Mantle Cell Lymphoma
Conditions
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
Interventions
DRUGObinutuzumab
Obinutuzumab pre-treatment is given intravenously at a dose of 2000mg on Cycle 1 Days 1-2
DRUGGlofitamab
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
DRUGBortezomib
Bortezomib is given intravenously at a dose of 1.6 mg/m² on Days 1, 8, and 15 of Cycles 1-12.
DRUGOrelabrutinib
Orelabrutinib is given orally at a dose of 150 mg daily on Days 1-21 of Cycles 1-12.
Sponsors
Ruijin Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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 |
| 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. |
Outcome results
None listed