A Phase II Trial of Tazemetostat Plus Mosunetuzumab in Untreated Follicular Lymphoma
New trial tests combination therapy for untreated follicular lymphoma
Plain English Summary
Tazemetostat and Mosunetuzumab in Untreated Follicular Lymphoma is a Phase 2 clinical trial sponsored by Weill Medical College of Cornell University studying Follicular Lymphoma. This trial is testing a combination of tazemetostat pills and mosunetuzumab injections for people with follicular lymphoma who have not received prior treatment. It is for adults aged 18 and older with histologically confirmed follicular lymphoma that shows on PET scans and meets specific size criteria. Participants will take tazemetostat pills twice daily and receive mosunetuzumab injections weekly for up to 12 cycles. Alternative treatments for newly diagnosed follicular lymphoma include chemotherapy, immunotherapy, or targeted therapies, depending on the specific situation. The trial aims to enroll 23 participants.
Official Summary
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.
Who Can Participate
Here is what you need to know about eligibility for this trial. You can join if you are 18 or older, have been diagnosed with follicular lymphoma that is visible on PET scans and meets size requirements, and have not had any prior systemic treatment for lymphoma. You cannot join if you have a more aggressive form of lymphoma (Grade 3b), a history of certain blood cancers, active or past CNS lymphoma, or significant uncontrolled gastrointestinal issues. Your blood counts, kidney, and liver function must be within certain limits to participate. You must be able to take oral medication and comply with the study protocol. This trial is studying Follicular Lymphoma, so participants generally need a confirmed diagnosis.
What They're Measuring
The primary outcome measures how many patients achieve a complete disappearance of their lymphoma after completing the treatment, indicating a successful response. The specific primary outcome measures are: Number of participants who achieve a complete response (CR) by completion of therapy, as determined by the Lugano Criteria (Estimated day 336). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.
About This Phase
This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.
Why This Trial Matters
This trial addresses a need for new treatment options for patients with newly diagnosed follicular lymphoma, aiming to improve treatment effectiveness by combining two different types of drugs. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Follicular Lymphoma, where improved treatment options are needed.
Investor Insight
This trial is investigating a novel combination therapy for follicular lymphoma, a common type of non-Hodgkin lymphoma, potentially offering a new treatment option and representing an investment in in Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.
Is This Trial Right for Me?
Ask your doctor about how tazemetostat and mosunetuzumab work, potential side effects, and if this trial is the best option for you compared to standard treatments. Participation involves regular clinic visits for medication, blood tests, scans, and monitoring for side effects. You will need to take tazemetostat pills daily at home and receive mosunetuzumab injections at the study site. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.
AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.
Study Design
- Study Type: INTERVENTIONAL
- Allocation: NA
- Model: SINGLE_GROUP
- Masking: NONE
- Enrollment: 23 participants
Interventions
- DRUG: Mosunetuzumab — Mosunetuzumab will be administered in weekly dose increments ("step-up dosing") during Cycle 1 and then on Day 1 of each cycle. Mosunetuzumab will be given in 28-day cycles for up to 12 cycles. Mosunetuzumab will be administered SC at the dose of 5 mg on Day 1, 45 mg on Day 8, and 45 mg on Day 15 in Cycle 1. Beginning with Cycle 2, it will be administered SC at the dose of 45 mg on Day 1. Each cycle lasts 4 weeks.
- DRUG: Tazemetostat Pill — Oral tazemetostat will be administered by mouth twice daily at standard dosing (800 mg twice daily) beginning at the same time as mosunetuzumab initiation until disease progression, unacceptable toxicity, or consent is withdrawn. Patients will remain on tazemetostat for up to twelve 28-day cycles from initiation of mosunetuzumab.
Primary Outcomes
- Number of participants who achieve a complete response (CR) by completion of therapy, as determined by the Lugano Criteria (Estimated day 336)
Secondary Outcomes
- Number of participants who experience cytokine release syndrome (CRS) (Day 0 to Day 28)
- Number of participants who experience Immune effector cell-associated neurotoxicity syndrome (ICANS) (Day 0 to Day 28)
- Median Progression-Free Survival (PFS) (For a maximum of approximately 10 years)
- Median Overall Survival (OS) (For a maximum of approximately 10 years)
- Objective Response Rate (ORR) at the time of therapy completion, as defined by Lugano Criteria (Estimated to be day 336)
Full Eligibility Criteria
Inclusion Criteria Patients must meet the following criteria for study entry: * Signed Informed Consent Form * Age \>=18 years at the time of signing Informed Consent Form * Ability to comply with the study protocol * Willing to follow lifestyle considerations as defined in Section 4.4 * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2 * Histologically documented FL: * Fluorodeoxyglucose avid lymphoma (i.e., positron emission tomography (PET) positive lymphoma) * At least 1 bi-dimensionally measurable nodal lesion (˃1.5 cm in its largest dimension by computed tomography (CT) scan), or at least 1 bi-dimensionally measurable extra-nodal lesion (˃1.0 cm in its largest dimension by CT scan) * Meet Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria or British National Lymphoma Investigation criteria to receive systemic therapy \- GELF criteria utilization (GELFc) or BNLI will be used to inform systemic therapy according to clinical applications of the GELF criteria. * Received no prior systemic lymphoma therapy (local radiotherapy is not considered systemic therapy) * Availability of a representative tumor specimen and the corresponding pathology report at the time of diagnosis for confirmation of the diagnosis of FL and for EZH2 mutation testing. * Adequate hematologic function defined as follows: * Hemoglobin\>= 8.0 g/dL * ANC \>= 1.0 x 109/L * Platelet count \>= 75 x 109/L * Adequate renal and hepatic function as defined as follows: * Measured or estimated creatinine clearance \>= 30 mL/min by institutional standard method * AST or ALT \<= 2.5 x the upper limit of normal (ULN) * Serum total bilirubin \<=1.5 x ULN (or \<= 3 x ULN for patients with Gilbert syndrome) Exclusion Criteria Patients who meet any of the following criteria will be excluded from study entry: * 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-LBL/T-ALL * Active or history of CNS lymphoma or leptomeningeal infiltration * Prior standard or investigational systemic anti-cancer therapy for lymphoma. Patients who have received prior XRT will not be excluded * Treatment with systemic immunosuppressive medications, including, but not limited to, prednisone (\> 20 mg), azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents within 2 weeks prior to Day 1 of Cycle 1 * The use of inhaled corticosteroids is permitted * The use of mineralocorticoids for management of orthostatic hypotension is permitted * Dexamethasone for nausea, B symptoms, or symptomatic or bulky disease is permitted with a maximum dose of 40 mg x5 days or equivalent * History of solid organ transplantation * Contraindication to tocilizumab * History of severe allergic or anaphylactic reaction to humanized, chimeric or murine monoclonal antibodies (MAbs) * Known hypersensitivity to biopharmaceuticals produced in CHO cells or any component of the mosunetuzumab or tazemetostat * Known active bacterial, viral, fungal, or other infection, or any major episode of infection requiring treatment with IV antibiotics within 4 weeks of Day 1 of Cycle 1 * 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, as determined by the principal investigator * Active Hepatitis B or Hepatitis C infection Note: Patients who are hepatitis B surface antigen (HBsAg) negative and hepatitis B core antibody (HBcAb) positive, must be negative for hepatitis B virus (HBV) polymerase chain reaction (PCR) to be eligible for study participation. Patients who are positive for hepatitis C virus (HCV) antibody must be negative for HCV by PCR to be eligible for study participation * HIV positive with CD4 count \<200 and not currently taking antiretroviral therapy * History of progressive multifocal leukoencephalopathy (PML) * Administration of a live, attenuated vaccine within 4 weeks before first dose of study treatment or anticipation that such a live attenuated vaccine will be required during the study * Patients must not receive live, attenuated vaccines (e.g., FluMist) while receiving study treatment or after the last dose until B-cell recovery to the normal ranges. * Inactivated influenza vaccination should be given during the influenza season only * Other malignancy that could affect compliance with the protocol or interpretation of results, with the exception of the following: * Any of the following maligna
Trial Locations
- Weill Cornell Medicine/NewYork-Presbyterian Hospital, New York, New York, United States
Frequently Asked Questions
What is clinical trial NCT05994235?
NCT05994235 is a Phase 2 INTERVENTIONAL study titled "Tazemetostat and Mosunetuzumab in Untreated Follicular Lymphoma." It is currently active, not recruiting and is sponsored by Weill Medical College of Cornell University. The trial targets enrollment of 23 participants.
What conditions does NCT05994235 study?
This trial investigates treatments for Follicular Lymphoma. The primary condition under study is Follicular Lymphoma.
What treatments are being tested in NCT05994235?
The interventions being studied include: Mosunetuzumab (DRUG), Tazemetostat Pill (DRUG). Mosunetuzumab will be administered in weekly dose increments ("step-up dosing") during Cycle 1 and then on Day 1 of each cycle. Mosunetuzumab will be given in 28-day cycles for up to 12 cycles. Mosunetuzumab will be administered SC at the dose of 5 mg on Day 1, 45 mg on Day 8, and 45 mg on Day 15 in Cycle 1. Beginning with Cycle 2, it will be administered SC at the dose of 45 mg on Day 1. Each cycle lasts 4 weeks.
What does Phase 2 mean for NCT05994235?
Phase 2 trials test whether the treatment works for the intended condition. They involve 100-300 patients and continue to evaluate safety while measuring effectiveness.
What is the current status of NCT05994235?
This trial is currently "Active, Not Recruiting." It started on 2023-11-01. The estimated completion date is 2033-10.
Who is sponsoring NCT05994235?
NCT05994235 is sponsored by Weill Medical College of Cornell University. The sponsor is responsible for funding, designing, and overseeing the clinical trial.
How many people can participate in NCT05994235?
The trial aims to enroll 23 participants. The trial status is active, not recruiting.
How is NCT05994235 designed?
This is a interventional study, uses na allocation, follows a single_group design, employs none masking.
What are the primary outcomes being measured in NCT05994235?
The primary outcome measures are: Number of participants who achieve a complete response (CR) by completion of therapy, as determined by the Lugano Criteria (Estimated day 336). These are the main endpoints researchers use to determine whether the treatment is effective.
Where is NCT05994235 being conducted?
This trial is being conducted at 1 site, including New York, New York (United States).
Where can I find official information about NCT05994235?
The official record for NCT05994235 is available on ClinicalTrials.gov at https://clinicaltrials.gov/study/NCT05994235. This government database provides the most up-to-date and detailed information about the trial.
What is NCT05994235 testing in simple terms?
This trial is testing a combination of tazemetostat pills and mosunetuzumab injections for people with follicular lymphoma who have not received prior treatment. It is for adults aged 18 and older with histologically confirmed follicular lymphoma that shows on PET scans and meets specific size criteria.
Why is this trial significant?
This trial addresses a need for new treatment options for patients with newly diagnosed follicular lymphoma, aiming to improve treatment effectiveness by combining two different types of drugs.
What are the potential risks of participating in NCT05994235?
Common side effects may include low blood cell counts (anemia, low white blood cells, low platelets), fatigue, nausea, and muscle pain. A serious potential risk is cytokine release syndrome (CRS), an inflammatory reaction that can cause fever, low blood pressure, and breathing problems. Another potential risk is immune effector cell-associated neurotoxicity syndrome (ICANS), which can cause confusion, seizures, or difficulty speaking. As with any clinical trial, participants are closely monitored and can withdraw at any time.
Should I consider participating in NCT05994235?
Ask your doctor about how tazemetostat and mosunetuzumab work, potential side effects, and if this trial is the best option for you compared to standard treatments. Participation involves regular clinic visits for medication, blood tests, scans, and monitoring for side effects. You will need to take tazemetostat pills daily at home and receive mosunetuzumab injections at the study site. Always discuss clinical trial participation with your healthcare provider to determine if it is appropriate for your specific situation.
What does NCT05994235 signal from an investment perspective?
This trial is investigating a novel combination therapy for follicular lymphoma, a common type of non-Hodgkin lymphoma, potentially offering a new treatment option and representing an investment in in This is a Phase 2 trial, which is focused on confirming efficacy before larger pivotal studies.
What happens if the treatment in this trial doesn't work?
Participants will take tazemetostat pills twice daily and receive mosunetuzumab injections weekly for up to 12 cycles. Participants in clinical trials always have the right to withdraw and pursue alternative treatments. The study team will help transition patients to other available options.
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This analysis is AI-generated and does not constitute medical advice. Always consult your healthcare provider before making decisions about clinical trial participation.