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

Sponsors and Collaborators:	AIDS Associated Malignancies Clinical Trials Consortium National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00064246

Purpose

RATIONALE: 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.

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.

Condition	Intervention	Phase
Lymphoma Lymphoproliferative Disorder	Biological: rituximab Radiation: yttrium Y 90 ibritumomab tiuxetan	Phase I Phase II

Study Type:	Interventional
Study Design:	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:

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Rituximab Ibritumomab tiuxetan

U.S. FDA Resources

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

Detailed Description:

OBJECTIVES:

Determine the safety and tolerability of yttrium Y 90 ibritumomab tiuxetan (IDEC-Y2B8) in patients with post-transplant lymphoproliferative disorder.
Determine the safety and toxicity profile of IDEC-Y2B8 and rituximab in these patients.
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.

PROJECTED ACCRUAL: A total of 13-28 patients will be accrued for this study within 2 years.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

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 NOTE: *Must be B-cell and CD20+
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)

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

Karnofsky 50-100%

Life expectancy

At least 3 months

Hematopoietic

Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 150,000/mm^3

Hepatic

Bilirubin no greater than 2.5 mg/dL

Renal

Creatinine no greater than 2.5 mg/dL

Other

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

PRIOR CONCURRENT THERAPY:

Biologic therapy

See Disease Characteristics
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

Chemotherapy

See Disease Characteristics
More than 4 weeks since prior chemotherapy

Endocrine therapy

Not specified

Radiotherapy

See Biologic therapy
No prior radiotherapy to more than 25% of active bone marrow (involved field or regional)

Surgery

See Disease Characterisics
More than 4 weeks since prior major surgery except diagnostic surgery

Other

No other concurrent anticancer therapy

Contacts and Locations

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

Sponsors and Collaborators

AIDS Associated Malignancies Clinical Trials Consortium

National Cancer Institute (NCI)

Investigators

Study Chair:

David T. Scadden, MD

Massachusetts General Hospital

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000310158, AMC-037
Study First Received:	July 8, 2003
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00064246 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

recurrent adult diffuse large cell lymphoma
recurrent adult Burkitt lymphoma
stage III adult diffuse large cell lymphoma
stage III adult Burkitt lymphoma

stage IV adult diffuse large cell lymphoma
stage IV adult Burkitt lymphoma
post-transplant lymphoproliferative disorder
Waldenstrom macroglobulinemia

Study placed in the following topic categories:

Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Immunologic Factors
Rituximab
Recurrence
Antibodies, Monoclonal
Lymphatic Diseases
Post-transplant Lymphoproliferative Disease
Burkitt's Lymphoma

Waldenstrom Macroglobulinemia
Antibodies
Burkitt Lymphoma
Antirheumatic Agents
Lymphoproliferative Disorders
Lymphoma, Large-cell
Lymphoma
Immunoglobulins

Additional relevant MeSH terms:

Disease
Neoplasms by Histologic Type
Immunoproliferative Disorders
Immune System Diseases
Immunologic Factors
Antineoplastic Agents
Rituximab
Physiological Effects of Drugs
Pharmacologic Actions

Antibodies, Monoclonal
Lymphatic Diseases
Neoplasms
Pathologic Processes
Therapeutic Uses
Antirheumatic Agents
Lymphoproliferative Disorders
Lymphoma

ClinicalTrials.gov processed this record on July 02, 2009