An Open-Label Study Evaluating the Efficacy and Safety of Mosunetuzumab in Combination with Polatuzumab Vedotin in Participants with Aggressive B-Cell Non Hodgkin's Lymphoma

JRCT ID: jRCT2011220013

Registered date:04/08/2022

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: CD20-positive B-cell non-Hodgkin's lymphoma
• Date of first enrollment: 30/09/2022
• Target sample size: 222
• Countries of recruitment: Argentina,Japan,Brazil,Japan,Canada,Japan,Israel,Japan,Korea,Japan,Mexico,Japan,New Zealand,Japan,Thailand,Japan,Turkey,Japan,Peru,Japan
• Study type: Interventional

Intervention(s)

mosunetuzumab: Participants will receive SC mosunetuzumab in a step-up dosing schedule on Day 1, 8, and 15 of Cycle 1, and on Day 1 of Cycle 2-8.
polatuzumab vedotin: Participants will receive IV polatuzumab vedotin every three weeks (Q3W) for 6 cycles (cycle length = 21 days).
tocilizumab: Participants will receive IV tocilizumab as needed to manage cytokine release syndrome (CRS) events.
rituximab: Participants will receive IV rituximab on Day 1 of each cycle for 8 cycles (cycle length = 14 days).
gemcitabine: Participants will receive IV gemcitabine on Day 1 of each cycle for 8 cycles (cycle length = 14 days).
oxaliplatin: Participants will receive IV oxaliplatin on Day 1 of each cycle for 8 cycles (cycle length = 14 days).

Outcome(s)

Primary Outcome

Efficacy
Lugano 2014 Response Criteria

Secondary Outcome

Safety, Efficacy, Confirmatory, Exploratory, Phamacokinetics, Phamacodynamics, Phamacogenomics, Other
NCI CTCAE v5.0, ASTCT Grading system

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

-Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
-CD20+ aggressive lymphoma as determined by the local hemopathology laboratory from the following diagnoses by 2016 World Health Organization classification of lymphoid neoplasms: DLBCL, not otherwise specified (NOS); high-grade B-cell lymphoma (NOS or double/triple hit); transformed follicular lymphoma; follicular lymphoma Grade 3b
-Have disease relapsed or refractory to at least one prior systemic therapy for aggressive non-Hodgkin's lymphoma (aNHL)
-Participants who have received only one prior line of therapy must be ineligible for autologous stem cell transplant (ASCT)
-Measurable disease
-Adequate hepatic, hematologic, and renal function
-Negative HIV test at screening. Participants with a positive HIV test at screening are eligible provided that, prior to enrollment, they are stable on anti-retroviral therapy for at least 4 weeks, have a CD4 count of at least 200 microliters, have an undetectable viral load, and have not had a history of opportunistic infection attributable to AIDS within the last 12 months
-Estimated creatinine clearance (CrCl)>=30 mL/min by Cockroft-Gault method or other institutional standard methods

Exclude criteria

-Pregnant or breast feeding, or intending to become pregnant during the study or within 3 months after the final dose of mosunetuzumab, 9 months after the final dose of polatuzumab vedotin, 12 months after the final dose of rituximab, 6 months after the final dose of gemcitabine, 9 months after the final dose of oxaliplatin, and 3 months after the final dose of tocilizumab, as applicable
-Inability to comply with protocol-mandated activity restrictions
-Prior treatment with mosunetuzumab or other CD-20-directed bispecific antibodies or R-GemOx or Gem-Ox
-Prior treatment with polatuzumab vedotin, with the following exceptions: participants who have a documented response (partial response or complete response) to polatuzumab vedotin and an absence of PD within 12 months from the last dose of polatuzumab vedotin; participants who received up to 2 doses of a polatuzumab vedotin-containing regimen as bridging to CAR-T therapy, and either has a documented disease control (stable disease, partial response, or complete response), or were not assessed for response following treatment with polatuzumab vedotin
-Contraindication to any component of the study treatment
-Grade > 1 peripheral neuropathy
-Received anti-lymphoma treatments with monoclonal antibodies, radio-immunoconjugates or antibody-drug conjugates (ADCs) within 4 weeks before the first dose of study treatment
-Treatment with any chemotherapeutic agent, or treatment with any other anti-cancer agent (investigational or otherwise) within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to the first dose of study treatment
-Treatment with radiotherapy within 2 weeks prior to the first dose of study treatment
-ASCT within 100 days prior to the first study treatment administration
-Prior treatment with chimeric antigen receptor (CAR) T cell therapy within 30 days before the first study treatment administration
-Prior allogenic stem cell transplant (SCT)
-Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
-History of confirmed progressive multifocal leukoencephalopathy
-History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
-History of other malignancy that could affect compliance has been treated with the protocol or interpretation of results, with the exception of malignancies with a negligible risk of metastasis or death.
-Currently have or have had a past history of central nervous system (CNS) involvement of lymphoma
-Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease.
-Significant cardiovascular disease such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina
-Significant active pulmonary disease
-Known or suspected chronic active Epstein-Barr virus (EBV) infection
-Recent major surgery within 4 weeks prior to the first study treatment administration
-Have been administered a live, attenuated vaccine within 4 weeks before the first dose of study treatment administration or anticipation that such a live, attenuated vaccine will be required during the study
-Participants who have positive SARS-CoV-2 test within 7 days prior to enrollment (rapid antigen test result is acceptable)
-History of autoimmune disease
-Received investigational therapy, whether or not intended for lymphoma treatment, within 7 days prior to initiation of study treatment
-Clinically significant history of liver disease, including viral or other hepatitis, or cirrhosis

Related Information

• Primary Sponsor: Shen Yin
• Secondary ID(s): NCT05171647