Yttrium Y 90 Ibritumomab Tiuxetan, Etoposide, Cyclophosphamide, and an AHSCT in Non-Hodgkin's Lymphoma Patients
Condition: Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      RATIONALE: Radiolabeled monoclonal antibodies, such as yttrium Y 90 ibritumomab tiuxetan, can
      find cancer cells and carry tumor-killing substances to them without harming normal cells.
      Drugs used in chemotherapy, such as etoposide and cyclophosphamide, work in different ways to
      kill cancer cells or stop them from growing. Giving radiolabeled monoclonal antibodies
      together with etoposide and cyclophosphamide before a peripheral blood stem cell transplant
      may be an effective treatment for non-Hodgkin lymphoma.

      PURPOSE: This phase I/II trial is studying the side effects and best dose of yttrium Y 90
      ibritumomab tiuxetan when given together with etoposide and cyclophosphamide followed by an
      autologous stem cell transplant and to see how well it works in treating patients with
      non-Hodgkin lymphoma.
    

Detailed description: 
      OBJECTIVES:

        -  To evaluate the safety and efficacy of a new preparative regimen of yttrium Y 90
           ibritumomab tiuxetan in combination with high-dose etoposide and cyclophosphamide
           followed by autologous stem cell transplantation (ASCT) for treatment of patients with
           poor-risk, relapsed, or refractory non-Hodgkin lymphoma (NHL).

        -  To determine the maximum tolerated dose of yttrium Y 90 ibritumomab tiuxetan which can
           be given with high-dose etoposide and high-dose cyclophosphamide followed by ASCT in
           patients with NHL.

        -  To perform dosimetry study to estimate the radiation dose delivered to the tumor and
           normal organs.

        -  To evaluate the short-term and long-term complications of this new preparative regimen.

      OUTLINE: This is a phase I does-escalation study of yttrium Y 90 ibritumomab tiuxetan
      followed by an open-label phase II study.

        -  Preparation for transplantation: Peripheral blood stem cells (PBSCs) are collected via
           leukapheresis. Samples are analyzed by cytogenetic studies, immunophenotyping, and gene
           rearrangement. Patients with an adequate number of collected CD34-positive cells (≥ 3
           times 10^6 /kg) proceed to radioimmunotherapy.

        -  Radioimmunotherapy: Patients receive yttrium Y 90 ibritumomab tiuxetan IV on days -21
           and -14. Patients undergo bone marrow biopsy and dose estimation on day -7.

        -  Chemotherapy: Patients receive etoposide IV on day -4 and cyclophosphamide IV over 2
           hours on day -2.

        -  Transplantation: Patients undergo reinfusion of PBSCs on day 1.

        -  Growth factor therapy: Patients receive filgrastim (G-CSF) IV beginning on day 1 and
           continuing until blood counts recover.

      Treatment continues in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed periodically.
    

Intervention name(s): filgrastim; cyclophosphamide; etoposide; AHSCT; yttrium Y 90 ibritumomab tiuxetan
Intervention type(s): Biological; Drug; Drug; Procedure; Radiation
Other intervention name(s): Cytoxan; VP-16; autologous hematopoietic stem cell transplantation; Zevalin
Intervention MeSH terms: Cyclophosphamide; Etoposide
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; recurrent adult diffuse large cell lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult diffuse small cleaved cell lymphoma; recurrent adult immunoblastic large cell lymphoma; recurrent mantle cell lymphoma; stage III grade 1 follicular lymphoma; stage III grade 2 follicular lymphoma; stage III grade 3 follicular lymphoma; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; stage IV grade 3 follicular lymphoma; stage III adult diffuse large cell lymphoma; stage III adult diffuse mixed cell lymphoma; stage III adult diffuse small cleaved cell lymphoma; stage IV adult diffuse large cell lymphoma; stage IV adult diffuse mixed cell lymphoma; stage IV adult diffuse small cleaved cell lymphoma; stage III mantle cell lymphoma; stage IV mantle cell lymphoma; stage III adult immunoblastic large cell lymphoma; stage IV adult immunoblastic large cell lymphoma