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

University of Nebraska

Status and phase

Completed

Phase 2

Phase 1

Conditions

Lymphoma

Treatments

Radiation: yttrium Y 90 ibritumomab tiuxetan

Biological: rituximab

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00031642

0535-00-FB

CDR0000069211 (Registry Identifier)

NCI-V02-1691

Details and patient eligibility

About

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.

Full 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.

Enrollment

26 patients

Sex

All

Ages

19 to 120 years old

Volunteers

No Healthy Volunteers

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