Fusion Protein Cytokine Therapy After Rituximab in Treating Patients With B-Cell Non-Hodgkin Lymphoma
Condition: Anaplastic Large Cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia
MeSH terms: Lymphoma; Lymphoma, Follicular; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma, B-Cell, Marginal Zone; Waldenstrom Macroglobulinemia; Lymphoma, Large-Cell, Anaplastic; Lymphomatoid Granulomatosis; Intraocular Lymphoma; Recurrence
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: Biological therapies, such as fusion protein cytokine therapy, may stimulate the
      immune system in different ways and stop cancer cells from growing. Monoclonal antibodies,
      such as rituximab, can block cancer growth in different ways. Some block the ability of
      cancer cells to grow and spread. Others find cancer cells and help kill them or carry
      cancer-killing substances to them. Giving fusion protein cytokine therapy together with
      rituximab may kill more cancer cells.

      PURPOSE: This phase I trial is studying the side effects and best dose of fusion protein
      cytokine therapy when given after rituximab in treating patients with B-cell non-Hodgkin
      lymphoma.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To determine the maximum tolerated dose (MTD) of DI-Leu16-IL2 (DI-Leu16-IL2
      immunocytokine) following peripheral blood B cell depletion with rituximab in patients with
      B-cell NHL.

      II. To investigate the optimal biological dose (OBD) of DI-Leu16-IL2 following peripheral
      blood B cell depletion with rituximab in patients with B-cell NHL, which may differ from the
      MTD.

      III. To describe the toxicities associated with the proposed DI-Leu16-IL2 regimen.

      SECONDARY OBJECTIVES:

      I. To evaluate the immunogenicity as measured by the induction of DI-Leu16-IL2-specific
      antibodies.

      II. To evaluate the pharmacokinetics of DI-Leu16-IL2. III. To document any clinical responses
      associated with the proposed therapy and survival endpoints of the enrolled patients.

      OUTLINE: This is a dose-escalation study of DI-Leu16-IL2 immunocytokine.

      Patients receive DI-Leu16-IL2 immunocytokine IV over 4 hours on 4 consecutive Wednesdays.

      Patients with detectable CD20-positive B-cells pretreatment also receive rituximab IV on 4
      consecutive Tuesdays.

      Treatment repeats every 6 weeks for up to 4 courses in the absence of disease progression or
      unacceptable toxicity.

      After completion of study treatment, patients are followed up periodically for 5 years.
    

Intervention name(s): DI-Leu16-IL2 immunocytokine; rituximab; flow cytometry; immunohistochemistry staining method; pharmacological study; laboratory biomarker analysis; enzyme-linked immunosorbent assay; reverse transcriptase-polymerase chain reaction
Intervention type(s): Biological; Biological; Other; Other; Other; Other; Other; Genetic
Intervention description(s): Given IV; Given IV; Correlative studies; Correlative studies; Correlative studies; Correlative studies; Correlative studies; Correlative studies
Other intervention name(s): de-immunized anti-CD20-IL-2 immunocytokine DI-Leu16-IL-2; DI-Leu16-IL-2; C2B8 Monoclonal Antibody; IDEC-C2B8; IDEC-C2B8 monoclonal antibody; Mabthera; MOAB IDEC-C2B8; Rituxan; immunohistochemistry; pharmacological studies; ELISA; RT-PCR
Intervention MeSH terms: Rituximab; Antineoplastic Agents, Immunological; Interleukin-2; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment