Mosunetuzumab in Patients With Newly Diagnosed Extranodal Marginal Zone Lymphoma
- Conditions
- Extranodal Marginal Zone Lymphoma
- Registration Number
- NCT06569680
- Lead Sponsor
- Izidore Lossos, MD
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Not yet recruiting
- Sex
- All
- Target Recruitment
- 35
Inclusion Criteria:<br><br> 1. Men and women aged 18 years or older at the time of signing informed consent.<br><br> 2. Able and willing to sign the informed consent form (ICF).<br><br> 3. Ability to comply with the trial protocol.<br><br> 4. Histologically confirmed EMZL presenting with stage I-IV disease.<br><br> 5. Previously untreated participants.<br><br> 1. Participants with H. pylori-positive gastric EMZL who received an initial<br> treatment with currently accepted antibiotics may be considered eligible if,<br> after antibiotic regimen, participant has histologically confirmed MZL.<br><br> 2. Participants who were previously treated with localized therapy (eg, radiation<br> or surgery) and never received systemic therapy and present with recurrent<br> disease are eligible upon histological confirmation of MZL.<br><br> 6. Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy<br> (defined as the presence of =1 lesion that measures >1.5 cm in the longest diameter<br> (LDi) and =1.0 cm in the longest perpendicular diameter as assessed by CT or MRI,<br> especially in extranodal sites, per response criteria for lymphomas (Cheson, et al.,<br> 2014). Imaging must be conducted within 6 weeks prior to the start of therapy.<br><br> 1. Participants with skin EMZL who do not meet the radiographically measurable<br> disease criteria described herein are eligible for participation provided that<br> skin lesion measures =1.5 cm in diameter by tape measure and is documented by<br> photo or there are multiple skin lesions measuring >1 cm in diameter on the<br> body and at least one of them is histologically confirmed as EMZL.<br><br> 2. Participants with gastric EMZL histologically confirmed and need therapy but do<br> not have measurable disease and in which response to treatment can be assessed<br> by multiple random gastric biopsies per Groupe d'Etude des Lymphomes de l'Adult<br> (GELA) criteria (Ruskoné Fourmestraux, et al., 2011).<br><br> 3. Participants with conjunctival EMZL who do not meet the radiographically<br> measurable disease criteria described herein are eligible for participation<br> provided that conjunctival lesion measures =1 cm in diameter by tape measure<br> and is documented by photo or there are multiple conjunctival lesions measuring<br> together >1.5 cm. At least one of the lesions needs be histologically confirmed<br> as EMZL.<br><br> 7. Participants must be willing to provide tissue biopsy from the most recent available<br> archival tissue or undergo an incisional or excisional lymph node or tissue biopsy.<br> If biopsy can be reviewed to confirm the diagnosis but there is no extra tissue for<br> exploratory studies, such participants can still be enrolled in this trial.<br><br> 8. Participant should have at least one of the following criteria for treatment<br> initiation:<br><br> - Threatened extranodal organ function<br><br> - Involvement of =3 nodal sites, each with diameter of =3 cm<br><br> - Any nodal or extranodal tumor mass with a diameter of =5 cm<br><br> - B symptoms (fever =38 degrees Celsius of unclear etiology, night sweats, weight<br> loss >10% within the prior 6 months) or other symptoms attributed to disease or<br> specific organ involvement associated with the relapse.<br><br> - Risk of local compressive symptoms that may result in organ compromise<br><br> - Splenomegaly or splenic lesion without splenomegaly<br><br> - Leukopenia attributed to MZL (leukocytes <1000/mm3)<br><br> - Leukemia (>5,000 lymphoma cells/mm3)<br><br> - Requirement for transfusion or growth factor support attributed to lymphoma<br><br> - Involvement of 2 or more extranodal sites, with tumor/lesion in each extranodal<br> site =1 cm<br><br> 9. Life expectancy >3 months.<br><br> 10. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.<br><br> 11. Adequate hematologic, hepatic, and renal function tested within 6 weeks prior to the<br> start of therapy (values must not be achieved with growth factors):<br><br> - Absolute neutrophil count (ANC) =1.0 × 10^9/L.<br><br> - Hemoglobin =8.0 g/dL.<br><br> - Platelet count = 75 × 10^9/L.<br><br> - Total bilirubin =1.5 × upper limit normal (ULN). Participants with documented<br> history of Gilbert's syndrome and in whom total bilirubin elevations are<br> accompanied by elevated indirect bilirubin are eligible.<br><br> - Alanine transaminase (ALT)/aspartate aminotransferase (AST) =3.0 × ULN or =5 ×<br> ULN in the presence of liver involvement by lymphoma.<br><br> - Creatinine within normal institutional limits, or<br><br> - calculated creatinine clearance =30 mL/min/1.73 m2 using the Modification<br> of Diet in Renal Disease formula<br><br> - calculated creatinine clearance =35 mL/min by the Cockcroft-Gault Equation<br> (Cockcroft, 1976)<br><br> - estimated glomerular filtration rate (eGFR) =30 mL/min/1.73 m2 using the<br> Modification of Diet in Renal Disease formula for participants with<br> creatinine levels above institutional normal (unless due to lymphoma)<br><br> 12. Willingness to avoid pregnancy during the trial and for at least 90 days after the<br> last dose of the trial intervention.<br><br>Exclusion Criteria:<br><br> 1. Evidence of diffuse large B cell lymphoma (DLBCL) transformation. Participants with<br> presumptive evidence of transformation based on clinical assessment of factors such<br> as, but not limited to, increasing lactate dehydrogenase, rapidly worsening disease,<br> or frequent B-symptoms, must be ruled out for a transformation to a more aggressive<br> disease, such as DLBCL.<br><br> 2. History of central nervous system lymphoma (either primary or metastatic) or<br> leptomeningeal disease. Participants with Dural MZL are eligible.<br><br> 3. Patients that need immediate cytoreduction.<br><br> 4. Concurrent or previous anticancer therapy (eg, chemotherapy, radiation therapy,<br> immunotherapy, biologic therapy, hormonal therapy, investigational therapy, or tumor<br> embolization).<br><br> 5. Treatment with systemic immunosuppressive medications, including, but not limited<br> to, prednisone (>20 mg), azathioprine, methotrexate, thalidomide, and anti-tumor<br> necrosis factor agents within 2 weeks prior to Day 1 of Cycle 1.<br><br> 1. Steroids that are used for treatment of allergy or other underlying condition<br> are permittable, but not steroids started to treat lymphoma. Participants<br> receiving corticosteroids must be at a dose level =20 mg/day within 7 days of<br> the trial intervention administration.<br><br> 2. The use of inhaled corticosteroids is permitted<br><br> 3. The use of mineralocorticoids for management of orthostatic hypotension is<br> permitted<br><br> 4. Single dose of dexamethasone for nausea or B symptoms is permitted<br><br> 5. Antibiotic treatment of H. pylori-positive gastric EMZL<br><br> 6. Allogeneic stem cell transplant, or autologous stem cell transplant or Chimeric<br> antigen receptor T-cell therapy for any indication<br><br> 7. Active graft versus host disease.<br><br> 8. Inadequate recovery from toxicity and/or complications from a major surgery before<br> starting therapy.<br><br> 9. Current or previous other malignancy within 3 years of trial entry, except cured<br>
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Complete Response (CR) Rate
- Secondary Outcome Measures
Name Time Method Overall Response Rate (ORR);Partial Response (PR) Rate;Number of Participants Experiencing treatment-related adverse events;Number of Participants Experiencing Cytokine Release Syndrome Adverse Events;Progression-Free Survival (PFS);Time to Response (TTR);Duration of Response (DOR);Overall Survival (OS)