Brief Title
Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab in Treating Patients With Post-Transplant Lymphoproliferative Disorder
Official Title
A Phase I/II Study: Zevalin Radioimmunotherapy for Patients With Post Transplant Lymphoproliferative Disease Following Solid Organ Transplantation
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.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Response rate
Secondary Outcome
Time to response
Condition
Post-transplant Lymphoproliferative Disorder
Intervention
rituximab
Study Arms / Comparison Groups
Treatment (rituximab, yttrium Y 90 ibritumomab tiuxetan)
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
28
Start Date
July 2003
Primary Completion Date
September 2004
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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
David Scadden, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00064246
Organization ID
NCI-2012-02721
Secondary IDs
AMC-037
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Study Sponsor
David Scadden, Principal Investigator, AIDS Associated Malignancies Clinical Trials Consortium
Verification Date
January 2013