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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00064246
First received: July 8, 2003
Last updated: January 24, 2013
Last verified: January 2013
  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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response rate [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Estimated using binomial proportions and their 95% confidence intervals.


Secondary Outcome Measures:
  • 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:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
Radiation: indium In 111 ibritumomab tiuxetan
Given IV
Other Name: IDEC-In2B8
Radiation: yttrium Y 90 ibritumomab tiuxetan
Given IV
Other Names:
  • 90Y ibritumomab tiuxetan
  • IDEC Y2B8
  • Y90 Zevalin
  • Y90-labeled ibritumomab tiuxetan

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
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00064246

Locations
United States, Maryland
AIDS - Associated Malignancies Clinical Trials Consortium
Rockville, Maryland, United States, 20850
Sponsors and Collaborators
Investigators
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, Non-Hodgkin
Lymphoproliferative Disorders
Waldenstrom Macroglobulinemia
Lymphoma, Large B-Cell, Diffuse
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 August 01, 2014