Table 2.
Selected phase I and II clinical trials of HDAC inhibitors in AML
| Study | Design | Participants | N | Responses | Median OS | Ref |
|---|---|---|---|---|---|---|
| Vorinostat | Single arm phase I | Relapsed or refractory leukemia, and MDS |
41 (31 of AML) | 17 % (2CR, 2CRi, 3 HI) | Not reported | 56 |
| Vorinostat (NCT00305773) |
Two-stage, randomized phase II |
Relapsed AML or untreated AML with age >65, antecedent MDS, poor cytogenetics |
37 (15 pts in arm A, 22 pts in arm B, arm A and arm B have different administration schedule) |
0% (arm A), 4.5% (CR) (arm B) |
105 days (arm A), 153 days (arm B) |
57 |
| Romidepsin (Depsipeptide) |
Two cohort, single arm phase II |
Second relapsed AML <60 years, first relapsed AML >60 years, previously untreated AML>60 years who are not candidates for or who refuse conventional chemotherapy |
20 (Cohort A: absence of chromosomal aberrations, Cohort B: presence of chromosomal aberrations (t(8;21), inv(16), t(15;17) |
Cohort A: 0%, Cohort B: no objective responses by criteria, yet 75% >50% decrease in BM blasts, and HI in 3 out of 7 patients. |
Not reported | 58 |
| VPA monotherapy or in combination with ATRA |
Single arm phase II | AML/MDS, AML/MPN, de novo AML |
75 (32 of AML) | 16% (3% CR, 13% HI) | Not reported | 59 |
| MGCD0103 (Mocetinostat) |
Single arm phase I | Relapsed or refractory AML, untreated AML with age >60 |
29 (22 of AML) | 2 complete BM response (blasts<5%) |
Not reported | 63 |
| MS-275 (Entinostat) |
Single arm phase I | Relapsed AML or untreated AML with age >65, antecedent MDS, poor risk features (complex karyotype, antecedent hematologic disease) |
38 | No CR/PR. 12 pts in BM response, decreased transfusion requirement, ANC improvement etc. |
Not reported | 64 |
| LBH589 (Panobinostat) |
Single arm phase I | Relapsed or refractory AML | 15 (13 of AML) | 8 out of 11 pts with peripheral blasts showed transient reduction. |
Not reported | 65 |
Pts: patients
CR (complete remission): the disappearance of all signs and symptoms related to the disease, a bone marrow with 5% or fewer blasts and peripheral blood count with an absolute neutrophil count of 109/L or more and platelet count of 100 × 109/L or more.
CRp: CR except for a platelet count increase by 50% to more than 30 × 109/L but less than 100 × 109/L.
PR (Partial remission): A cellular marrow aspirate with 5% to 25% blasts, with a platelet count greater than 100×109/L and WBC less than 1.5×109/L
Bone marrow (BM) response: bone marrow blast of 5% or less but without meeting the peripheral blood count criteria for CR or CRp.
Hematologic improvement (HI): HI-E: a hemoglobin increase by at least 15g/L or transfusion independence, HI-P: an absolute increase of platelet counts from less than 20 to more than 20 × 109/L and by at least 100% or if more than 20 × 109/L, by an absolute increase of at least 30 × 109/L, HI-N: a granulocyte increase by at least 100% and by an absolute increase of at least 0.5 × 109/L.
CCR: conventional care regimen
N: number of patients
Aza: azacitidine