Fusion Protein Cytokine Therapy After Rituximab in Treating Patients With B-Cell Non-Hodgkin Lymphoma
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.
Anaplastic Large Cell Lymphoma
Cutaneous B-cell Non-Hodgkin Lymphoma
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
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
Biological: DI-Leu16-IL2 immunocytokine
Other: flow cytometry
Other: immunohistochemistry staining method
Other: pharmacological study
Other: laboratory biomarker analysis
Other: enzyme-linked immunosorbent assay
Genetic: reverse transcriptase-polymerase chain reaction
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of De-Immunized DI-Leu16-IL2 Immunocytokine in Patients With B-Cell Non-Hodgkin Lymphoma|
- Maximum tolerated dose of DI-Leu16-IL2 [ Time Frame: 6 weeks post cycle 1 of treatment ] [ Designated as safety issue: Yes ]
- Optimal biologic dose of DI-Leu16-IL2 [ Time Frame: 6 weeks after final cycle of treatment ] [ Designated as safety issue: Yes ]
- Toxicities associated with the DI-Leu16-IL2 regimen [ Time Frame: 6 weeks after final cycle of treatment ] [ Designated as safety issue: Yes ]
- Immunogenicity as a result of DI-Leu16-IL2 administration [ Time Frame: Within 2 weeks following a 4 week treatment period ] [ Designated as safety issue: No ]
- Pharmacokinetics of DI-Leu16-IL2 administration [ Time Frame: 6 weeks after final cycle of treatment ] [ Designated as safety issue: No ]
- Clinical responses and survival [ Time Frame: Within two weeks following completion of treatment ] [ Designated as safety issue: No ]
|Study Start Date:||January 2008|
|Study Completion Date:||July 2014|
|Primary Completion Date:||July 2014 (Final data collection date for primary outcome measure)|
Experimental: Arm I
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 6-8 weeks for up to a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.
Biological: DI-Leu16-IL2 immunocytokine
Other Names:Biological: rituximab
Other Names:Other: flow cytometry
Correlative studiesOther: immunohistochemistry staining method
Other Name: immunohistochemistryOther: pharmacological study
Other Name: pharmacological studiesOther: laboratory biomarker analysis
Correlative studiesOther: enzyme-linked immunosorbent assay
Other Name: ELISAGenetic: reverse transcriptase-polymerase chain reaction
Other Name: RT-PCR
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00720135
|United States, California|
|City of Hope|
|Duarte, California, United States, 91010|
|Principal Investigator:||Ryotaro Nakamura||City of Hope|