Monoclonal Antibody Therapy in Relapsed Non-Hodgkin's After Chemotherapy and Autologous Stem Cell Transplantation

Lymphoma Clinical Trial

Official title:

Phase I/II Study of IDEC-Y2B8 (Zevalin) for Post Transplant Relapses of B-Cell Non-Hodgkin's Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00031642
• Other study ID #: 0535-00-FB
• Secondary ID: CDR0000069211NCI
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 1, 2002
• Est. completion date: March 1, 2008

Study information

• Verified date: December 2023
• Source: University of Nebraska
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Monoclonal antibodies such as rituximab can locate cancer cells and deliver cancer-killing substances to them without harming normal cells. Radiolabeled monoclonal antibodies can locate and deliver radioactive cancer-killing substances.

PURPOSE: Phase I/II trial to study the effectiveness of combining radiolabeled monoclonal antibodies with rituximab in treating patients who have non-Hodgkin's lymphoma that has not responded to high-dose chemotherapy and autologous stem cell transplantation.

Description:

OBJECTIVES:

• Determine the maximum tolerated dose of yttrium Y 90-labeled ibritumomab tiuxetan when administered with rituximab in patients with B-cell non-Hodgkin's lymphoma who have relapsed after high-dose chemotherapy and autologous hematopoietic stem cell transplantation.

• Determine the safety and efficacy of this regimen in these patients.

OUTLINE: This is a dose-escalation study of yttrium Y 90-labeled ibritumomab tiuxetan (IDEC-Y2B8).

• Phase I: Patients receive rituximab IV over 4-6 hours followed by indium In 111-labeled ibritumomab tiuxetan (IDEC-In2B8) IV over 10 minutes on day 0. Patients receive rituximab IV again on day 7 followed by IDEC-Y2B8 IV over 10 minutes.

Cohorts of 3-6 patients receive escalating doses of IDEC-Y2B8 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 3 of 6 patients experience dose-limiting toxicity.

• Phase II: Once the MTD is determined, 58 additional patients are treated at that dose level as in phase I.

Patients are followed at 6 weeks, every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 78 patients (20 for phase I and 58 for phase II) will be accrued for this study within 2 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: March 1, 2008
• Est. primary completion date: November 1, 2005
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 120 Years

Eligibility

Inclusion Criteria:

• Diagnosis of relapsed B-cell non-Hodgkin's lymphoma (NHL) after high-dose chemotherapy and autologous stem cell transplantation

• Less than 25% bone marrow involvement with NHL as evidenced by unilateral or bilateral biopsy within the past 6 weeks

o Bone marrow biopsy should demonstrate 15-20% of cellular space occupied by normal hematopoiesis

• CD20 antigen expression in tumor tissue within the past year as evidenced by 1 of the following:

• Immunoperoxidase stains of tissue showing positive reactivity with L26 antibody

• Flow cytometry studies

• Measurable disease

o More than 2 cm bidimensionally

• 19 years of age and over

• Performance status WHO 0-2

• Life expectancy at least 3 months

• Absolute neutrophil count greater than 1,500/mm^3

• Platelet count greater than 150,000/mm^3

• Bilirubin less than 2.0 mg/dL

• SGOT or SGPT no greater than 2.5 times upper limit of normal (unless due to lymphomatous infiltration of the liver)

• Creatinine less than 2.0 mg/dL

• Fertile patients must use effective contraception during and for 6 months after study therapy

• HIV negative

• At least 4 weeks since prior growth factors

• At least 4 weeks since prior biologic therapy

• At least 4 weeks since any prior cytotoxic chemotherapy (6 weeks for nitrosoureas)

• At least 4 weeks since prior radiotherapy

• Recovered from all prior therapy

• At least 4 weeks since prior immunosuppressants

Exclusion Criteria:

• No active CNS lymphoma

• No HIV- or AIDS-related lymphoma

• No transfusion dependency

• No active obstructive hydronephrosis

• Not pregnant or nursing/negative pregnancy test

• No active infection requiring oral or IV antibiotics

• No human antimurine antibody positivity

• No other major medical problems

• No dependency on hematopoietic growth factors (e.g., epoetin alfa, interleukin-11, filgrastim [G-CSF], or sargramostim [GM-CSF])

• No prior radioimmunotherapy

• No other concurrent biologic therapy of any kind

• No prior fludarabine

• No concurrent chemotherapy

• No concurrent steroids except as maintenance for non-cancerous disease

• No prior pelvic radiotherapy

• No prior radiotherapy to more than 25% of estimated bone marrow reserve

• No concurrent external beam radiotherapy

• No other concurrent investigational drugs

• No other concurrent anti-cancer therapy

Related Conditions & MeSH terms

• Lymphoma

Intervention

Biological:
• rituximab

Radiation:
• yttrium Y 90 ibritumomab tiuxetan

Locations

Country	Name	City	State
United States	Eppley Cancer Center at University of Nebraska Medical Center	Omaha	Nebraska

Sponsors (2)

Lead Sponsor	Collaborator
University of Nebraska	Biogen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose
Primary	Safety and efficacy