Monoclonal Antibody Therapy in Treating Patients With Non-Hodgkin's Lymphoma That Has Relapsed After High-Dose Chemotherapy and Autologous Stem Cell Transplantation

Sponsor

University of Nebraska (Other)

Overall Status

Completed

CT.gov ID

NCT00031642

Collaborator

Biogen (Industry)

Enrollment

Location

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: rituximab Radiation: yttrium Y 90 ibritumomab tiuxetan	Phase 1/Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

26 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jan 1, 2002

Actual Primary Completion Date :

Nov 1, 2005

Actual Study Completion Date :

Mar 1, 2008

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose []
Safety and efficacy []

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

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
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
More than 2 cm bidimensionally
No active CNS lymphoma
No HIV- or AIDS-related lymphoma

PATIENT CHARACTERISTICS:

Age:

19 and over

Performance status:

WHO 0-2

Life expectancy:

At least 3 months

Hematopoietic:

Absolute neutrophil count greater than 1,500/mm^3
Platelet count greater than 150,000/mm^3
No transfusion dependency

Hepatic:

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)

Renal:

Creatinine less than 2.0 mg/dL
No active obstructive hydronephrosis

Other:

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 6 months after study therapy
HIV negative
No active infection requiring oral or IV antibiotics
No human antimurine antibody positivity
No other major medical problems

PRIOR CONCURRENT THERAPY:

Biologic therapy:

See Disease Characteristics
At least 4 weeks since prior growth factors
At least 4 weeks since prior biologic therapy
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

Chemotherapy:

See Disease Characteristics
At least 4 weeks since any prior cytotoxic chemotherapy (6 weeks for nitrosoureas)
No prior fludarabine
No concurrent chemotherapy