Safety and Efficacy Study of Immunotherapy With Rituximab and Interleukin-2 in Patients With Non-Hodgkin's Lymphoma

NCT ID: NCT00994643

Last Updated: 2025-04-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-02-05
• Study Completion Date: 2015-06-25

Brief Summary

This is a study to see if maintenance therapy with low dose interleukin-2 (IL-2) and rituximab can delay or prevent recurrences in patients with high risk Non-Hodgkin's Lymphoma (NHL). IL-2 is a naturally occurring cytokine in our immune system which may enhance the activity of a known therapeutic agent rituximab, a monoclonal antibody against CD-20, in the setting of NHL.

Detailed Description

Interleukin 2 (IL-2) is a naturally circulating cytokine produced by immune cells including T cells, dendritic cells and thymic cells. IL-2 is an integral part of T cell proliferation, autoimmunity and self-tolerance. Low dose IL-2 has been studied as maintenance therapy following autologous stem cell transplantation in Non-Hodgkin's Lymphoma. One early study showed that low dose IL-2 at dose of 3 million units per m2 twice a week for one year increased the activity and absolute number of natural killer (NK) cells which are a type of cytotoxic lymphocyte that is a major component of our innate immune system. More importantly, this dose of IL-2 prolonged time to progression in 9 patients with residual disease after autologous transplant and induced sustained complete remissions in two more patients. NK cells are involved in tumor killing via antibody dependent cell cytotoxicity, release of cytotoxic granules causing direct tumor killing and expression of ligands that trigger apoptosis or programmed cell death. In that study, no changes were seen in regulatory T cells which have been recently found to exert an inhibitory effect on NK cell function and hence limit the NK cell's ability to exert an anti-tumor effect.2,5 Because both regulatory T cells and NK cells express the IL-2 receptor, higher doses of IL-2 administration (14MIU SQ thrice weekly) would expand both populations of cells which may explain the lack of benefit seen in other clinical studies. At lower doses of 3MIU SQ twice weekly used in the earlier study, we anticipate selective upregulation of NK cells without effecting regulatory T cells.

Rituximab is a monoclonal antibody against CD20 antigen that is expressed in most B cell lymphomas. It is commonly used in the treatment of B cell lymphomas either alone or in combination with other therapy. It has been used as part of initial treatment after diagnosis as well as re-treatment if lymphoma recurred. It has also been studied as maintenance therapy in relapsed or resistant follicular lymphoma showing that rituximab delayed disease progression compared to the group who did not receive maintenance rituximab.11 The mechanism of action of rituximab includes complement mediated cytotoxicity, antibody dependent cellular cytotoxicity, induction of apoptosis and sensitization of cancer cells to cytotoxic chemotherapy. Antibody dependent cellular cytotoxicity is mediated by NK cells, macrophages and monocytes.13 The purpose of this study is to determine if the combination of low dose IL-2 plus rituximab is more effective than low dose IL-2 alone after primary or salvage therapy.

Conditions

High Risk Non-Hodgkin's Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (Interleukin Therapy, Monoclonal Antibody)

Patients receive interleukin-2 SC twice weekly and rituximab IV once weekly in weeks 5-8 and 25-28. Courses repeat every 4 weeks for up to 7 months in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: BIOLOGICAL

Given IV

Interleukin-2

Intervention Type: BIOLOGICAL

Given SC

Interventions

Rituximab

Given IV

Intervention Type: BIOLOGICAL

Interleukin-2

Given SC

Intervention Type: BIOLOGICAL

Other Intervention Names

C2B8 Monoclonal Antibody; IDEC-C2B8; IDEC-C2B8 Monoclonal Antibody; Mabthera; MOAB IDEC-C2B8; Rituxan; Aldesleukin; IL-2; Interleukin II; Proleukin; Recombinant Human Interleukin-2; Recombinant Interleukin-2; TCGF; Interleukin

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed CD20 B cell non-Hodgkin's lymphoma
• Karnofsky performance status scores of 70 or greater (ECOG performance status 0 to 2).
• Age greater than 18.
• Eligible patients will start treatment between D+30 and D+100 from end of prior therapy
• Patients have obtained a complete remission after induction chemotherapy or salvage chemotherapy who are not candidates for autologous stem cell transplantation or at least a partial remission after autologous transplantation (Stem cell collection, if indicated, should be collected prior to starting therapy)
• International Prognostic Index (IPI)* or Follicular Lymphoma IPI (FLIPI)of 3 or more
• Adequate organ function that has been determined within 2 weeks prior to the study entry, defined as:
• Absolute neutrophil count (ANC) >/=1000/mm3, platelets >/=100,000/mm3, and hemoglobin >/=8 g/dl.
• Serum bilirubin < 1.5 times ULN and serum albumin > 2.0 g/dl.
• If female, neither pregnant (negative pregnancy test) nor breast-feeding.
• If of child bearing potential (< one year post-menopausal), must agree to practice an effective method of avoiding pregnancy (including oral or implanted contraceptives, intrauterine device, condom, diaphragm with spermicidal, cervical cap, abstinence or sterile sex partner) from the time informed consent is signed.
• No other concurrent active malignancy requiring treatment.
• Able to render informed consent and to follow protocol requirements.

Exclusion Criteria

• CNS lymphoma
• Presence of any other medical complications which imply a survival of less than three months.
• Prior IL-2 therapy
• HIV or Viral Hepatitis
• Karnofsky performance score less than 70.
• Pregnancy or breast-feeding.
• Unable or unwilling to utilize contraception if of childbearing potential.
• Severe cardiovascular disease within 12 months including myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attach, pulmonary embolism, life threatening arrhythmias, or uncontrollable hypertension.
• Autoimmune disorders
• Concurrent immunosuppressive medications
• Concurrent systemic corticosteroids at doses greater than replacement levels
• Prior history of intolerance to rituximab

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sidney Kimmel Cancer Center at Thomas Jefferson University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Matthew Carabasi, MD

Role: PRINCIPAL_INVESTIGATOR

Thomas Jefferson University

Locations

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Countries

United States

Related Links

http://www.KimmelCancerCenter.org

Kimmel Cancer Center at Thomas Jefferson University, an NCI-Designated Cancer Center

Other Identifiers

2008-40

Identifier Type: OTHER

Identifier Source: secondary_id

JT 1375

Identifier Type: OTHER

Identifier Source: secondary_id

08S.461

Identifier Type: -

Identifier Source: org_study_id