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

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

Study Overview

• Status: Not yet recruiting
• Conditions: Mantle Cell Lymphoma
• Intervention / Treatment: Drug: Obinutuzumab; Drug: Glofitamab; Drug: Bortezomib; Drug: Orelabrutinib

• Study Type: Interventional
• Enrollment (Estimated): 29
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Glofitamab-Orelabrutinib-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.

Drug: Obinutuzumab; Obinutuzumab pre-treatment is given intravenously at a dose of 2000mg on Cycle 1 Days 1-2; Drug: Glofitamab; Glofitamab is given intravenously at a dose of 2.5mg on Cycle 1 Day 8. Glofitamab is given intravenously at a dose of 10mg on Cycle 1 Day 15. Glofitamab is given intravenously at a dose of 30mg on Day 1 of Cycles 2-6; Drug: Bortezomib; Bortezomib is given intravenously at a dose of 1.6 mg/m² on Days 1, 8, and 15 of Cycles 1-12.; Drug: Orelabrutinib; Orelabrutinib is given orally at a dose of 150 mg daily on Days 1-21 of Cycles 1-12.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response (CR) Rate	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	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	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.	Up to 2 years
Duration of Response (DoR)	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.	Up to 2 years
Duration of Complete Response (DoCR)	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.	Up to 2 years
Progression-Free Survival (PFS)	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.	Up to 2 years
Overall Survival (OS)	OS, defined as the time from the first study treatment to the date of death from any cause.	Up to 2 years
Incidence and severity of adverse events	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	Up to 2 years

Collaborators and Investigators

• Sponsor: Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: October 23, 2024
• First Submitted That Met QC Criteria: October 23, 2024
• First Posted (Actual): October 24, 2024

Study Record Updates

• Last Update Posted (Estimated): November 19, 2024
• Last Update Submitted That Met QC Criteria: November 15, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Mantle-Cell; Antineoplastic Agents, Immunological; Antineoplastic Agents; Bortezomib; Obinutuzumab
• Other Study ID Numbers: Glo-MCL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No