Summary of key ongoing trials in Richter transformation (RT)
| Trial name and identifier . | Planned enrollment . | Trial design . | Novel treatment . |
|---|---|---|---|
| Bispecific antibody | |||
| EPCORE CLL-1, NCT04623541 | 102 (RT and CLL) | Single-arm phase 2 | Anti-CD20/CD3 bispecific antibody in recruiting patients with CLL or RT |
| Doublet/triplet combination | |||
| GCLLSG CLL-RT1, NCT04271956 | 52 | Single-arm phase 2 | Tislelizumab, a PD1 inhibitor, with zanubrutinib, a 2nd BTK inhibitor in R/R or 1 L RT |
| Israeli CLL Study Group, GIVeRS, NCT04939363 | 15 | Single-arm phase 2 | Obinutuzumab, ibrutinib, and venetoclax for 1 L or R/R RT |
| Acalabrutinib, Venetoclax and Durvalumab for the Treatment of RT, NCT05388006 | 33 | Single-arm phase 2 | Time-limited acalabrutinib, venetoclax, and durvalumab for patients with 1 L RT |
| Atezolizumab (PD-L1 mAb) in Combination With Obinutuzumab and Venetoclax for Patients With Chronic Lymphocytic Leukemia and Richter Transformation, NCT02846623 | 65 (RT and CLL) | Single-arm phase 2 | Time-limited atezolizumab, venetoclax, and obinutuzumab for patients with 1 L RT |
| Pirtobrutinib, Venetoclax, and Obinutuzumab, NCT05536349 | 60 (RT and CLL) | Single-arm phase 2 | Time-limited pirtobrutinib, venetoclax, and obinutuzumab for patients with 1 L CLL or RT |
| BTK inhibition | |||
| BRUIN, NCT03740529 | 82 | Single-arm phase 1/2 | Pirtobrutinib monotherapy in 1 L and R/R RT |
| Chemoimmunotherapy plus targeted inhibitor | |||
| NCRI STELLAR trial, NCT03899337 | 60 | Randomized phase 2 | R-CHOP versus R-CHOP-acalabrutinib in 1 L RT |
| Venetoclax Plus Dose-Adjusted R-EPOCH or R-CHOP for RT, NCT03054896 | 66 | Single-arm phase 2 | Venetoclax plus dose-adjusted R-EPOCH (N = 26) or R-CHOP (N = 40) for 1 L RT |
| CAR-T–based combinations | |||
| Lisocabtagene Maraleucel, Nivolumab and Ibrutinib for the Treatment of RT, NCT05672173 | 20 | Single-arm phase 2 | Lisocabtagene maraleucel, nivolumab, and ibrutinib |
| Trial name and identifier . | Planned enrollment . | Trial design . | Novel treatment . |
|---|---|---|---|
| Bispecific antibody | |||
| EPCORE CLL-1, NCT04623541 | 102 (RT and CLL) | Single-arm phase 2 | Anti-CD20/CD3 bispecific antibody in recruiting patients with CLL or RT |
| Doublet/triplet combination | |||
| GCLLSG CLL-RT1, NCT04271956 | 52 | Single-arm phase 2 | Tislelizumab, a PD1 inhibitor, with zanubrutinib, a 2nd BTK inhibitor in R/R or 1 L RT |
| Israeli CLL Study Group, GIVeRS, NCT04939363 | 15 | Single-arm phase 2 | Obinutuzumab, ibrutinib, and venetoclax for 1 L or R/R RT |
| Acalabrutinib, Venetoclax and Durvalumab for the Treatment of RT, NCT05388006 | 33 | Single-arm phase 2 | Time-limited acalabrutinib, venetoclax, and durvalumab for patients with 1 L RT |
| Atezolizumab (PD-L1 mAb) in Combination With Obinutuzumab and Venetoclax for Patients With Chronic Lymphocytic Leukemia and Richter Transformation, NCT02846623 | 65 (RT and CLL) | Single-arm phase 2 | Time-limited atezolizumab, venetoclax, and obinutuzumab for patients with 1 L RT |
| Pirtobrutinib, Venetoclax, and Obinutuzumab, NCT05536349 | 60 (RT and CLL) | Single-arm phase 2 | Time-limited pirtobrutinib, venetoclax, and obinutuzumab for patients with 1 L CLL or RT |
| BTK inhibition | |||
| BRUIN, NCT03740529 | 82 | Single-arm phase 1/2 | Pirtobrutinib monotherapy in 1 L and R/R RT |
| Chemoimmunotherapy plus targeted inhibitor | |||
| NCRI STELLAR trial, NCT03899337 | 60 | Randomized phase 2 | R-CHOP versus R-CHOP-acalabrutinib in 1 L RT |
| Venetoclax Plus Dose-Adjusted R-EPOCH or R-CHOP for RT, NCT03054896 | 66 | Single-arm phase 2 | Venetoclax plus dose-adjusted R-EPOCH (N = 26) or R-CHOP (N = 40) for 1 L RT |
| CAR-T–based combinations | |||
| Lisocabtagene Maraleucel, Nivolumab and Ibrutinib for the Treatment of RT, NCT05672173 | 20 | Single-arm phase 2 | Lisocabtagene maraleucel, nivolumab, and ibrutinib |
BTK, Bruton tyrosine kinase; CAR-T, chimeric antigen receptor T cell; CHOP-R, doxorubicin, vincristine, cyclophosphamide, prednisolone, rituximab; CLL, chronic lymphocytic leukemia; EPOCH-R, etoposide, doxorubicin, vincristine, cyclophosphamide, prednisolone, rituximab; GCLLSG, German chronic lymphocytic leukemia study group; NCRI, National Cancer Research Institute; R/R, relapsed/refractory; RT, Richter transformation.