Follicular Lymphoma
Conditions
Keywords
Fullicular Lymphoma-Previously Untreated Low Tumor Burden, Mosunetuzumab
Brief summary
This is a multi-center, open-label, interventional clinical trial designed to evaluate the efficacy and safety of subcutaneous (SC) Mosunetuzumab as a first-line immunotherapy in patients with low tumor burden follicular lymphoma (LTB-FL), defined by the absence of GELF criteria.
Detailed description
Eligible patients will undergo screening and, upon signing an Informed Consent Form, will receive their first dose of SC Mosunetuzumab. Mosunetuzumab is administered via SC injection without the need for mandatory hospitalization. The first cycle lasts 21 days, followed by subsequent 21-day cycles. In Cycle 1, Mosunetuzumab is given on Day 1 (5 mg), Day 8 (45 mg), and Day 15 (45 mg). From Cycle 2 onward, a single 45 mg dose is administered on Day 1 of each cycle. Treatment continues for up to 8 cycles (approximately 6 months). Patients will be monitored for disease status according to standard clinical practice. After completing active treatment, they will enter a post-treatment follow-up phase. Premedication with dexamethasone (20 mg) is mandatory in Cycle 1 and optional in later cycles. Acetaminophen and diphenhydramine may also be administered. All patients will continue study treatment as per the Schedule of Activities or until premature discontinuation. After treatment discontinuation, disease status assessments will occur approximately every 3 months for up to 24 months. During post-treatment follow-up, PET-CT scans for disease evaluation will be performed every 6 months, as applicable. Patients not under active follow-up will be contacted annually to collect data on disease status and survival. Throughout the trial, the following data will be collected (as applicable): demographics and baseline characteristics (including sex, age, race, height, and weight), medical history, details of initial diagnosis and treatment history, concomitant medications, adverse events (AEs), serious adverse events (SAEs), disease response, and survival status.
Interventions
DRUGMosunetuzumab is a bispecific monoclonal antibody targeting CD20 on B cells and CD3 on T cells, redirecting T cells to eliminate malignant B cells.
In this study, Mosunetuzumab will be administered subcutaneously over 8 treatment cycles: 5 mg on Day 1 of Cycle 1, followed by 45 mg in all subsequent cycles.
Sponsors
Tel-Aviv Sourasky Medical Center
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a Phase 2, single-arm, open-label study evaluating the efficacy and safety of subcutaneous Mosunetuzumab in patients with low-tumor-burden follicular lymphoma. All participants will receive the same intervention product without randomization.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* at least 18 years old * Histologically confirmed classic FL (cFL) (according to WHO-HEAM4R classification) * Low tumor burden by GELF criteria * No prior therapy except surgery or radiotherapy for disease that was previously localized * Ann Arbor Stage III or IV disease * Bi-dimensionally measurable FDG-avid disease defined by at least one single node or tumor lesion \> 1.5 cm assessed by CT scan and/or clinical examination * Adequate hematologic function defined as follows without growth factors or blood product transfusion within 14 days of first dose of study drug administration: 1. Hemoglobin, without transfusion, 9 g/dL 2. ANC 1.0 109/L 3. Platelet count 75 109/L; * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 * Patient can understand and sign the Informed Consent Form (ICF), can communicate with the Investigator, can understand and comply with the requirements of the protocol
Exclusion criteria
* 1\. An active viral infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) defined by detectable viral DNA in the blood by PCR. Patients with HIV are eligible provided an undetectable viral load and a CD4 count \> 200 cell/mcl * 2\. Any of the following laboratory abnormalities: 1. Total Bilirubin or GGT or AST or ALT \> 3 X ULN. 2. Creatinine Clearance calculated by Cockcroft and Gault Formula \< 40 ml/min * Presence or history of CNS involvement by lymphoma * 4\. Prior history of malignancies other than Lymphoma (except for Basal Cell or Squamous Cell Carcinoma of the skin or carcinoma in situ of the cervix or breast) unless the subject has been free of the disease for ≥ 2 years * Contraindication to use Mosunetuzumabor known sensitivity or allergy * Pregnant or lactating females * 7\. Female patients of childbearing potential who cannot or do not wish to use an effective method of contraception, during the study treatment and for 3 months thereafter
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate-ORR Overall response rate (ORR) at the end of treatment (6 months) using the Lugano criteria | 6 months | ORR is defined as the proportion of patients who achieved Complete Response or Partial Response determined by Lugano 2014 criteria as assessed by investigators at 6 months after initiation of treatment and prior to the initiation of any subsequent anti-lymphoma therapy. Patients without post-baseline disease assessments will be considered non-responders. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival -PFS | up to 24 months after last treatment dose | PFS is defined as the time in months from the first dose of study drug to disease progression determined by Lugano 2014 criteria as assessed by investigator, or death from any cause. Surviving patients without disease progression will be censored at the time of the last adequate disease assessment. Surviving subjects without post-baseline disease assessment will be censored at the date of first dose of study drug. |
| Duration of response -DOR | up to 24 months after last treatment dose | DOR is defined for patients who achieved Complete Response (CR) or Partial Response (PR) ('responders'), as the time in months from initial CR/PR to disease progression determined by Lugano 2014 criteria as assessed by investigator, or death from any cause. Surviving responders without radiographic disease progression will be censored at the time of the last adequate disease assessment |
| Complete Response Rate - CRR - Lymphoma (FACT-Lym) subscale. | up to 24 months after last treatment dose | CRR is defined as the proportion of patients who achieved Complete Response, determined by Lugano 2014 criteria as assessed by the investigator. All responses of Complete Response after initiation of subsequent anti-lymphoma therapy will be excluded. Subjects without post-baseline disease assessments will be considered as not achieving Complete Response. |
| Duration of Complete Response -DOCR | up to 24 months after last treatment dose | DOCR is defined for patients who achieved Complete Response, as the time in months from initial CR/PR to disease progression determined by Lugano 2014 criteria as assessed by investigator, or death from any cause. Surviving responders without radiographic disease progression will be censored at the time of the last adequate disease assessment. |
| Time to Next Treatment -TTNT | up to 24 months after last treatment dose | TTNT is defined as the time from the date of the first dose of study drug to the start of new non-protocol-specified anti-lymphoma therapy or death due to disease progression. Surviving patients who were reported as not having started new non-protocol-specified anti-lymphoma therapy will be censored at the last known alive date to be free of non-protocol-specified anti-lymphoma therapy. Surviving patients without any post-baseline visit will be censored at the date of the first dose of study drug |
| Overall Survival -OS | up to 24 months after last treatment dose | OS is defined as the time in months from the first dose of study drug to death from any cause. Patients who are still alive at the end of the study or at the time of the analyses (12 and 24 months after the first dose of study drug) will be censored at the last known alive date |
| Statistical Analysis for Safety | from first dose through 90 days after administration of last dose | Incidence of adverse events (AEs) and abnormal laboratory test results - including all AEs, treatment-emergent AEs (TEAEs), Adverse drug reactions (ADRs), SAEs, AEs leading to discontinuation, and AEs leading to death. |
| Health related quality of life | whole treatment period- 6 months | Health-related quality of life will be assessed using the FACT-Lym (Functional Assessment of Cancer Therapy - Lymphoma) questionnaire. |
Countries
Israel
Contacts
CONTACTIrit Avivi, Prof
CONTACTIrit Segalovich, B.Sc
PRINCIPAL_INVESTIGATORIrit Avivi, Prof
Tel-Aviv Sourasky Medical Center
Outcome results
None listed