart Association (NYHA) Functional Classification ≥2.
11. Active CNS disease involvement.
12. Presence of any other malignancy or history of prior malignancy within 5 years of study entry. Within 5 years, patients treated for Stage I or II cancers are eligible provided they have a life expectancy \> 5 years in relation to this prior malignance. The 5-year exclusion rule does not apply to-non melanoma skin tumors and in situ cervical cancer.
13. Pleural effusion or ascites \> 1 liter.
14. Known hypersensitivity to rituximab.
15. Psychiatric conditions/disease that impair the ability to give informed consent or to adequately co-operate.
16. Prior radioimmunotherapy.
17. Prior autologous or allogeneic HSCT.
18. Active evidence of Hepatitis B or C infection; Hepatitis B surface antigen positive.
19. Patients who have had prior radiation to the lung will be excluded from the study, although mediastinal irradiation will be permitted if minimal lung is in the treatment volume.
20. Patients who have received \>500cGy radiation to the kidneys will be excluded from the study.

Primary outcomes:
measure: Overall Survival
timeFrame: 2 years after transplantation
Secondary outcomes:
measure: Progression-free Survival
timeFrame: 2 years after transplantation
measure: Clinical Response
timeFrame: 100 days after transplantation
measure: Hematopoietic Recovery
timeFrame: 100 days after transplantation
measure: Grade III Toxicity
timeFrame: 100 days after transplantation
measure: Secondary Malignancies
timeFrame: 5 years after transplantation
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Göttingen
country: Germany
facility: Georg-August Universität
city: Tel Hashomer
country: Israel
facility: Chaim Sheba Medical Center
city: Amsterdam
country: Netherlands
facility: VU Medical Center
Study officials:
affiliation: Chaim Sheba Medical Center, Tel Hashomer, Israel
name: Avichai Shimoni, MD
role: STUDY_CHAIR
affiliation: City of Hope National Medical Center, Duarte, CA
name: Amrita Krishnan, MD
role: STUDY_CHAIR
References: