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

Phase 1

Completed

• Conditions: 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
• Interventions: Biological: rituximab; Radiation: indium In 111 ibritumomab tiuxetan; Radiation: yttrium Y 90 ibritumomab tiuxetan

• Registration Number: NCT00064246
• Lead Sponsor: National Cancer Institute (NCI)

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 Timeline

• Study Start: 2003-07
• Study First Submitted: 2003-07-08
• Study First Submitted QC: 2003-07-08
• Study First Posted: 2003-07-09
• Primary Completion: 2004-09
• Status Verified: 2013-01
• Last Update Submitted: 2013-01-24
• Last Update Posted: 2013-01-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 28

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (rituximab, yttrium Y 90 ibritumomab tiuxetan)	rituximab	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.
Treatment (rituximab, yttrium Y 90 ibritumomab tiuxetan)	indium In 111 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.
Treatment (rituximab, yttrium Y 90 ibritumomab tiuxetan)	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.

Primary Outcome Measures

Name	Time	Method
Response rate	Up to 4 years	Estimated using binomial proportions and their 95% confidence intervals.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

AIDS - Associated Malignancies Clinical Trials Consortium; 🇺🇸 Rockville, Maryland, United States