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

January 24, 2013 updated by: National Cancer Institute (NCI)

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

28

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Rockville, Maryland, United States, 20850
        • AIDS - Associated Malignancies Clinical Trials Consortium

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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:
  • Rituxan
  • Mabthera
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • MOAB IDEC-C2B8
Radiation: yttrium Y 90 ibritumomab tiuxetan
Given IV
Other Names:
  • 90Y ibritumomab tiuxetan
  • IDEC Y2B8
  • Y90 Zevalin
  • Y90-labeled ibritumomab tiuxetan
Radiation: indium In 111 ibritumomab tiuxetan
Given IV
Other Names:
  • IDEC-In2B8

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response rate
Time Frame: Up to 4 years
Estimated using binomial proportions and their 95% confidence intervals.
Up to 4 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to response
Time Frame: Up to 4 years
Analyzed by the Kaplan-Meier non-parametric methods.
Up to 4 years
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
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
Incidence of toxicity related dose reductions graded according to the NCI CTCAE version 3.0
Time Frame: Up to 4 years
Presented by severity for each dose group.
Up to 4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: David Scadden, AIDS Associated Malignancies Clinical Trials Consortium

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2003

Primary Completion (Actual)

September 1, 2004

Study Registration Dates

First Submitted

July 8, 2003

First Submitted That Met QC Criteria

July 8, 2003

First Posted (Estimate)

July 9, 2003

Study Record Updates

Last Update Posted (Estimate)

January 25, 2013

Last Update Submitted That Met QC Criteria

January 24, 2013

Last Verified

January 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-02721
  • U01CA070019 (U.S. NIH Grant/Contract)
  • AMC-037
  • CDR0000310158 (Registry Identifier: PDQ (Physician Data Query))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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