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

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

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.

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