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

April 3, 2018 updated by: Sidney Kimmel Cancer Center at Thomas Jefferson University

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

11

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Biological: Rituximab
Given IV
Other Names:
  • Rituxan
  • Mabthera
  • C2B8 Monoclonal Antibody
  • IDEC-C2B8
  • IDEC-C2B8 Monoclonal Antibody
  • MOAB IDEC-C2B8
Biological: Interleukin-2
Given SC
Other Names:
  • Proleukin
  • Aldesleukin
  • IL-2
  • Recombinant Human Interleukin-2
  • TCGF
  • Interleukin II
  • Interleukin
  • Recombinant Interleukin-2

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assess the Efficacy of Combination Immunotherapy With Rituximab and Interleukin-2 in Patients With Non-Hodgkin's Lymphoma
Time Frame: 1 year
Patients were enrolled based on having obtained complete remission or at least a partial remission. Efficacy was therefore determined by the number of patients that remained in remission following treatment.
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sidney Kimmel Cancer Center at Thomas Jefferson University

Investigators

  • Principal Investigator: Matthew Carabasi, MD, Thomas Jefferson University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 5, 2009

Primary Completion (Actual)

June 25, 2014

Study Completion (Actual)

June 25, 2015

Study Registration Dates

First Submitted

October 12, 2009

First Submitted That Met QC Criteria

October 13, 2009

First Posted (Estimate)

October 14, 2009

Study Record Updates

Last Update Posted (Actual)

May 4, 2018

Last Update Submitted That Met QC Criteria

April 3, 2018

Last Verified

April 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 08S.461
  • 2008-40 (Other Identifier: CCRRC)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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