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Phase II Study of IL-2 and Rituximab Maintenance in High Risk B Cell Non-Hodgkin's Lymphoma

Phase 2
18 Years
Open (Enrolling)
High Risk Non-Hodgkin's Lymphoma

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Trial Information

Phase II Study of IL-2 and Rituximab Maintenance in High Risk B Cell Non-Hodgkin's Lymphoma

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.

Inclusion Criteria:

- Histologically confirmed CD20 B cell non-Hodgkin's lymphoma

- Karnofsky performance status scores of 70 or greater (ECOG performance status 0 to

- Age greater than 18.

- Eligible patients will start treatment between D+30 and D+100 from end of prior

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Potential efficacy of IL-2 with rituximab for NHL by evaluating time to progression

Outcome Time Frame:

six months after treatment

Safety Issue:


Principal Investigator

Matthew Carabasi, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Thomas Jefferson University


United States: Institutional Review Board

Study ID:




Start Date:

February 2009

Completion Date:

December 2014

Related Keywords:

  • High Risk Non-Hodgkin's Lymphoma
  • NHL
  • Non Hodgkin's Lymphoma
  • Lymphoma
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoma, B-Cell



Thomas Jefferson UniversityPhiladelphia, Pennsylvania  19107-6541