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

NCT06656221 | Not Yet Recruiting Phase 2

• 1 other identifier: Glo-MCL
• Study Type: interventional
• Target: 29
• Locations: 0 countries
• Sites: N/A

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

Conditions

Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Objective Response Rate (ORR)

  Up to 2 years

• Duration of Response (DoR)

  Up to 2 years

• Duration of Complete Response (DoCR)

  Up to 2 years

• Progression-Free Survival (PFS)

  Up to 2 years

• Overall Survival (OS)

  Up to 2 years

Study Arms (1)

Glofitamab-Orelabrutinib-Bortezomib

EXPERIMENTAL

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; Drug: Glofitamab; Drug: Bortezomib; Drug: Orelabrutinib

Interventions

Obinutuzumab DRUG

Obinutuzumab pre-treatment is given intravenously at a dose of 2000mg on Cycle 1 Days 1-2

Glofitamab-Orelabrutinib-Bortezomib

Glofitamab DRUG

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

Glofitamab-Orelabrutinib-Bortezomib

Bortezomib DRUG

Bortezomib is given intravenously at a dose of 1.6 mg/m² on Days 1, 8, and 15 of Cycles 1-12.

Glofitamab-Orelabrutinib-Bortezomib

Orelabrutinib DRUG

Orelabrutinib is given orally at a dose of 150 mg daily on Days 1-21 of Cycles 1-12.

Glofitamab-Orelabrutinib-Bortezomib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ruijin Hospital: lead

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

obinutuzumab; glofitamab; Bortezomib; orelabrutinib

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: October 23, 2024
• First Posted: October 24, 2024
• Study Start: December 1, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): May 1, 2028
• Last Updated: November 19, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share