24 Participants Needed

Rituximab + Immunotherapy for Follicular Lymphoma

Recruiting at 5 trial locations
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on anticancer therapies or investigational agents close to the start of the study. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug combination Rituximab and Avelumab for treating follicular lymphoma?

Rituximab has been shown to significantly improve outcomes for patients with follicular lymphoma, especially when used in combination with other treatments. It has been effective in achieving long-term remission and prolonging survival, and it works well with both chemotherapy and other targeted therapies.12345

What safety data exists for Rituximab and Utomilumab in treating follicular lymphoma?

In a study combining Utomilumab and Rituximab for follicular lymphoma, safety was evaluated, but specific safety outcomes were not detailed in the abstract. However, Rituximab alone has been well-tolerated in other studies, with no severe infusion reactions or infections reported.678910

How is the drug combination of Rituximab, Avelumab, PF04518600, and Utomilumab unique for treating follicular lymphoma?

This drug combination is unique because it combines Rituximab, a well-established monoclonal antibody targeting CD20 on B-cells, with Avelumab and Utomilumab, which are immunotherapies that enhance the body's immune response against cancer cells. This approach aims to improve treatment outcomes by leveraging both direct targeting of cancer cells and boosting the immune system, which is different from traditional chemotherapy-based treatments.12111213

What is the purpose of this trial?

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.

Research Team

CA

Caron A. Jacobson, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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.

Inclusion Criteria

I have follicular lymphoma, grade 1-3A, and have been treated with or without anti-CD-20 therapy.

Exclusion Criteria

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

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Rituximab, Utomilumab, Avelumab, and/or PF-04518600 in various combinations. Rituximab is administered for four weekly treatments in cycle 1, while other drugs are administered at specified intervals.

6 months
Visits every 2-4 weeks depending on drug regimen

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with assessments for progression-free survival and overall survival.

24 months
Contact every 3 months

Long-term follow-up

Participants are monitored for overall survival with less frequent contact.

3 years
Contact every 6 months

Treatment Details

Interventions

  • Avelumab
  • PF04518600
  • Rituximab
  • Utomilumab
Trial Overview 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.
Participant Groups
7Treatment groups
Experimental Treatment
Group I: Rituximab+Utomilumab+PF04518600-0.3mgExperimental 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, 0.3mg/kg
Group II: Rituximab+Utomilumab+Avelumab-3mgExperimental 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, 3mg/kg
Group III: Rituximab+Utomilumab+Avelumab-10mgExperimental 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, 10mg/kg
Group IV: Rituximab+PF04518600-0.3mg+Avelumab-3mgExperimental 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, 3mg/kg
Group V: Rituximab+PF04518600-0.3mg+Avelumab-10mgExperimental 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, 10mg/kg
Group VI: Rituximab+PF04518600-0.3mgExperimental Treatment2 Interventions
* Rituximab is administered intravenously per institutional standards for four weekly treatments for cycle 1 only * PF-04518600 is administered intravenously over 1 hour on day 1 and day 15, 0.3mg/kg
Group VII: PF04518600-0.3mgExperimental Treatment1 Intervention
-PF-04518600 is administered intravenously over 1 hour on day 1 and day 15, 0.3mg/kg

Avelumab is already approved in European Union, United States, Japan for the following indications:

🇪🇺
Approved in European Union as Bavencio for:
  • Merkel cell carcinoma
  • Renal cell carcinoma
  • Urothelial carcinoma
🇺🇸
Approved in United States as Bavencio for:
  • Merkel cell carcinoma
  • Renal cell carcinoma
  • Urothelial carcinoma
🇯🇵
Approved in Japan as Bavencio for:
  • Merkel cell carcinoma
  • Renal cell carcinoma
  • Urothelial carcinoma

Find a Clinic Near You

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials
1,128
Recruited
382,000+

Pfizer

Industry Sponsor

Trials
4,712
Recruited
50,980,000+
Known For
Vaccine Innovations
Top Products
Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni profile image

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Findings from Research

In a study of 60 patients with symptomatic or bulky follicular lymphoma, a combination of short-course chemoimmunotherapy (CHOP-R) followed by radioimmunotherapy (RIT) led to a significant increase in complete response (CR) rates, from 40% after CHOP-R to 82% after RIT, as assessed by imaging.
The study found that patients who did not achieve a complete metabolic response on PET imaging after CHOP-R had a higher risk of relapse, highlighting the importance of early PET assessment in predicting treatment outcomes.
Phase II trial of short-course CHOP-R followed by 90Y-ibritumomab tiuxetan and extended rituximab in previously untreated follicular lymphoma.Jacobs, SA., Swerdlow, SH., Kant, J., et al.[2016]
Rituximab, an anti-CD20 antibody, has significantly improved outcomes for patients with follicular lymphoma (FL), achieving long-term remission and prolonged failure-free survival, especially when used as a first-line treatment.
The drug not only works effectively on its own but also enhances the effectiveness of chemotherapy and other targeted therapies, making it a crucial component in the treatment of FL and a benchmark for developing new anti-CD20 monoclonal antibodies.
Rituximab: a benchmark in the development of chemotherapy-free treatment strategies for follicular lymphomas.Karmali, R., Kimby, E., Ghielmini, M., et al.[2020]
The use of the anti-CD20 monoclonal antibody rituximab has significantly improved survival rates in patients with follicular lymphoma (FL), especially when used in combination with chemotherapy for both induction and maintenance therapy.
Radioimmunotherapy (RIT) using radiolabelled anti-CD20 mAbs, such as (90)Y Ibritumomab tiuxetan and (131)I Tositumomab, has shown high response rates and durable remissions, particularly when used as consolidation therapy after initial treatment.
How have outcomes for patients with follicular lymphoma changed with the addition of monoclonal antibodies?Illidge, T., Chan, C.[2019]

References

Phase II trial of short-course CHOP-R followed by 90Y-ibritumomab tiuxetan and extended rituximab in previously untreated follicular lymphoma. [2016]
Rituximab: a benchmark in the development of chemotherapy-free treatment strategies for follicular lymphomas. [2020]
How have outcomes for patients with follicular lymphoma changed with the addition of monoclonal antibodies? [2019]
Biological therapy doublets: pairing rituximab with interferon, lenalidomide, and other biological agents in patients with follicular lymphoma. [2021]
Antibody Therapy Maintenance in Follicular Lymphoma. [2021]
Randomized trial of ofatumumab and bendamustine versus ofatumumab, bendamustine, and bortezomib in previously untreated patients with high-risk follicular lymphoma: CALGB 50904 (Alliance). [2020]
Efficacy and safety of new anti-CD20 monoclonal antibodies versus rituximab for induction therapy of CD20+ B-cell non-Hodgkin lymphomas: a systematic review and meta-analysis. [2023]
First-in-Human Study of Utomilumab, a 4-1BB/CD137 Agonist, in Combination with Rituximab in Patients with Follicular and Other CD20+ Non-Hodgkin Lymphomas. [2021]
Phase 2 multicentre study of single-agent ofatumumab in previously untreated follicular lymphoma: CALGB 50901 (Alliance). [2021]
The combination of ibrutinib and rituximab demonstrates activity in first-line follicular lymphoma. [2021]
Rituximab: as first-line maintenance therapy following rituximab-containing therapy for follicular lymphoma. [2021]
Evolving role of rituximab in the treatment of patients with non-Hodgkin's lymphoma. [2015]
Critical appraisal of rituximab in the maintenance treatment of advanced follicular lymphoma. [2022]
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