High Risk Non-Hodgkin's Lymphoma
Conditions
Keywords
NHL, Non Hodgkin's Lymphoma, Lymphoma
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.
Interventions
BIOLOGICALRituximab
Given IV
BIOLOGICALInterleukin-2
Given SC
Sponsors
Sidney Kimmel Cancer Center at Thomas Jefferson University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assess the Efficacy of Combination Immunotherapy With Rituximab and Interleukin-2 in Patients With Non-Hodgkin's Lymphoma | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Rituximab: Given IV
Interleukin-2: Given SC | 11 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Treatment (Interleukin Therapy, Monoclonal Antibody) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Age, Continuous | 59.3 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 11 / 11 |
| serious Total, serious adverse events | 5 / 11 |
Outcome results
Primary
Assess the Efficacy of Combination Immunotherapy With Rituximab and Interleukin-2 in Patients With Non-Hodgkin's Lymphoma
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.
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Interleukin Therapy, Monoclonal Antibody) | Assess the Efficacy of Combination Immunotherapy With Rituximab and Interleukin-2 in Patients With Non-Hodgkin's Lymphoma | 6 Participants |