Zevalin-beam for Aggressive Lymphoma

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

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.

Study Overview

• Status: Completed
• Conditions: Non-Hodgkin's Lymphoma
• Intervention / Treatment: Drug: ibritumomab tiuxetan; Procedure: BEAM chemotherapy and autologous stem-cell transplantation

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Göttingen, Germany
    • Georg-August Universität
• Israel
  • Tel Hashomer, Israel
    • Chaim Sheba Medical Center
• Netherlands
  • Amsterdam, Netherlands
    • VU Medical Center
• United States
  • Arizona
    • Scottsdale, Arizona, United States
      • Mayo Clinic Arizona
  • California
    • Duarte, California, United States, 91010-3000
      • City of Hope National Medical Center
    • Los Angeles, California, United States
      • Cedars Sinai Medical Center
  • Florida
    • Tampa, Florida, United States
      • Moffitt Cancer Center
  • Illinois
    • Chicago, Illinois, United States
      • Northwestern University
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Z-BEAM; ibritumomab tiuxetan (zevalin) BEAM	Drug: ibritumomab tiuxetan; 0.4 mCi/kg; Other Names: zevalin; Procedure: BEAM chemotherapy and autologous stem-cell transplantation
Active Comparator: standard BEAM; standard BEAM chemotherapy	Procedure: BEAM chemotherapy and autologous stem-cell transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	actuarial 2 year survival	2 years after transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	actuarial 2-year PFS	2 years after transplantation
Clinical Response	complete response (CR) and partial response (PR) proportion at day 100,	100 days after transplantation
Hematopoietic Recovery	time to hematopoietic recovery	100 days after transplantation
Grade III Toxicity	incidence of infection, grade III-IV toxicities, treatment-related mortality	100 days after transplantation
Secondary Malignancies	incidence of myelodysplastic syndrome (MDS), and secondary acute myelogenous leukemia (AML).	5 years after transplantation

Collaborators and Investigators

• Sponsor: Sheba Medical Center
• Collaborators: City of Hope Medical Center; Amsterdam UMC, location VUmc; University of Göttingen
• Investigators: Study Chair: Avichai Shimoni, MD, Chaim Sheba Medical Center, Tel Hashomer, Israel; Study Chair: Amrita Krishnan, MD, City of Hope National Medical Center, Duarte, CA

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: June 25, 2007
• First Submitted That Met QC Criteria: June 25, 2007
• First Posted (Estimate): June 26, 2007

Study Record Updates

• Last Update Posted (Actual): August 31, 2020
• Last Update Submitted That Met QC Criteria: August 13, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: autologous stem cell transplantation; non-Hodgkin's lymphoma; radioimmunotherapy; zevalin
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: SHEBA-07-4466-AN-CTIL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No