Table 5.
Ongoing trials of signal transduction pathway inhibitors in mature B cell neoplasms.
| Drug | Target | Histologic subtype | Study phase | Schedule | Setting (planned enrollment) | Current trials |
|---|---|---|---|---|---|---|
| BCR INHIBITORS | ||||||
| Acalabrutinib | BTK | HG-BCL | I | IV infusion days 1, 3, 5 | R/R (42 pts) | NCT03527147 |
| Ibrutinib | BTK | MCL | III | 1 tablet/day | Randomized in combination to Venetoclax (287 pts) | NCT03112174 |
| Ibrutinib | BTK | DLBCL | Ib Dose Finding | 1 tablet/day until disease progression | R/R (30 pts) in combination to Rituximab and Venetoclax | NCT03136497 |
| LOXO-305 | BTK C481 mutation | CLL/SLL | I/II | 25 mg/day | R/R with C481 mutation in BTK gene. | NCT03740529 |
| Copanlisib | PI3K | B-NHLnos | Ib/II | Days 1, 8, and 15 of a 28-day cycle | R/R (25 pts) | NCT02342665 |
| Duvelisib | PI3Kδ+γ | CLL/SLL | I/II | Orally twice daily | R/R (47 pts) in combination with Venetoclax | NCT03534323 |
| Idelalisib | PI3K δ | CLL/SLL iNHL | II | 1 tablet/day (cycle 21 day) | R/R (68 pts). Combination to Pembrolizumab | NCT02332980 |
| Cerdulatinib (PRT062070) | SYKJAK 1-2 | FL, DLBCL | I/IIa | Dose finding | R/R (283 pts) | NCT01994382 |
| TAK659 | SYK/FLT3 | FL, MZL | I | 60–80 mg/day | R/R (47 pts). Single agent | NCT03238651 |
| PROTEASOME INHIBITORS | ||||||
| Bortezomib | PIs | B-NHLnos | I/II | MTD | R/R (56 pts). Combination to Gemcitabime and Rituximab | NCT00863369 |
| Ixazomib | 20S subunit | iNHL | II | once weekly × 4 wk | naïve iNHL (36 pts). In addition to Rituximab sd | NCT02339922 |
| mTor- INHIBITORS | ||||||
| Temsirolimus | mTor | Lymphoblastic Lymphoma | I | Day 1-8 IV | R/R (30 pts). in combination to Etoposide and Cyclophosphamide | NCT01614197 |
| BCL2 INHIBITOR | ||||||
| Venetoclax | BH3 domain | DLBCL | Ib | 1 tablet/day (cycle 28 day) | R/R (30 pts). In combination with Rituximab with 17p deletion | NCT03136497 |
| HDAC INHIBITORS | ||||||
| CUDC-907 | Class I and II+ PI3K | DLBCL | II | ND | R/R (200 pts) with Myc alteration | NCT02674750 |
| Mocetinostat (MGCD0103) | Class I and IV | DLBCL | II | 70 mg/3 times per week on a 28 day | R/R (7 pts) with mutations of Acetyltransferase Genes | NCT02282358 |
| Panobinostat | Class I, II and IV | DLBCL | II | 30 mg/day | R/R (42 pts). Randomized with or without Rituximab | NCT01238692 |
| Tazemetostat | EZH2 | DLBCL FL | I/II | Dose escalation | Single agent (420 pts) | NCT01897571 |
| Vorinostat | Class I and II | DLBCL, FL | I | Days 1–5 and 8–12. Cycle 21 days | R/R (60 pts). In combination to Pembrolizumab | NCT03150329 |
ASCT, Autologous Stem Cell Transplantation; B-NHL, B-NHL not otherwise specified; CLL/SLL, Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia; DLBCL, Diffuse Large B cell Lymphoma; FL, Follicular Lymphoma; HG-BCL, High Grade B-cell lymphoma; IGHV, Immunoglobulin G Heavy Variable chain; iNHL, indolent NHL; IV, intravenous; LBCL Large B-cell lymphoma; MCL, Mantle Cell Lymphoma; mo.s, months; MZL, Marginal Zone Lymphoma; ND, Not Documented NR, Not Reached; pts, patients; R-CVEP, rituximab, cyclophosphamide, vorinostat, etoposide, and prednisone; R/R, Refractory/relapsed; y, years; MTD, maximum tolerated dose; wk, week; sd, standard dosage.