High Risk Non-Hodgkin's LymphomaPhase 2NCT00994643
Safety and Efficacy Study of Immunotherapy With Rituximab and Interleukin-2 in Patients With Non-Hodgkin's Lymphoma
A Phase 2 study testing Rituximab and Interleukin-2 in people with High Risk Non-Hodgkin's Lymphoma, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- High Risk Non-Hodgkin's Lymphoma
- What is being tested?
- Rituximab and Interleukin-2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Feb 2009to 25 Jun 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
About this study
Official title: 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.
Read the 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
- Being tested
- Rituximab, Interleukin-2
- Keywords
- NHL, Non Hodgkin's Lymphoma, Lymphoma
- Medical subject headings
- Lymphoma, Non-Hodgkin, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabBiological
Also called C2B8 Monoclonal Antibody, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, Mabthera
Given IV
Interleukin-2Biological
Also called Aldesleukin, IL-2, Interleukin II, Proleukin
Given SC
| Study group | Role | What they receive |
|---|---|---|
| Treatment (Interleukin Therapy, Monoclonal Antibody) | Experimental | 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. Receives: Biological: Rituximab; Biological: Interleukin-2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2009 (estimated)
- Study start5 Feb 2009
- Primary completion25 Jun 2014
- Study completion25 Jun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for High Risk Non-Hodgkin's LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Matthew Carabasi, MD, Principal investigator, Thomas Jefferson University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00994643
- Sponsor's protocol ID
- 08S.461
- Other IDs
- 2008-40, JT 1375
- Status last verified
- Apr 2025
- First submitted
- 12 Oct 2009
- Last updated
- 30 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of IL-2 and Rituximab Maintenance in High Risk B Cell Non-Hodgkin's Lymphoma
- ClinicalTrials.gov ID
- NCT00994643
- Acronym / sponsor ID
- 08S.461
- Conditions
- High Risk Non-Hodgkin's Lymphoma
- Keywords
- NHL, Non Hodgkin's Lymphoma, Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson UniversityUniversity, hospital or other
- Study start
- 5 Feb 2009 (actual)
- Primary completion
- 25 Jun 2014 (actual)
- Study completion
- 25 Jun 2015 (actual)
- First posted
- 14 Oct 2009 (estimated)
- Results
- Posted 6 Oct 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (Interleukin Therapy, Monoclonal Antibody) | Experimental | Biological: Rituximab, Biological: Interleukin-2Patients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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)
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RituximabAlso: C2B8 Monoclonal Antibody, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabtheraGiven IV | Biological | Treatment (Interleukin Therapy, Monoclonal Antibody) |
| Interleukin-2Also: Aldesleukin, IL-2, Interleukin II, ProleukinGiven SC | Biological | Treatment (Interleukin Therapy, Monoclonal Antibody) |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Kimmel Cancer Center at Thomas Jefferson University, an NCI-Designated Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthew Carabasi, MD principal investigator
Thomas Jefferson University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rituximab and Interleukin-2 in people with High Risk Non-Hodgkin's Lymphoma, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Oct 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assess the Efficacy of Combination Immunotherapy With Rituximab and Interleukin-2 in Patients With Non-Hodgkin's Lymphoma (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2025; AzTrials last refreshed its copy on 7 Nov 2026.