Monoclonal Antibody Therapy in Treating Patients With Non-Hodgkin's Lymphoma That Has Relapsed After High-Dose Chemotherapy and Autologous Stem Cell Transplantation

Study Description

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Brief Summary:

RATIONALE: Monoclonal antibodies such as rituximab can locate cancer cells and deliver cancer-killing substances to them without harming normal cells. Radiolabeled monoclonal antibodies can locate and deliver radioactive cancer-killing substances.

PURPOSE: Phase I/II trial to study the effectiveness of combining radiolabeled monoclonal antibodies with rituximab in treating patients who have non-Hodgkin's lymphoma that has not responded to high-dose chemotherapy and autologous stem cell transplantation.

Condition or disease	Intervention/treatment	Phase
Lymphoma	Biological: rituximab; Radiation: yttrium Y 90 ibritumomab tiuxetan	Phase 1; Phase 2

Detailed Description:

OBJECTIVES:

• Determine the maximum tolerated dose of yttrium Y 90-labeled ibritumomab tiuxetan when administered with rituximab in patients with B-cell non-Hodgkin's lymphoma who have relapsed after high-dose chemotherapy and autologous hematopoietic stem cell transplantation.
• Determine the safety and efficacy of this regimen in these patients.

OUTLINE: This is a dose-escalation study of yttrium Y 90-labeled ibritumomab tiuxetan (IDEC-Y2B8).

• Phase I: Patients receive rituximab IV over 4-6 hours followed by indium In 111-labeled ibritumomab tiuxetan (IDEC-In2B8) IV over 10 minutes on day 0. Patients receive rituximab IV again on day 7 followed by IDEC-Y2B8 IV over 10 minutes.

Cohorts of 3-6 patients receive escalating doses of IDEC-Y2B8 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 3 of 6 patients experience dose-limiting toxicity.

• Phase II: Once the MTD is determined, 58 additional patients are treated at that dose level as in phase I.

Patients are followed at 6 weeks, every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 78 patients (20 for phase I and 58 for phase II) will be accrued for this study within 2 years.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	26 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Phase I/II Study of IDEC-Y2B8 (Zevalin) for Post Transplant Relapses of B-Cell Non-Hodgkin's Lymphoma
Study Start Date :	January 2002
Actual Primary Completion Date :	November 2005
Actual Study Completion Date :	March 2008

Arms and Interventions

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Outcome Measures

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Primary Outcome Measures :

1. Maximum tolerated dose
2. Safety and efficacy

Eligibility Criteria

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Ages Eligible for Study:	19 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of relapsed B-cell non-Hodgkin's lymphoma (NHL) after high-dose chemotherapy and autologous stem cell transplantation

• Less than 25% bone marrow involvement with NHL as evidenced by unilateral or bilateral biopsy within the past 6 weeks

  • Bone marrow biopsy should demonstrate 15-20% of cellular space occupied by normal hematopoiesis

• CD20 antigen expression in tumor tissue within the past year as evidenced by 1 of the following:

  • Immunoperoxidase stains of tissue showing positive reactivity with L26 antibody
  • Flow cytometry studies

• Measurable disease

  • More than 2 cm bidimensionally
• No active CNS lymphoma
• No HIV- or AIDS-related lymphoma

PATIENT CHARACTERISTICS:

Age:

• 19 and over

Performance status:

• WHO 0-2

Life expectancy:

• At least 3 months

Hematopoietic:

• Absolute neutrophil count greater than 1,500/mm^3
• Platelet count greater than 150,000/mm^3
• No transfusion dependency

Hepatic:

• Bilirubin less than 2.0 mg/dL
• SGOT or SGPT no greater than 2.5 times upper limit of normal (unless due to lymphomatous infiltration of the liver)

Renal:

• Creatinine less than 2.0 mg/dL
• No active obstructive hydronephrosis

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after study therapy
• HIV negative
• No active infection requiring oral or IV antibiotics
• No human antimurine antibody positivity
• No other major medical problems

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics
• At least 4 weeks since prior growth factors
• At least 4 weeks since prior biologic therapy
• No dependency on hematopoietic growth factors (e.g., epoetin alfa, interleukin-11, filgrastim [G-CSF], or sargramostim [GM-CSF])
• No prior radioimmunotherapy
• No other concurrent biologic therapy of any kind

Chemotherapy:

• See Disease Characteristics
• At least 4 weeks since any prior cytotoxic chemotherapy (6 weeks for nitrosoureas)
• No prior fludarabine
• No concurrent chemotherapy

Endocrine therapy:

• No concurrent steroids except as maintenance for non-cancerous disease

Radiotherapy:

• See Biologic therapy
• At least 4 weeks since prior radiotherapy
• No prior pelvic radiotherapy
• No prior radiotherapy to more than 25% of estimated bone marrow reserve
• No concurrent external beam radiotherapy

Surgery:

• Not specified

Other:

• Recovered from all prior therapy
• At least 4 weeks since prior immunosuppressants
• No other concurrent investigational drugs
• No other concurrent anti-cancer therapy

Contacts and Locations

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Locations

United States, Nebraska
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198-7680

Sponsors and Collaborators

University of Nebraska

Biogen

Investigators

Study Chair:	Julie M. Vose, MD	University of Nebraska

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Julie M Vose, MD, Professor, University of Nebraska
ClinicalTrials.gov Identifier:	NCT00031642 History of Changes
Other Study ID Numbers:	535-00; CDR0000069211 ( Registry Identifier: PDQ (Physician Data Query) ); NCI-V02-1691
First Posted:	January 27, 2003
Last Update Posted:	December 17, 2013
Last Verified:	December 2013

Keywords provided by Julie M Vose, MD, University of Nebraska:

recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; recurrent adult diffuse small cleaved cell lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult diffuse large cell lymphoma; recurrent adult immunoblastic large cell lymphoma	recurrent adult Burkitt lymphoma; recurrent mantle cell lymphoma; recurrent marginal zone lymphoma; recurrent small lymphocytic lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; splenic marginal zone lymphoma

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders	Immune System Diseases; Rituximab; Antibodies, Monoclonal; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents