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

This study is currently recruiting participants.
Verified November 2013 by Thomas Jefferson University
Sponsor:
Information provided by (Responsible Party):
Thomas Jefferson University
ClinicalTrials.gov Identifier:
NCT00994643
First received: October 12, 2009
Last updated: November 6, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
High Risk Non-Hodgkin's Lymphoma
Biological: Rituximab
Biological: Interleukin-2
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of IL-2 and Rituximab Maintenance in High Risk B Cell Non-Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by Thomas Jefferson University:

Primary Outcome Measures:
  • Potential efficacy of IL-2 with rituximab for NHL by evaluating time to progression [ Time Frame: six months after treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 61
Study Start Date: February 2009
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • C2B8 Monoclonal Antibody
  • IDEC-C2B8
  • IDEC-C2B8 Monoclonal Antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
Biological: Interleukin-2
Given SC
Other Names:
  • Aldesleukin
  • IL-2
  • Interleukin II
  • Proleukin
  • Recombinant Human Interleukin-2
  • Recombinant Interleukin-2
  • TCGF
  • Interleukin

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00994643

Contacts
Contact: Matthew Carabasi, MD 215-955-8874
Contact: Clinical Research Management Office 215-955-1661

Locations
United States, Pennsylvania
Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Matthew Carabasi, MD    215-955-8874      
Contact: Clinical Research Management Office    215-955-1661      
Principal Investigator: Matthew Carabasi, MD         
Sub-Investigator: Neal Flomenberg, MD         
Sub-Investigator: Joanne Filicko-O'Hara, MD         
Sub-Investigator: John Wagner, MD         
Sub-Investigator: Margaret Kasner, MD         
Sub-Investigator: Lewis Rose, MD         
Sub-Investigator: Michael Ramirez, MD         
Sub-Investigator: Allison Zibelli, MD         
Sub-Investigator: Andrew Chapman, DO         
Sub-Investigator: Mark Weiss, MD         
Sub-Investigator: S. Onder Alpdogan, MD         
Sub-Investigator: Elena Gitelson, MD         
Sub-Investigator: Ubaldo Martinez Outschoorn, MD         
Sponsors and Collaborators
Thomas Jefferson University
Investigators
Principal Investigator: Matthew Carabasi, MD Thomas Jefferson University
  More Information

Additional Information:
No publications provided

Responsible Party: Thomas Jefferson University
ClinicalTrials.gov Identifier: NCT00994643     History of Changes
Other Study ID Numbers: 08S.461, 2008-40
Study First Received: October 12, 2009
Last Updated: November 6, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Thomas Jefferson University:
NHL
Non Hodgkin's Lymphoma
Lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies
Antibodies, Monoclonal
Rituximab
Aldesleukin
Interleukin-2
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on April 16, 2014