Tazemetostat and Mosunetuzumab in Untreated Follicular Lymphoma
Status and phase
Conditions
Treatments
Details and patient eligibility
About
The goal of this study is to learn about the safety and effectiveness of the combination of tazemetostat pills in combination with mosunetuzumab injections for people with follicular lymphoma who haven't received treatment before. The investigators hypothesize that tazemetostat with mosunetuzumab has the potential to increase the efficacy of the product without compromising the safety.
Tazemetostat is a drug that inhibits EZH2, an enzyme known to drive the development of B-cell lymphomas, and inhibiting it appears to have many effects that slow down lymphoma growth and enhance the immune system's ability to fight it. Tazemetostat is FDA-approved in previously treated follicular lymphoma and currently undergoing study in other lymphomas.
Mosunetuzumab is a bispecific antibody therapy that is a therapeutic strategy that uses the immune system to fight lymphoma, called immunotherapy. Bispecific antibodies have two ends: one attaches to T cells in the immune system and the other attaches to lymphoma cells, helping guide our immune system to attack the cancer. Mosunetuzumab has been studied in follicular lymphoma that has previously been treated, with positive results. Mosunetuzumab is approved by the FDA to be given intravenously (directly into a vein) but is not yet approved by the FDA is not yet approved as an injection under the skin, which is how it is given in this study. They have not yet been studied in combination.
Full description
This is a phase II, open-label study. Fifty patients with previously untreated follicular lymphoma will be enrolled and treated with standard dosing of subcutaneous mosunetuzumab, and with oral tazemetostat by mouth twice daily at standard dosing (800 mg twice daily) beginning at the same time as mosunetuzumab initiation. Mosunetuzumab and tazemetostat will be given in 28-day cycles for up to 12 cycles. Response assessments by PET/CT will occur at 12 weeks post-mosunetuzumab and again at 30 and 48 weeks for those with an ongoing response to treatment. Treatment with steroids, tocilizumab, growth factors, tumor lysis prophylaxis, and antibiotics may be used as per standard of care at our institution. Dose modifications are permitted for toxicity. There will be a follow-up visit after 2 years from starting the study.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
- Ability to comply with the study protocol
- Willing to use highly effective contraception, if of childbearing potential
- Diagnosed with follicular lymphoma (FL; Grades 1-3a)
- Received no prior systemic lymphoma therapy (local radiotherapy is not considered systemic therapy)
Exclusion criteria
- Inability to take oral medication OR have malabsorption syndrome or any other uncontrolled gastrointestinal condition (eg, nausea, diarrhea, vomiting) that might impair the bioavailability of tazemetostat
- Grade 3b FL
- History of transformation of indolent disease to diffuse large B cell lymphoma
- Any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or myeloproliferative neoplasm (MPN)
- Any prior history of T cell lymphoblastic lymphoma (T-LBL)/ T cell lymphoblastic leukemia (T-ALL)
- Active or history of central nervous system lymphoma or leptomeningeal infiltration
- Prior standard or investigational systemic anti cancer therapy for lymphoma. Patients who have received prior XRT will not be excluded
- History of solid organ transplantation
- History of severe allergic or anaphylactic reaction to humanized, chimeric or murine monoclonal antibodies (MAbs)
- Known or suspected chronic active Epstein-Barr virus (EBV) infection
- Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
- Clinically significant history of liver disease, including viral or other hepatitis, or cirrhosis
- Active Hepatitis B or Hepatitis C infection
- HIV positive with CD4 count <200 and not currently taking antiretroviral therapy
- History of progressive multifocal leukoencephalopathy (PML)
- Active autoimmune disease requiring treatment
- History of autoimmune disease, including, but not limited to: myocarditis, pneumonitis, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
- Prior allogeneic stem cell transplant (SCT)
- Significant cardiovascular disease (e.g., New York Heart Association Class III or IV cardiac disease, myocardial infarction within the previous 6 months, unstable arrhythmia, or unstable angina) or significant pulmonary disease (such as obstructive pulmonary disease or history of bronchospasm)
- Major surgery other than for diagnosis within 28 days prior to Day 1 of Cycle 1 Day 1 or anticipation of a major surgical procedure during the course of the study
- Active central nervous system disease or underlying neurologic disease such as stroke or intracranial hemorrhage within 3 months prior to enrollment, history of seizure disorder, or history of neurogenerative disease
- History of pneumonitis or interstitial lung disease
- Pregnant or breastfeeding or intending to become pregnant during the study
Trial design
Primary purpose
Allocation
Interventional model
Masking
50 participants in 1 patient group
Trial contacts and locations
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Central trial contact
Brittany Hobbie; Tejasvi Kaur Sahni
Data sourced from clinicaltrials.gov
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