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

Primary Purpose

Post-transplant Lymphoproliferative Disorder, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
rituximab
indium In 111 ibritumomab tiuxetan
yttrium Y 90 ibritumomab tiuxetan
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Post-transplant Lymphoproliferative Disorder

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • AIDS - Associated Malignancies Clinical Trials Consortium

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (rituximab, yttrium Y 90 ibritumomab tiuxetan)

Arm 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.

Outcomes

Primary Outcome Measures

Response rate
Estimated using binomial proportions and their 95% confidence intervals.

Secondary Outcome Measures

Time to response
Analyzed by the Kaplan-Meier non-parametric methods.
Time to progression
Analyzed by the Kaplan-Meier non-parametric methods.
Incidence of toxicity related dose reductions graded according to the NCI CTCAE version 3.0
Presented by severity for each dose group.

Full Information

First Posted
July 8, 2003
Last Updated
January 24, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00064246
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
July 2003 (undefined)
Primary Completion Date
September 2004 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
28 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (rituximab, yttrium Y 90 ibritumomab tiuxetan)
Arm Type
Experimental
Arm 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.
Intervention Type
Biological
Intervention Name(s)
rituximab
Other Intervention Name(s)
IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan
Intervention Description
Given IV
Intervention Type
Radiation
Intervention Name(s)
indium In 111 ibritumomab tiuxetan
Other Intervention Name(s)
IDEC-In2B8
Intervention Description
Given IV
Intervention Type
Radiation
Intervention Name(s)
yttrium Y 90 ibritumomab tiuxetan
Other Intervention Name(s)
90Y ibritumomab tiuxetan, IDEC Y2B8, Y90 Zevalin, Y90-labeled ibritumomab tiuxetan
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Response rate
Description
Estimated using binomial proportions and their 95% confidence intervals.
Time Frame
Up to 4 years
Secondary Outcome Measure Information:
Title
Time to response
Description
Analyzed by the Kaplan-Meier non-parametric methods.
Time Frame
Up to 4 years
Title
Time to progression
Description
Analyzed by the Kaplan-Meier non-parametric methods.
Time Frame
From the date of first study treatment to the first date when progressive disease is documented, assessed up to 4 years
Title
Incidence of toxicity related dose reductions graded according to the NCI CTCAE version 3.0
Description
Presented by severity for each dose group.
Time Frame
Up to 4 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Scadden
Organizational Affiliation
AIDS Associated Malignancies Clinical Trials Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
AIDS - Associated Malignancies Clinical Trials Consortium
City
Rockville
State/Province
Maryland
ZIP/Postal Code
20850
Country
United States

12. IPD Sharing Statement

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

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