Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab in Treating Patients With Post-Transplant Lymphoproliferative Disorder
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Purpose
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
| Condition | Intervention | Phase |
|---|---|---|
|
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 |
Biological: rituximab Radiation: indium In 111 ibritumomab tiuxetan Radiation: yttrium Y 90 ibritumomab tiuxetan |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase I/II Study: Zevalin Radioimmunotherapy for Patients With Post Transplant Lymphoproliferative Disease Following Solid Organ Transplantation |
- Response rate [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]Estimated using binomial proportions and their 95% confidence intervals.
- Time to response [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]Analyzed by the Kaplan-Meier non-parametric methods.
- Time to progression [ Time Frame: From the date of first study treatment to the first date when progressive disease is documented, assessed up to 4 years ] [ Designated as safety issue: No ]Analyzed by the Kaplan-Meier non-parametric methods.
- Incidence of toxicity related dose reductions graded according to the NCI CTCAE version 3.0 [ Time Frame: Up to 4 years ] [ Designated as safety issue: Yes ]Presented by severity for each dose group.
| Enrollment: | 28 |
| Study Start Date: | July 2003 |
| Primary Completion Date: | September 2004 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 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. |
Biological: rituximab
Given IV
Other Names:
Radiation: indium In 111 ibritumomab tiuxetan
Given IV
Other Name: IDEC-In2B8
Radiation: yttrium Y 90 ibritumomab tiuxetan
Given IV
Other Names:
|
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| United States, Maryland | |
| AIDS - Associated Malignancies Clinical Trials Consortium | |
| Rockville, Maryland, United States, 20850 | |
| Principal Investigator: | David Scadden | AIDS Associated Malignancies Clinical Trials Consortium |
More Information
No publications provided
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00064246 History of Changes |
| Other Study ID Numbers: | NCI-2012-02721, AMC-037, U01CA070019, CDR0000310158 |
| Study First Received: | July 8, 2003 |
| Last Updated: | January 24, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Burkitt Lymphoma Lymphoma Lymphoma, Large B-Cell, Diffuse Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Waldenstrom Macroglobulinemia Epstein-Barr Virus Infections Herpesviridae Infections DNA Virus Infections Virus Diseases Tumor Virus Infections Neoplasms by Histologic Type Neoplasms Lymphoma, B-Cell Neoplasms, Experimental |
Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Neoplasms, Plasma Cell Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Antibodies, Monoclonal Rituximab Immunologic Factors Physiological Effects of Drugs |
ClinicalTrials.gov processed this record on June 17, 2013