Lymphoma
Conditions
Brief summary
This Phase II, open-label, multicenter study will evaluate the safety, efficacy, and pharmacokinetics of glofitamab in combination with rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in individuals with circulating tumor DNA (ctDNA) high-risk diffuse large B-cell lymphoma (DLBCL), as the first line of treatment.
Interventions
DRUGGlofitamab
Participants will receive intravenous (IV) glofitamab as per schedule specified in the treatment arm.
DRUGTocilizumab
Participants will receive tocilizumab as needed to manage cytokine release syndrome (CRS).
DRUGDoxorubicin
Participants will receive 50 mg/m2 body surface area of doxorubicin IV as per schedule specified in the treatment arm.
DRUGVincristine
Participants will receive 1.4 mg/m2 body surface area of vincristine IV as per schedule specified in the treatment arm.
DRUGPrednisone
Participants will receive 100 mg of prednisone or prednisolone as per schedule specified in the treatment arm.
DRUGRituximab
Participants will receive 375 mg/m2 body surface area of rituximab IV as per schedule specified in the treatment arm.
DRUGCyclophosphamide
Participants will receive 750 mg/m2 body surface area of cyclophosphamide IV as per schedule specified in the treatment arm.
Sponsors
Hoffmann-La Roche
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
* Previously untreated patients with CD20-positive DLBCL, including one of the following diagnoses made according to the 2016 World Health Organization (WHO) classification of lymphoid neoplasms * DLBCL, not otherwise specified, including GCB and ABC/non-GCB types as well as double-expressor lymphoma (coexpression of MYC and BCL2) * High-grade B-cell lymphoma (HGBCL) with MYC and BCL2 and/or BCL6 translocations * Patients with de novo transformed follicular lymphoma (patients with discordant bone marrow involvement, i.e., evidence of low-grade histology in bone marrow) may be considered after discussion with the Medical Monitor * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 * International Prognostic Index (IPI): 2-5 * Life expectancy of at least 6 months * Adequate biomarker blood samples prior to initiation of R-CHOP on Day 1 of Cycle 1 and on Day 1 of Cycle 2 submitted for screening for determination of ctDNA status * At least one bi-dimensionally fluorodeoxyglucose (FDG)-avid measurable lymphoma lesion on positron emission tomography/computed tomography (PET/CT) scan * Left ventricular ejection fraction (LVEF) \>=50%, as determined on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO) * Adequate hematopoietic function * Contraception use Additional Inclusion Criterion for ctDNA High-Risk Participants: * Plasma sample evaluated to be ctDNA high risk
Exclusion criteria
* Current diagnosis of B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classic Hodgkin lymphoma (gray-zone lymphoma), primary mediastinal (thymic) large B-cell lymphoma, T-cell/histiocyte-rich large B-cell lymphoma, Burkitt lymphoma, central nervous system (CNS) lymphoma (primary or secondary involvement), primary effusion DLBCL, and primary cutaneous DLBCL * Contraindication to any of the individual components of R-CHOP, including prior receipt of anthracyclines, history of severe allergic or anaphylactic reactions to murine monoclonal antibodies, or known sensitivity or allergy to murine products * Prior treatment for indolent lymphoma * Prior solid organ or allogeneic stem cell transplant * Prior therapy for DLBCL and high-grade B-cell lymphoma (HGBCL) with the exception of palliative, short-term treatment with corticosteroids * Pregnant or breastfeeding, or intending to become pregnant during the study or within 12 months after the final dose of R-CHOP, 3 months after the final dose of tocilizumab (if applicable), or 2 months after the final dose of glofitamab
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| End of Treatment Complete Response (EOT CR) Rate | Up to approximately 24 months |
Secondary
| Measure | Time frame |
|---|---|
| Overall Response Rate (ORR) at the EOT | Up to approximately 24 months |
| Progression-free Survival (PFS) | Up to approximately 24 months |
| Overall Survival (OS) | Up to approximately 24 months |
| Percentage of Participants With Adverse Events (AEs) | Up to 90 days after the final dose of study treatment |
| Serum Concentration of Glofitamab | At pre-defined intervals up to approximately 10 months |
| Maximum Concentration (Cmax) of Glofitamab | At pre-defined intervals up to approximately 10 months |
| Total Exposure (AUC) of Glofitamab | At pre-defined intervals up to approximately 10 months |
Countries
Denmark, France, Netherlands, Poland, Spain, United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 64.0 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 12 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 10 Participants |
| Race (NIH/OMB) White | 32 Participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 45 |
| other Total, other adverse events | 40 / 45 |
| serious Total, serious adverse events | 20 / 45 |
Outcome results
None listed