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

This study has been completed.
Sponsor:
Collaborator:
Biogen Idec
Information provided by (Responsible Party):
Julie M Vose, MD, University of Nebraska
ClinicalTrials.gov Identifier:
NCT00031642
First received: March 8, 2002
Last updated: December 13, 2013
Last verified: December 2013
  Purpose

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 Intervention Phase
Lymphoma
Biological: rituximab
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: Phase I/II Study of IDEC-Y2B8 (Zevalin) for Post Transplant Relapses of B-Cell Non-Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by University of Nebraska:

Primary Outcome Measures:
  • Maximum tolerated dose [ Designated as safety issue: Yes ]
  • Safety and efficacy [ Designated as safety issue: Yes ]

Enrollment: 26
Study Start Date: January 2002
Study Completion Date: March 2008
Primary Completion Date: November 2005 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
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
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: NCT00031642

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 Idec
Investigators
Study Chair: Julie M. Vose, MD University of Nebraska
  More Information

Additional Information:
No publications provided

Responsible Party: Julie M Vose, MD, Professor, University of Nebraska
ClinicalTrials.gov Identifier: NCT00031642     History of Changes
Other Study ID Numbers: 535-00, CDR0000069211, NCI-V02-1691
Study First Received: March 8, 2002
Last Updated: December 13, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by 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
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies, Monoclonal
Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 22, 2014