Fusion Protein Cytokine Therapy After Rituximab in Treating Patients With B-Cell Non-Hodgkin Lymphoma

NCT00720135 | Completed Phase 1 DMC

• 4 other identifiers: 03131NCI-2010-01228CDR0000598679P50CA107399
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose of DI-Leu16-IL2

  6 weeks post cycle 1 of treatment

• Optimal biologic dose of DI-Leu16-IL2

  6 weeks after final cycle of treatment

• Toxicities associated with the DI-Leu16-IL2 regimen

  6 weeks after final cycle of treatment

Secondary Outcomes (3)

• Immunogenicity as a result of DI-Leu16-IL2 administration

  Within 2 weeks following a 4 week treatment period

• Pharmacokinetics of DI-Leu16-IL2 administration

  6 weeks after final cycle of treatment

• Clinical responses and survival

  Within two weeks following completion of treatment

Study Arms (1)

Arm I

EXPERIMENTAL

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; Biological: rituximab; 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

Interventions

DI-Leu16-IL2 immunocytokine BIOLOGICAL

Given IV

Also known as: de-immunized anti-CD20-IL-2 immunocytokine DI-Leu16-IL-2, DI-Leu16-IL-2

Arm I

rituximab BIOLOGICAL

Given IV

Also known as: C2B8 Monoclonal Antibody, IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan

Arm I

flow cytometry OTHER

Correlative studies

Arm I

immunohistochemistry staining method OTHER

Correlative studies

Also known as: immunohistochemistry

Arm I

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Arm I

laboratory biomarker analysis OTHER

Correlative studies

Arm I

enzyme-linked immunosorbent assay OTHER

Correlative studies

Also known as: ELISA

Arm I

reverse transcriptase-polymerase chain reaction GENETIC

Correlative studies

Also known as: RT-PCR

Arm I

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with CD20-expressing B cell NHL that is relapsed or refractory to standard therapy; CLL/SLL with peripheral blood leukemia/lymphoma cells and high-grade lymphomas (i.e., lymphoblastic lymphoma/Burkitt lymphoma) are excluded
• Patients must have received prior Rituxan
• Measurable disease; in the absence of lymphadenopathy, splenomegaly with defects or measurable extramedullary disease is acceptable; however, bone marrow involvement alone will not be included in the study
• Age \>=18 years and \<=65 physiologic years of age
• KPS \>= 70%
• Life expectancy \>= 12 weeks
• Serum creatinine =\< 1.5 mg/dl
• Total WBC \>= 3000/ul or absolute neutrophil count (ANC) \>= 1000/ul
• Lymphocyte count \>= 0.2 x 10\^3/ul
• Platelet count \>= 75,000/ul
• Hematocrit \>= 25% or hemoglobin \>= 9 g/100 ml
• Alanine aminotransferase (ALT) =\< 2.5 x UNL
• Aspartate aminotransferase (AST) =\< 2.5 x UNL
• Total bilirubin (TBili) \< 1.5 x UNL
• Sodium, potassium, and phosphorus within normal limits

You may not qualify if:

• Evidence of CNS lymphoma or lymphomatous meningitis
• Prior treatment with IL-2
• Type I hypersensitivity or anaphylactic reactions to murine proteins or to previous infusion of rituximab
• Pregnant or lactating female
• An immediate need for palliative radiotherapy or systemic corticosteroid therapy
• Known intercurrent infections (including hepatitis C virus \[HCV\] and HIV or other conditions), or clinical evidence of these conditions
• Actively infected with or chronic carriers of hepatitis B virus (HBV) as demonstrated by positive hepatitis B core antibody (HbcHb) or hepatitis B surface antigen (HbsAg); (subjects who are sero-positive only, i.e., surface antibody positive \[HbsAg\], are permitted)
• Other significant active infection
• Major surgery, chemotherapy, investigational agent, or radiation within 30 days of Day 1
• Uncontrolled hypertension (diastolic \>= 100 mmHg) or hypotension (systolic =\< 90 mmHg)
• History of repeated and clinically relevant episodes of syncope or other paroxysmal, ventricular, or other significant arrhythmias
• On ECG: a marked baseline prolongation of QT/QTc interval (\> grade 2 QTc interval \> 470 milliseconds)
• History of medically significant ascites requiring repetitive paracentesis
• Previous diagnosis of Addison's disease
• Previous diagnosis of autoimmune disease (exceptions: subjects with autoimmune thyroiditis or vitiligo may be enrolled)

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Lymphoma, Large-Cell, Anaplastic; Intraocular Lymphoma; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Non-Hodgkin; Lymphoma, Follicular; Waldenstrom Macroglobulinemia

Interventions

Rituximab; Flow Cytometry; Immunohistochemistry; Enzyme-Linked Immunosorbent Assay; Reverse Transcriptase Polymerase Chain Reaction

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Eye Neoplasms; Neoplasms by Site; Lymphoma, B-Cell; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical; Investigative Techniques; Histocytochemistry; Histological Techniques; Immunologic Techniques; Immunoenzyme Techniques; Immunoassay; Immunosorbent Techniques; Molecular Probe Techniques; Polymerase Chain Reaction; Nucleic Acid Amplification Techniques; Genetic Techniques

Study Officials

• Ryotaro Nakamura

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2008
• First Posted: July 22, 2008
• Study Start: January 1, 2008
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: June 8, 2015

Record last verified: 2015-06

Locations

US (1)