Table 2.
Clinical studies evaluating HDACis for the treatment of MM
| NCT number | Phase | Patients | Regimens | HDACis dose/Schedule | Response rates | Grade 3/4 toxicities | References |
|---|---|---|---|---|---|---|---|
| NCT00445068 | II | n = 38 | Panobinostat | 20 mg, Days 1, 3, 5, 8, 10, 12, every 21 days | ORR: 2.63% | Thrombocytopeni (50%), anemia (11.2%), neutropenia (8%), fatigue (26%) | [86] |
| NCT00621244 | Ia/II | n = 176 | Panobinostat | From 20-80 mg three times a week or once every 14 days | Not found | Thrombocytopenia (41.5%), neutropenia (21%), fatigue (21%) | [87] |
| NCT01720875 | II | n = 16 | Vorinostat/ Bortezomib/ Dexamethasone | 400 mg, Days 1–14, every 21 days | ORR: 81.3% | Thrombocytopenia (50%), diarrhea (6.3%), fatigue (6.3%), anemia (6.3%) | [88] |
| NCT01583283 | I | n = 38 | ACY-1215/ Lenalidomide/ Dexamethasone | From 40–240 mg once daily to 160 mg twice daily | ORR: 55% | Fatigue (18%), diarrhea (5%) | [89] |
| NCT01502085 | I/II | n = 25 | Vorinostat/ Lenalinomide/ Dexamethasone | Vorinostat: 400 mg once a week; Lenalidomide: 25 mg once two weeks; Dexamethasone: 40 mg, Days 1, 8, 15 and 22 | ORR: 24% | Thrombocytopenia (56%), fatigue (72%), diarrhea (72%), neutropenia (68%), vomiting (12%) | [90] |
| NCT00642954 | I | n = 31 | Vorinostat/ Lenalidomide/ Dexamethasone | Vorinostat: 400 m, days 1–7 and 15–21; Lenalidomide: 25 mg, days 1–21; Dexamethasone: 40 mg, Days 1, 8, 15, 22, every 28 days | ORR: 47% | Anemia (58%), thrombocytopenia (58%), diarrhea (55%), fatigue (55%), cough (45%) | [91] |
| NCT02290431 | II | n = 31 | Panobinostat/ Bortezomib/ Dexamethasone | 20 mg, Days 1, 3, 5, 8, 10, 12, every 21 days | ORR: 80.6% | Thrombocytopenia (48.4%), fatigue (25.8%), diarrhea (22.6%), neutropenia (22.6%), lymphopenia (22.6%) | [93] |
| NCT01440582 | I | n = 55 | Panobinostat/ Bortezomib/ Lenalidomide/ Dexamethasone | Bortezomib: (1.3 mg/m2), Days 1, 4, 8, 11; Lenalidomide: 25 mg, Days 1–14; Dexamethasone: 20 mg, Days 1, 2, 4, 5, 8, 9, 11, 12 | Not found | Thrombocytopenia (17%), diarrhea (17%) | [94] |
| NCT02654990 | II | n = 248 | Panobinostat/ Bortezomib/ Dexamethasone | 82 to panobinostat 20 mg thrice weekly, 83 to panobinostat 20 mg twice weekly, and 83 to 10 mg panobinostat three times weekly | ORR: 62·2% (20 mg three times weekly group); 65·1% (20 mg twice weekly group), 50·6% (10 mg three times weekly group) | Thrombocytopenia (32%), neutropenia (15.2%), pneumonia (11.6%) | [95] |
| NCT01083602 | II | n = 55 | Panobinostat/ Bortezomib/ Dexamethasone | 20 mg, Days 1, 3, 5, 8, 10, 12, every 21 days | ORR: 34.5% | Thrombocytopenia (63.6%), diarrhea (20%), fatigue (20%), anemia (14.5%), neutropenia (14.5%), pneumonia (14.5%) | [96] |
| NCT00773838 | II | n = 143 | Vorinostat/ Bortezomib/ Dexamethasone | 400 mg, Days 1–14, every 21 days | ORR: 11.3% | Diarrhea (4.2%), asthenia (2.8%), thrombocytopenia ( 2.8%), pneumonia ( 2.1%), neuralgia (1.4%) | [97] |
| NCT00858234 | I | n = 9 | Vorinostat/ Bortezomib | 400 mg, Days 1–14, every 21 days | ORR: 44% | Thrombocytopenia (100%), lymphopenia (43%), neutropenia (29%), anemia (29%), nausea (29%), dehydration (29%), pneumonia (29%), diarrhea (14%), decreased appetite (14%), fatigue (14%), hypokalemia (14%) | [101] |
| NCT01023308 | III | n = 768 | Panobinostat/ Bortezomib/ Dexamethasone/ Placebo | Panobinostat: 20 mg (hard gelatin capsules); Bortezomib: 1.3 mg/m2 as a 3 to 5 s bolus intravenous injection; Dexamethasone: 20 mg every day | ORR: 60.7% | Pneumonia (14.7%), thrombocytopenia (7.35%), diarrhea (11.29%) anemia (3.67%), vomiting (3.15%), asthenia (3.94%), fatigue (2.89%) pyrexia (4.20%), | [102] |
| NCT01549431 | I | n = 32 | Panobinostat/ Carfilzomib | 20 mg, Days 1, 3, 5, 15, 17, 19, every 28 days | ORR: 63% | Thrombocytopenia (41%), fatigue (17%), nausea (12%), vomiting (12%) | [103] |
| NCT01496118 | I/II | n = 80 | Panobinostat/ Carfilzomib | 20 mg, 30 mg, Days 1, 3, 5, 15, 17, 19, every 28 days | ORR: 84.4% | Thrombocytopenia (60.6%), fatigue (18.2%), anemia (12.1%), dyspnea (12.1%), diarrhea (9.1%), neutropenia (9.1%), nausea (6.1%), vomiting (6.1%), peripheral neuropathy (3%) | [104, 105] |
| NCT01464112 | I | n = 18 | JNJ-2641585 / VELCADE / Dexamethasone | JNJ-2641585: 10 mg three times weekly oral dose with VELCADE + Dexamethasone | ORR: 88.2% | Thrombocytopenia (61.1%), asthenia (55.6%), diarrhea (66.7%) | [110] |
| NCT00773747 | III | n = 637 | Vorinostat/ Bortezomib | 400 mg, Days 1–14, every 21 days | ORR: 11.3% | Thrombocytopenia (45%), neutropenia (28%), anaemia (17%) | [111] |
| NCT00532389 | Ib | n = 62 | Panobinostat/ Bortezomib | Panobinostat 20 mg thrice weekly every week + Bortezomib 1.3 mg/m2, every 21 days | ORR: 73.3% | Thrombocytopenia (85.1%), neutropenia (63.8%), asthenia (29.8%), fatigue (20.0%) | [112] |
| NCT00742027 | II | n = 27 | Panobinostat/ Lenalidomide/ Dexamethasone | 20 mg, Days 1, 3, 5, 15, 17, 19, every 28 days | ORR: 41% | Neutropenia (59%), thrombocytopenia (31%), fatigue (12.5%), infection (15.6%), diarrhea (9.4%) anemia (5%) | [113] |
ORR: overall response rate, data sourced from the clinicaltrials.gov site