What side effects are associated with this type of intervention?

Rituximab, a CD20 monoclonal antibody, commonly causes infusion reactions, fever, chills, and infections. Utomilumab, a CD137 agonist, may lead to immune-related effects such as fatigue, fever, and autoimmune reactions. Avelumab, a PD-L1 inhibitor, can result in immune-mediated side effects including pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions. General side effects for these treatments include fatigue and gastrointestinal disturbances.

What prior FDA approvals exist?

Rituximab, a CD20 monoclonal antibody, has been FDA-approved for the treatment of Follicular Lymphoma and is commonly used in combination with chemotherapy regimens. Avelumab, a PD-L1 inhibitor, is approved for other cancers and is being explored for its potential in treating lymphomas. Utomilumab, a CD137 agonist, is still under investigation and has not yet received FDA approval for Follicular Lymphoma. The combination of these immunotherapeutic agents is a promising area of research.

What other types of research exist?

Promising novel alternatives for Follicular Lymphoma treatment in 2024 include: 1) Obinutuzumab (a glycoengineered type II anti-CD20 monoclonal antibody), 2) Tazemetostat (an EZH2 inhibitor), 3) CAR T-cell therapies such as Axicabtagene Ciloleucel and Tisagenlecleucel, and 4) Bispecific T-cell engagers (BiTEs) like Mosunetuzumab.

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Monoclonal Antibodies

Rituximab + Immunotherapy for Follicular Lymphoma

Phase 1

Waitlist Available

Led By Caron A. Jacobson, MD

Research Sponsored by Dana-Farber Cancer Institute

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Must not have

Patients currently receiving anticancer therapies or who have received anticancer therapies within 28 days of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, etc.), or 56 days for radioimmunotherapy. Steroids for symptom palliation are allowed, but must be either discontinued or on stable doses of < 10mg daily of prednisone (or the equivalent) at the time of initiation of protocol therapy, Patients may not be receiving any other investigational agents, or have received investigational agents within 4 weeks (or 3 half-lives, whichever is longer) of beginning treatment, History of severe allergic or anaphylactic reactions to monoclonal antibody therapy unless in consultation with an allergy specialist they are deemed eligible for retreatment with desensitization, Patients who have previously received therapy with any drug that works by a similar mechanism of action as any drug being tested in a given cohort will be excluded from that cohort but will be allowed to enroll in other open cohorts, Patients who have undergone prior allogeneic stem cell transplantation, Patients with a history of or active autoimmune disease (except controlled asthma, Hashimoto thyroiditis, atopic dermatitis, and/or vitiligo), or requiring systemic corticosteroids at a dose of 10mg prednisone equivalent daily. Patients with a history of autoimmune disease who never required corticosteroids and with no evidence of disease activity, and in whom the risk of reactivation is felt not to be serious, may be enrolled after discussion with the overall study chair. Exceptions to this are patients with a history of inflammatory bowel disease (ulcerative colitis and Crohn's disease). These patients are excluded regardless of whether their disease is active or inactive, Patients with active pneumonitis or colitis, or patients with chronic liver disease and/or cirrhosis, Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study, Patients with known leptomeningeal or brain metastases. Imaging or spinal fluid analysis to exclude CNS involvement is not required, unless there is clinical suspicion by the treating investigator, Patients with known HIV infection or hepatitis B or C infection. Testing for HIV is optional. Testing for hepatitis B and C is mandatory. Patients with hepatitis B core Ab positivity but negative surface antigen and negative viral load may be enrolled if they can be treated with a prophylactic agent (eg, entecavir); patients with hepatitis C seropositivity who have undergone successful treatment with negative viral load can also be enrolled, Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment), Prior history of another malignancy (except for non-melanoma skin cancer or in situ cervical or breast cancer) unless disease free for at least three years. Patients with prostate cancer are allowed if PSA is less than 1, Patients should not have received immunization with attenuated live vaccine within one week of study entry or during study period, Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. Women of child bearing potential (WOCBP) or male study participants of reproductive potential must agree to use double barrier birth control method of contraception during the course of the study treatment period and for 3 months after completing study treatment. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who are not postmenopausal (no menses) for at least 12 consecutive months. WOCBP must have a negative urine or serum pregnancy test within 14 days prior to administration of treatment, History of noncompliance to medical regimens, Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: New York Heart Association Class III or IV cardiac disease, including pre-existing clinically significant arrhythmia, congestive heart failure, or cardiomyopathy, Patients with a history of previous anthracycline treatment and are at risk of cardiac failure (New York Heart Association Class II or above) are excluded from cohorts A2, A3, and B2 (cohorts that include PF04518600), Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease, Patients with any one of the following currently on or in the previous 6 months will be excluded from cohorts A2, A3, and B2 (any cohort that includes treatment with PF04518600) myocardial infarction, congenital long QT syndrome, torsade's de points, left anterior hemiblock (bifascicular block), unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism or other clinically significant episode of thrombo-embolic disease*. Ongoing cardiac dysrhythmias of NCI CTCAE grade > 2, atrial fibrillation of any grade, or QTcF interval >470msec at screening (except in case of right bundle branch block, these cases must be discussed with the principal investigator). *Cases must be discussed in detail with the principal investigator to judge eligibility. Anticoagulation (heparin only, no vitamin K antagonists or factor Xa inhibitors will be allowed if indicated, Other uncontrolled intercurrent illness that would limit adherence to study requirements

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of three drugs to treat follicular lymphoma. It aims to find out if this mix is safe and effective. Rituximab targets cancer cells, while Utomilumab and Avelumab help the immune system fight the cancer. Epratuzumab is another drug being tested for its effectiveness in treating follicular lymphoma.

Who is the study for?

This trial is for adults over 18 with follicular lymphoma that's relapsed after treatment or hasn't been treated yet, except those with severe allergies to monoclonal antibodies, autoimmune diseases, active infections, other cancers within the last three years (some exceptions apply), and certain heart conditions. Participants need functioning major organs and can't be pregnant or breastfeeding.

What is being tested?

The study tests combinations of Rituximab with new drugs Utomilumab and Avelumab as potential treatments for follicular lymphoma. It aims to find out how well these drug combos work together in patients who have had previous treatments or are newly diagnosed.

What are the potential side effects?

Possible side effects include allergic reactions to the drugs, immune system complications potentially affecting various organs, fatigue, infusion-related reactions like fever or chills, and increased risk of infections due to a weakened immune response.

Eligibility Criteria

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

Complete response rate

Objective response rate

Partial Response Rate

+5 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Group I: Rituximab+Utomilumab+PF04518600Experimental Treatment3 Interventions

* Rituximab is administered intravenously per institutional standards for four weekly treatments for cycle 1 only * Utomilumab is administered intravenously over 1 hour once every 4 weeks * PF-04518600 is administered intravenously over 1 hour on day 1 and day 15

Group II: Rituximab+Avelumab+PF04518600Experimental Treatment3 Interventions

* Rituximab is administered intravenously per institutional standards for four weekly treatments for cycle 1 only * Avelumab is administered intravenously over 1 hour once every 2 weeks * PF-04518600 is administered intravenously over 1 hour on day 1 and day 15

Group III: Rituximab +Utomilumab+AvelumabExperimental Treatment3 Interventions

* Rituximab is administered intravenously per institutional standards for four weekly treatments for cycle 1 only * Utomilumab is administered intravenously over 1 hour once every 4 weeks * Avelumab is administered intravenously over 1 hour once every 2 weeks

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Utomilumab

2017

Completed Phase 2

~30

Rituximab

1999

Completed Phase 4

~2990

Avelumab

2017

Completed Phase 2

~2440

0 / 1Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Follicular Lymphoma include Rituximab, Utomilumab, and Avelumab. Rituximab is a CD20 monoclonal antibody that targets and destroys B-cells by binding to the CD20 protein on their surface. Utomilumab is a CD137 agonist that boosts the immune response by activating T-cells. Avelumab is a PD-L1 inhibitor that prevents tumor cells from evading the immune system by blocking the interaction between PD-1 on T-cells and PD-L1 on tumor cells. These treatments are significant for Follicular Lymphoma patients as they enhance the immune system's ability to target and eliminate cancerous B-cells, potentially improving treatment efficacy and patient outcomes.

Current approaches to the treatment of non-Hodgkin's lymphoma.