A Prospective, Single-Center Study Evaluating the Efficacy and Safety of Glofitamab Combined With Orelabrutinib and Bortezomib in Patients With High-Risk Mantle Cell Lymphoma

Phase 2

Not yet recruiting

• Conditions: Mantle Cell Lymphoma
• Interventions: Drug: Obinutuzumab; Drug: Glofitamab; Drug: Bortezomib; Drug: Orelabrutinib

• Registration Number: NCT06656221
• Lead Sponsor: Ruijin Hospital

Brief Summary

The aim of this study is to evaluate the efficacy and safety of Glofitamab combined with Orelabrutinib and Bortezomib in patients with high-risk mantle cell lymphoma

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design

Study Timeline

• Study First Submitted: 2024-10-23
• Study First Submitted QC: 2024-10-23
• Study First Posted: 2024-10-24
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-15
• Last Update Posted: 2024-11-19
• Study Start: 2024-12-01
• Primary Completion: 2026-12-01
• Study Completion: 2028-05-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 29

Inclusion Criteria

• Signed Informed Consent Form
• Age ≥ 18 years at the time of signing Informed Consent Form and willingness to comply with study protocol procedures
• Participants with MCL
• Meets any of the following high-risk criteria: blastoid/pleomorphic morphology; high Ki-67 (≥ 30%); TP53 aberration; del(17p); complex karyotype; MIPI score ≥ 6.2; early progression after first-line treatment (<24 months); presence of other high-risk genetic mutations (KMT2D, NSD2, NOTCH1, CDKN2A, NOTCH2, SMARCA4, CCND1)
• Life expectancy ≥ 12 weeks
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1, or 2
• At least one bi-dimensionally measurable (≥ 1.5 cm) nodal lesion, or one bi-dimensionally measurable (≥ 1 cm) extranodal lesion, as measured on CT scan
• No bone marrow involvement: ANC ≥ 1.0 × 10^9/L; bone marrow involvement: ANC ≥ 0.5 × 10^9/L
• No bone marrow involvement: PLT ≥ 75 × 10^9/L; bone marrow involvement: PLT ≥ 25 × 10^9/L
• No bone marrow involvement: Hgb ≥ 8 g/dL; bone marrow involvement: Hgb ≥ 7 g/dL
• Adequate renal function, defined as measured or estimated creatinine clearance ≥ 30 mL/min

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Exclusion Criteria

• Contraindication to any of the individual components of Glofit-Orela-Borte
• Known active infection at the time of enrollment
• Positive test results for chronic hepatitis B infection (defined as positive hepatitis B surface antigen [HBsAg] serology): Patients with occult or prior HBV infection (defined as negative HbsAg and positive hepatitis B core antibody [HbcAb]) may be included if HBV DNA is undetectable, provided that they are willing to undergo DNA testing on Day 1 of every cycle and every three months for at least 12 months after the last cycle of study treatment and appropriate antiviral therapy
• Positive test results for hepatitis C (hepatitis C virus [HCV] antibody serology testing): Patients who are positive for HCV antibody are eligible only if PCR is negative for HCV RNA
• History of other malignancies that could affect compliance with the protocol or interpretation of results
• Active autoimmune disease requiring treatment
• Primary or secondary CNS lymphoma at the time of recruitment
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk from treatment complications

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Glofitamab-Orelabrutinib-Bortezomib	Obinutuzumab	Participants will receive 2000 mg of obinutuzumab on Days 1-2 of Cycle 1, 2.5 mg of glofitamab on Day 8 of Cycle 1, 10 mg of glofitamab on Day 15 of Cycle 1, followed by 30 mg of glofitamab on Day 1 of Cycles 2-12. Participants will receive 1.6 mg/m² of bortezomib on Days 1, 8, and 15 of Cycles 1-12. Participants will receive 150 mg/day of orelabrutinib on Days 1-21of Cycles 1-12. The duration of one cycle is 21 days.
Glofitamab-Orelabrutinib-Bortezomib	Glofitamab	Participants will receive 2000 mg of obinutuzumab on Days 1-2 of Cycle 1, 2.5 mg of glofitamab on Day 8 of Cycle 1, 10 mg of glofitamab on Day 15 of Cycle 1, followed by 30 mg of glofitamab on Day 1 of Cycles 2-12. Participants will receive 1.6 mg/m² of bortezomib on Days 1, 8, and 15 of Cycles 1-12. Participants will receive 150 mg/day of orelabrutinib on Days 1-21of Cycles 1-12. The duration of one cycle is 21 days.
Glofitamab-Orelabrutinib-Bortezomib	Bortezomib	Participants will receive 2000 mg of obinutuzumab on Days 1-2 of Cycle 1, 2.5 mg of glofitamab on Day 8 of Cycle 1, 10 mg of glofitamab on Day 15 of Cycle 1, followed by 30 mg of glofitamab on Day 1 of Cycles 2-12. Participants will receive 1.6 mg/m² of bortezomib on Days 1, 8, and 15 of Cycles 1-12. Participants will receive 150 mg/day of orelabrutinib on Days 1-21of Cycles 1-12. The duration of one cycle is 21 days.
Glofitamab-Orelabrutinib-Bortezomib	Orelabrutinib	Participants will receive 2000 mg of obinutuzumab on Days 1-2 of Cycle 1, 2.5 mg of glofitamab on Day 8 of Cycle 1, 10 mg of glofitamab on Day 15 of Cycle 1, followed by 30 mg of glofitamab on Day 1 of Cycles 2-12. Participants will receive 1.6 mg/m² of bortezomib on Days 1, 8, and 15 of Cycles 1-12. Participants will receive 150 mg/day of orelabrutinib on Days 1-21of Cycles 1-12. The duration of one cycle is 21 days.

Primary Outcome Measures

Name	Time	Method
Complete Response (CR) Rate	Up to 2 years	CR rate, defined as the proportion of patients with a best overall response of CR at any time during the study, as determined by the investigator using 2014 Lugano Response Criteria

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	Up to 2 years	ORR, defined as the proportion of patients with a best overall response of CR or PR at any time during the study, as determined by the investigator using 2014 Lugano Response Criteria.
Duration of Response (DoR)	Up to 2 years	DoR, defined as the time from the first occurrence of a documented objective response (PR or CR) to disease progression or death from any cause (whichever occurs first) according to the 2014 Lugano Response Criteria, as determined by the investigator.
Duration of Complete Response (DoCR)	Up to 2 years	DoCR, defined as the time from the first occurrence of a documented CR to disease progression or death from any cause (whichever occurs first) according to the 2014 Lugano Response Criteria, as determined by the investigator.
Progression-Free Survival (PFS)	Up to 2 years	PFS, defined as the time from the first study treatment to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator using 2014 Lugano Response Criteria.
Overall Survival (OS)	Up to 2 years	OS, defined as the time from the first study treatment to the date of death from any cause.
Incidence and severity of adverse events	Up to 2 years	Incidence and severity of adverse events, with severity determined according to the NCI CTCAE v5.0 grading scale, except CRS that shall be graded using ASTCT CRS grading criteria 2019