Selected trials designed to overcome resistance or intolerance to targeted therapies in CLL
| ClinicalTrials.gov ID . | Resistance . | Treatment . | Target . | Strategy . | Study phase . | Comment . |
|---|---|---|---|---|---|---|
| NCT03513562 | Ibrutinib | Ibrutinib + venetoclax | BTK, BCL-2 | Combination | 2 | CLL with genetic mutations after ibrutinib treatment |
| NCT03943342 | Ibrutinib | Ibrutinib + venetoclax | BTK, BCL-2 | Combination | 2 | CLL resistant to ibrutinib |
| NCT03128879 | Ibrutinib | Ibrutinib + venetoclax | BTK, BCL-2 | Combination | 2 | CLL with BTK mutation |
| NCT04209621 | Ibrutinib | Ibrutinib + duvelisib | BTK, PI3K | Combination | 2 | BTK and/or PLCG2 mutations and/or progressive CLL |
| NCT03422393 | Ibrutinib | Ibrutinib + venetoclax | BTK, BCL-2 | Combination | 1 | CLL progressing on single agent ibrutinib |
| NCT03370185 | BTKi | Duvelisib | PI3K | Sequencing | 2 | CLL relapsed/refractory to BTKi, or discontinued due to toxicity |
| NCT04149821 | BTKi or BCL-2i | Umbralisib + ublituximab | PI3K, CD20 | Sequencing | 2 | CLL progressed on a BTKi or BCL-2i |
| NCT03037645 | SoC including BTKi | Vecabrutinib (SNS-062) | BTK (reversible) | Next-generation therapy | 1/2 | CLL failed standard of care therapies including a BTKi |
| NCT03740529 | SoC | LOXO-305 ± venetoclax, rituximab, R-CHOP | BTK (reversible), BCL-2, CIT | Next-generation therapy | 1/2 | CLL failed or intolerant to standard of care |
| NCT02968563 | BCL-2i, BTKi, PI3Ki, SYKi, or obinutuzumab | Tirabrutinib ± idelalisib ± obinutuzumab | BTK (irreversible), PI3K, CD20 | Next-generation therapy | 2 | Progression on treatment with any BTKi, SYKi, PI3Ki, BCL-2i, or obinutuzumab |
| ClinicalTrials.gov ID . | Resistance . | Treatment . | Target . | Strategy . | Study phase . | Comment . |
|---|---|---|---|---|---|---|
| NCT03513562 | Ibrutinib | Ibrutinib + venetoclax | BTK, BCL-2 | Combination | 2 | CLL with genetic mutations after ibrutinib treatment |
| NCT03943342 | Ibrutinib | Ibrutinib + venetoclax | BTK, BCL-2 | Combination | 2 | CLL resistant to ibrutinib |
| NCT03128879 | Ibrutinib | Ibrutinib + venetoclax | BTK, BCL-2 | Combination | 2 | CLL with BTK mutation |
| NCT04209621 | Ibrutinib | Ibrutinib + duvelisib | BTK, PI3K | Combination | 2 | BTK and/or PLCG2 mutations and/or progressive CLL |
| NCT03422393 | Ibrutinib | Ibrutinib + venetoclax | BTK, BCL-2 | Combination | 1 | CLL progressing on single agent ibrutinib |
| NCT03370185 | BTKi | Duvelisib | PI3K | Sequencing | 2 | CLL relapsed/refractory to BTKi, or discontinued due to toxicity |
| NCT04149821 | BTKi or BCL-2i | Umbralisib + ublituximab | PI3K, CD20 | Sequencing | 2 | CLL progressed on a BTKi or BCL-2i |
| NCT03037645 | SoC including BTKi | Vecabrutinib (SNS-062) | BTK (reversible) | Next-generation therapy | 1/2 | CLL failed standard of care therapies including a BTKi |
| NCT03740529 | SoC | LOXO-305 ± venetoclax, rituximab, R-CHOP | BTK (reversible), BCL-2, CIT | Next-generation therapy | 1/2 | CLL failed or intolerant to standard of care |
| NCT02968563 | BCL-2i, BTKi, PI3Ki, SYKi, or obinutuzumab | Tirabrutinib ± idelalisib ± obinutuzumab | BTK (irreversible), PI3K, CD20 | Next-generation therapy | 2 | Progression on treatment with any BTKi, SYKi, PI3Ki, BCL-2i, or obinutuzumab |
CIT, chemoimmunotherapy; R-CHOP, rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone; SoC, standard of care; SYK, spleen tyrosine kinase.