Brief Summary:
The purpose of this study is to compare the effectiveness and safety of golcadomide in
combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone
(R-CHOP) chemotherapy vs placebo in combination with R-CHOP chemotherapy in participants with
previously untreated high-risk large B-cell lymphoma (LBCL).
Inclusion Criteria:
- Histologically confirmed (per local evaluation) diagnosis of de novo, previously
untreated large B-cell lymphoma (LBCL) according to 2022 world health organization (WHO)
classification including:
i) Diffuse large B-cell lymphoma (DLBCL), not otherwise specified [including germinal
center B-cell (GCB) and activated B-cell (ABC) types]
ii) High-grade B-cell lymphoma, with MYC and BCL2 rearrangements
iii) High-grade B-cell lymphoma, not otherwise specified
iv) T-cell/histiocyte/rich large B-cell lymphoma (THRLBCL)
v) Epstein-Barr virus + DLBCL
- International Prognostic Index (IPI) score 1 or 2 with lactate dehydrogenase (LDH) ≥
1.3 x upper limit of normal (ULN) and/or bulky disease defined as single lesion of ≥ 7
cm OR IPI ≥ 3.
- Measurable disease defined by at least 1 fluorodeoxyglucose (FDG)-avid lesion for
FDG-avid subtype and 1 bi-dimensionally measurable (> 1.5 cm in longest diameter)
disease by computed tomography (CT) or magnetic resonance imaging (MRI), as defined by
the Lugano classification.
- Must have Ann Arbor Stage II-IV disease.
Exclusion Criteria:
- Any significant medical condition, active infection, laboratory abnormality, or
psychiatric illness that would prevent the participant from participating in the
study.
- Any other subtype of lymphoma. Cases of primary mediastinal (thymic) large B-cell
lymphoma (PMBCL), primary cutaneous DLBCL-leg type, Grade 3b FL, FL transformed to
a-BCL, Anaplastic lymphoma kinase (ALK) positive large B-cell lymphoma, primary
effusion lymphoma, and Burkitt lymphoma.
- Documented or suspected central nervous system (CNS) involvement by lymphoma.
- Other protocol-defined Inclusion/Exclusion criteria apply.
Primary outcome:
1. Progression-free survival (PFS) assessed by the Investigator (Time Frame - Up to approximately 67 months)
Secondary outcome:
1. Overall survival (OS) (Time Frame - Up to approximately 67 months)
2. Event-free survival (EFS) (Time Frame - Up to approximately 67 months)
3. Complete Metabolic Response assessed by the Independent Response Adjudication Committee (IRAC) (Time Frame - Up to approximately 18 weeks)
4. Minimal residual disease (MRD) negativity rate (Time Frame - Up to approximately 18 weeks)
5. Progression-free survival (PFS) assessed by the IRAC (Time Frame - Up to approximately 47 months)
6. Objective response (OR) assessed by the Investigator (Time Frame - Up to approximately 18 weeks)
7. Complete metabolic response (CMR) assessed by the Investigator (Time Frame - Up to approximately 18 weeks)
8. PFS24 assessed by the Investigator 24 months after randomization (Time Frame - Up to 24 months)
9. Duration of response (DoR) (Time Frame - Up to approximately 67 months)
10. Second progression-free survival (PFS2) assessed by the Investigator (Time Frame - Up to approximately 67 months)
11. Relative dose intensity (%) (Time Frame - Up to 18 weeks)
12. Time from randomization to meaningful improvement in primary domains of interest in the European Organization for Research and Treatment of Cancer - Quality of Life C30 (EORTC QLQ-C30) Questionnaire (Time Frame - Up to approximately 67 months)
13. Time from randomization to meaningful improvement in primary domains of interest in the Functional Assessment of Cancer Treatment-Lymphoma (FACT-LymS) Questionnaire (Time Frame - Up to approximately 67 months)
14. Mean change from baseline in the EORTC QLQ-C30 (Time Frame - Up to approximately 67 months)
15. Mean change from baseline in the FACT-LymS (Time Frame - Up to approximately 67 months)
16. Number of participants with Adverse Events (AEs) (Time Frame - Up to approximately 20 weeks)
17. Number of participants with treatment-emergent adverse events (TEAEs) (Time Frame - Up to approximately 20 weeks)
18. Number of participants with laboratory abnormalities (Time Frame - Up to approximately 20 weeks)
19. Number of participants with vital sign abnormalities (Time Frame - Up to approximately 20 weeks)
- Experimental: Golcadomide + R-CHOP (Rituximab, Doxorubicin, Vincristine, Cyclophosphamide, Prednisone)
- Placebo Comparator: Placebo + R-CHOP
- Golcadomide (BMS-986369 / CC-99282 / ):
Specified dose on specified days - Placebo:
Specified dose on specified days - Rituximab:
Specified dose on specified days - Cyclophosphamide:
Specified dose on specified days - Doxorubicin:
Specified dose on specified days - Vincristine:
Specified dose on specified days - Prednisone:
Specified dose on specified days
Quelle: ClinicalTrials.gov
