Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab in Treating Patients With Post-Transplant Lymphoproliferative Disorder

NCT ID: NCT00064246

Last Updated: 2013-01-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-07-31

Brief Summary

Phase I/II trial to study the effectiveness of combining yttrium Y 90 ibritumomab tiuxetan with rituximab in treating patients who have localized or recurrent lymphoproliferative disorder after an organ transplant. Monoclonal antibodies such as yttrium Y 90 ibritumomab tiuxetan and rituximab can locate cancer cells and either kill them or deliver radioactive cancer-killing substances to them without harming normal cells

Detailed Description

OBJECTIVES:

I. Determine the safety and tolerability of yttrium Y 90 ibritumomab tiuxetan (IDEC-Y2B8) in patients with post-transplant lymphoproliferative disorder.

II. Determine the safety and toxicity profile of IDEC-Y2B8 and rituximab in these patients.

III. Correlate the Epstein-Barr virus viral load with response and relapse in patients treated with this regimen.

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

Phase I: Patients receive rituximab IV and indium In 111 ibritumomab tiuxetan IV over 10 minutes on day 1. Patients undergo 2 (or 3 if needed) imaging scans between days 1-6. In the absence of altered biodistribution, patients receive rituximab IV followed within 4 hours by IDEC-Y2B8 IV over 10 minutes on day 8.Cohorts of 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 no more than 1 of 6 patients experience dose-limiting toxicity.

Phase II: Patients receive treatment as in phase I at the MTD of IDEC-Y2B8. Patients are followed monthly for 3 months, every 3 months for 2 years, and then every 6 months for 2 years.

Conditions

Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Waldenström Macroglobulinemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (rituximab, yttrium Y 90 ibritumomab tiuxetan)

Phase I: Patients receive rituximab IV and indium In 111 ibritumomab tiuxetan IV over 10 minutes on day 1. Patients undergo 2 (or 3 if needed) imaging scans between days 1-6. In the absence of altered biodistribution, patients receive rituximab IV followed within 4 hours by IDEC-Y2B8 IV over 10 minutes on day 8.

Phase II: Patients receive treatment as in phase I at the MTD of IDEC-Y2B8. Patients are followed monthly for 3 months, every 3 months for 2 years, and then every 6 months for 2 years.

Group Type: EXPERIMENTAL

rituximab

Intervention Type: BIOLOGICAL

Given IV

indium In 111 ibritumomab tiuxetan

Intervention Type: RADIATION

Given IV

yttrium Y 90 ibritumomab tiuxetan

Intervention Type: RADIATION

Given IV

Interventions

rituximab

Given IV

Intervention Type: BIOLOGICAL

indium In 111 ibritumomab tiuxetan

Given IV

Intervention Type: RADIATION

yttrium Y 90 ibritumomab tiuxetan

Given IV

Intervention Type: RADIATION

Other Intervention Names

IDEC-C2B8; IDEC-C2B8 monoclonal antibody; Mabthera; MOAB IDEC-C2B8; Rituxan; IDEC-In2B8; 90Y ibritumomab tiuxetan; IDEC Y2B8; Y90 Zevalin; Y90-labeled ibritumomab tiuxetan

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed post-transplant lymphoproliferative disorder (PTLD) of 1 of the following stages:

• Stage III or IV
• Localized (not amenable to localized radiotherapy or excision)
• Recurrent
• The following histologies* are eligible:

• Polyclonal PTLD
• Monoclonal PTLD
• Diffuse large B-cell non-Hodgkin's lymphoma (NHL)
• Lymphoplasmacytic NHL
• Burkitt/Burkitt-like NHL
• Must not have completely responded during OR progressed after prior rituximab with or without chemotherapy

• No history of rapid disease progression while receiving prior chemotherapy
• Measurable disease
• Must have less than 25% bone marrow involvement with lymphoma
• Prior solid organ transplantation required
• Evaluation of malignant cells for Epstein-Barr virus (EBV) required

• EBV positive or negative allowed
• No pleural effusion
• No CNS lymphoma, including leptomeningeal disease
• No pulmonary involvement by NHL in patients with prior lung transplantation
• No HIV or AIDS-related lymphoma
• No hypocellular bone marrow (i.e., less than 15% cellularity)
• No marked reduction in bone marrow precursors of one or more cell lines (i.e., granulocytic, megakaryocytic, or erythroid)
• Performance status - Karnofsky 50-100%
• At least 3 months
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 150,000/mm^3
• Bilirubin no greater than 2.5 mg/dL
• Creatinine no greater than 2.5 mg/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after study participation
• HIV negative
• No serious nonmalignant disease or infection that would compromise study objectives
• No presence of antimurine antibody reactivity
• No other concurrent active malignancy requiring therapy
• More than 2 weeks since prior filgrastim (G-CSF) or sargramostim (GM-CSF)
• More than 6 weeks since prior rituximab
• No prior allogeneic bone marrow or hematopoietic stem cell transplantation
• No prior radioimmunotherapy for NHL
• More than 4 weeks since prior chemotherapy
• See Biologic therapy
• No prior radiotherapy to more than 25% of active bone marrow (involved field or regional)
• More than 4 weeks since prior major surgery except diagnostic surgery
• No other concurrent anticancer therapy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Scadden

Role: PRINCIPAL_INVESTIGATOR

AIDS Associated Malignancies Clinical Trials Consortium

Locations

AIDS - Associated Malignancies Clinical Trials Consortium

Rockville, Maryland, United States

Countries

United States

Other Identifiers

AMC-037

Identifier Type: -

Identifier Source: secondary_id

U01CA070019

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000310158

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-02721

Identifier Type: -

Identifier Source: org_study_id