Phase II Multicenter Clinical Trial: Mosunetuzumab for Early Relapse of Follicular Lymphoma in the Nordic Countries

EU CT NO: 2022-500100-21-01

In this clinical trial adult patients diagnosed with follicular lymphoma and relapse or progression of disease within 24 months of starting first line treatment will be treated with mosunetuzumab. This is a bispecific antibody, a new type of immunotherapy that redirects the bodies own immune cells (T-cells) to attack and kill the lymphoma cells. The main question the trial aims to answer is if mosunetuzumab works better than standard treatments in this sub-group of patients. Patients will receive mosunetuzumab as injections in the abdominal subcutaneous fat once a week for the three first doses, then every third week 7 times. If all signs of disease are gone as evaluated by PET-CT images, the treatment is stopped. If signs of disease remain on PET-CT images, the patients can receive treatment every third week for up to a total of one year. After the end of treatment, patients are followed two years in the trial for signs of progression or relapse.

2023-09-11

2027-06-01

2028-08-01

Recruiting

Early phase I

80

Inclusion Criteria: 1. Written informed consent according to ICH-GCP guidelines. 2. Age ≥ 18 years. 3. Follicular lymphoma grade 1-3a with a current relapse or progression within 24 months of starting 1st line treatment or refractory to 1st line treatment (POD24), more specifically: 1. Documented current relapse or progression of FL within 24 months of starting first line treatment containing a monospecific anti-CD20 antibody (such as rituximab or obinutuzumab with or without chemotherapy, small molecular inhibitors or immunomodulating agents such as lenalidomide). 2. Current lack of response/refractoriness to first line treatment, i.e., no objective response or documented progression within 6 months following at least four cycles of monotherapy with a monospecific anti-CD20 antibody (such as rituximab 375mg/m2 iv or 1400 mg SC or equal) or following at least three cycles of a monospecific anti CD20 antibody combined with chemotherapy, small molecular inhibitors or immunomodulating agents such as lenalidomide. 3. Received one prior treatment line of systemic therapy. 4. Patients may have had a period of watch and wait before the initiation of first line treatment. 5. Patients may have received localized radiotherapy previously. 4. At least one two-dimensionally measurable lesion with a longest diameter \>15mm. 5. WHO performance status 0-2. Patients with reduced WHO performance status (\> 2) can be considered if reduction in performance is caused by the lymphoma as determined by the investigator. Exclusion Criteria: 1. Received 2 or more previous treatment lines. 2. Grade 3b FL. 3. CD20-negative lymphoma. 4. CNS involvement (current or previous). 5. Impaired bone marrow function (neutrophils \< 1.0 x 109/L or platelets \< 50 x 109/L) unless due to lymphoma involvement. 6. Severe cardiac disease: impaired cardiac function (NYHA class III or IV), myocardial infarction within the last 6 months, unstable arrythmias and/or unstable angina pectoris. 7. Impaired liver function not caused by lymphoma, defined as serum total bilirubin ≥ 1.5 x ULN (unless elevated due to Gilbert's syndrome) or serum ALT and AST \> 3 x ULN. 8. Impaired renal function not caused by lymphoma, defined as calculated creatinine clearance ≤ 40 ml/minute. 9. Other major organ dysfunction not caused by lymphoma. 10. Known history of drug induced liver injury, chronic active hepatitis C (HCV), chronic active hepatitis B (HBV), alcoholic liver disease, primary biliary cirrhosis, on-going extra-hepatic obstruction caused by cholelithiasis, cirrhosis of the liver or portal hypertension. 11. Active severe infection. 12. Hepatitis B (HBV) or hepatitis C (HCV) infection: Subjects with a previous hepatitis B infection will be eligible if they are negative for HBV-DNA; these subjects must be given prophylactic antiviral therapy. Subjects with a previous HCV infection will be eligible if they are negative for HCV-RNA. 13. Known or suspected chronic active Epstein-Barr virus (EBV) infection. 14. Received systemic immunosuppressive medications (including but not limited to cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within two weeks prior to the first dose of mosunetuzumab. 15. Administration of live vaccines within four weeks of the first dose of mosunetuzumab or anticipation that live vaccine will be required during the study. 16. History of severe allergic or anaphylactic reactions to chimeric, human, or humanized antibodies, or fusion proteins. 17. Known or suspected hemophagocytic syndrome. 18. Prior allogeneic hematopoietic stem cell transplant. 19. Other current severe medical problems or expected survival of less than approximately five years for non-lymphoma reasons. 20. Current or previous other malignancy within three years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other non-invasive or indolent malignancy without sponsor approval. 21. Psychiatric disorder or dementia which make the patient unable to give an informed consent and/or adhere to the schedule. 22. Pregnancy or breast-feeding. 23. HIV positivity: Subjects that are on HIV-treatment with undetectable HIV-RNA and CD4-counts above 200 will be eligible. 24. Women of reproductive potential not agreeing to use an acceptable method of birth control during treatment and for three months after completion of treatment.

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2023-11-01