MedPath

Monoclonal Antibody Therapy in Relapsed Non-Hodgkin's After Chemotherapy and Autologous Stem Cell Transplantation

Phase 1
Completed
Conditions
Lymphoma
Registration Number
NCT00031642
Lead Sponsor
University of Nebraska
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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
26
Inclusion Criteria
  • 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

    o 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

    o More than 2 cm bidimensionally

  • 19 years of age and over

  • Performance status WHO 0-2

  • Life expectancy at least 3 months

  • Absolute neutrophil count greater than 1,500/mm^3

  • Platelet count greater than 150,000/mm^3

  • 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)

  • Creatinine less than 2.0 mg/dL

  • Fertile patients must use effective contraception during and for 6 months after study therapy

  • HIV negative

  • At least 4 weeks since prior growth factors

  • At least 4 weeks since prior biologic therapy

  • At least 4 weeks since any prior cytotoxic chemotherapy (6 weeks for nitrosoureas)

  • At least 4 weeks since prior radiotherapy

  • Recovered from all prior therapy

  • At least 4 weeks since prior immunosuppressants

Exclusion Criteria
  • No active CNS lymphoma
  • No HIV- or AIDS-related lymphoma
  • No transfusion dependency
  • No active obstructive hydronephrosis
  • Not pregnant or nursing/negative pregnancy test
  • No active infection requiring oral or IV antibiotics
  • No human antimurine antibody positivity
  • No other major medical problems
  • 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
  • No prior fludarabine
  • No concurrent chemotherapy
  • No concurrent steroids except as maintenance for non-cancerous disease
  • No prior pelvic radiotherapy
  • No prior radiotherapy to more than 25% of estimated bone marrow reserve
  • No concurrent external beam radiotherapy
  • No other concurrent investigational drugs
  • No other concurrent anti-cancer therapy

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Primary Outcome Measures
NameTimeMethod
Maximum tolerated dose
Safety and efficacy
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Eppley Cancer Center at University of Nebraska Medical Center

🇺🇸

Omaha, Nebraska, United States

© Copyright 2025. All Rights Reserved by MedPath