Table 1. Completed clinical trials of proteasome inhibition in AML patients.
| Trial no. (Phase) | Patients (Median age)a | Intervention | Adverse eventsb | Responsec | Survival (Months)d |
|---|---|---|---|---|---|
| NCT00005064 (I) | 15 total, 11 r/r AML (59 years) | Bortezomib | Orthostatic hypotension Nausea Diarrhea | No CR/CRi Reduced blasts in 33% | N/R |
| EUDRACT 2006-006923-38 (II) | 14 new or r/r AML ineligible for conventional chemotherapy (70 years) | Bortezomib | Infection/FN Neuropathy | No CR/CRi Reduced blasts in 61% | 4 |
| NCT00382954 (I) | 20 new or r/r AML (65 years) | Bortezomib Idarubicin | Infection/FN Constitutional Gastrointestinal | 20% CR 5% PR Reduced blasts in 75% | 4 |
| NCT00624936 (I) | 23 r/r AML (65 years) | Bortezomib Azacitidine | Infection/FN Neuropathy Thrombocytopenia | 22% CR/CRi | N/R |
| NCT00703300 (I) | 19 poor-risk AML (70 years) | Bortezomib Decitabine | Infection/FN Neuropathy | 37% CR/CRi | N/R |
| NCT00818649 (II) | 12 total, 8 AML (65.5 years) | Bortezomib Vorinostat | Cardiac events Nausea Neuropathy | 8% CR | N/Re |
| NCT00505700 (I) | 31 new and r/r AML (62 years) | Bortezomib Idarubicin Cytarabine | Hypoxia Hyperbilirubinemia Elevate AST | 71% CR/CRi | 12 |
| NCT00742625 (II) | 95 untreated AML (67 years) | Bortezomib Daunorubicin Cytarabine | Infection/FN Neuropathy | 69% CR/CRi | 12 |
| NCT01174888 (I) | 23 r/r AML (53 years) | Bortezomib Midostaurin MEC | Neuropathy Decreased LVEF Diarrhea | 82.5% CR/CRi | 11 |
| NCT00666588 (II) | 37 r/r AML (8 years) | Bortezomib plus: Idarubicin/Cytarabine or Cytarabine/Etoposide | Infection/FN Hypokalemia Hypoxia | 57% CR/Cri or 48% CR/CRi | 39% at 2 years |
| NCT00666588 (I) | 23 total, 9 AML (73 years) | Bortezomib Lenalidomide | Infection/FN Neuropathy Hypoxia | 11% CR/CRi | 5 |
| NCT00103272 (I) | 11 r/r AML (63 years) | Bortezomib 17-AAGf | Infection/FN Hepatotoxicity Cardiotoxicity | No response | N/R |
a
R/r, relapsed/refractory.
b
FN, febrile neutropenia.
c
CR, complete remission, CRi, complete remission with incomplete recovery of platelets or neutrophils, PR, partial remission.
d
N/R, not reported.
e
No quantitative survival data was reported in this study, though all patients died of progressive disease within 1 year.
f
17-AAG, 17-allylamino-17-demethoxygeldanamycin.