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

Recurrent Adult Diffuse Large Cell Lymphoma Clinical Trial

Official title:

A Phase I/II Study: Zevalin Radioimmunotherapy for Patients With Post Transplant Lymphoproliferative Disease Following Solid Organ Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00064246
• Other study ID #: NCI-2012-02721
• Secondary ID: AMC-037U01CA0700
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: July 8, 2003
• Last updated: January 24, 2013
• Start date: July 2003

Study information

• Verified date: January 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. primary completion date: September 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Burkitt Lymphoma
• Lymphoma
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Non-Hodgkin
• Lymphoproliferative Disorders
• 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
• Waldenstrom Macroglobulinemia
• Waldenström Macroglobulinemia

Intervention

Biological:
• rituximab
Given IV

Radiation:
• indium In 111 ibritumomab tiuxetan
Given IV
• yttrium Y 90 ibritumomab tiuxetan
Given IV

Locations

Country	Name	City	State
United States	AIDS - Associated Malignancies Clinical Trials Consortium	Rockville	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate	Estimated using binomial proportions and their 95% confidence intervals.	Up to 4 years	No
Secondary	Time to response	Analyzed by the Kaplan-Meier non-parametric methods.	Up to 4 years	No
Secondary	Time to progression	Analyzed by the Kaplan-Meier non-parametric methods.	From the date of first study treatment to the first date when progressive disease is documented, assessed up to 4 years	No
Secondary	Incidence of toxicity related dose reductions graded according to the NCI CTCAE version 3.0	Presented by severity for each dose group.	Up to 4 years	Yes