Table 1.
Selected agents in clinical trials for the treatment of older adults with AML.
| Agent (Developing company) |
Structure | Development status | Cellular target/mechanism | ClinicalTrials.gov identifier |
|---|---|---|---|---|
|
| ||||
| CPX-351 (Celator Pharmaceuticals Inc) |
|
Phase II | 5:1 molar ratio of cytarabine:daunorubicin Cytarabine competes with cytidine for incorporation into DNA (inhibiting DNA synthesis) and also inhibits DNA polymerase (resulting in a decrease in DNA replication and repair). Daunorubicin, an intercalator and a topoisomerase II inhibitor (prevents DNA replication and inhibits protein synthesis) and generates oxygen free radicals, resulting in the cytotoxic lipid peroxidation of cell membrane lipids. |
NCT00788892 |
|
| ||||
| Alvocidib (sanofi-aventis/NCI) |
|
Phase II | CDK inhibitor that inhibits cell cycle progression and transcription. | NCT00407966 |
|
| ||||
| Clofarabine |
|
Launched | A purine nucleoside analog that inhibits DNA synthesis by two mechanisms: inhibition of DNA polymerase α and ribonucleotide reductase (ie, inhibits the repair of DNA damage). | NCT00373529 |
| NCT01041703 | ||||
|
| ||||
| Tipifarnib (Johnson & Johnson Pharmaceuti al Research and Development LLC) |
|
Phase II | Inhibits farnesyltransferase, resulting in the inhibition of multiple proteins involved in signaling, transcription and the cytoskeleton. | NCT00602771 |
|
| ||||
| Azacitidine |
|
Launched | Inhibits DNMT-1, resulting in the inhibition of gene- promoter region hypermethylation and subsequently reinstates gene expression. | NCT00313586 |
|
| ||||
| Decitabine |
|
Launched | Inhibits DNMT-1, resulting in the inhibition of gene- promoter region hypermethylation and subsequently reinstates gene expression. | NCT00313586 |
|
| ||||
| Laromustine (Vion Pharmaceutials Inc) |
|
Phase III | A sulfonylhydrazine alkylating agent that causes DNA crosslinking and strand breaks, chromosomal aberrations, disruption of DNA synthesis, and inhibition of the DNA repair enzyme 06- alkylguanine-DNA alkyl transferase. | NCT00354276 |
| NCT00655395 | ||||
|
| ||||
| Voreloxin (Sunesis Pharmaceuticals Inc) |
|
Phase II | A quinolone derivate that causes DNA intercalation and topoisomerase II inhibition, resulting in replication-dependent DNA damage, irreversible G2 arrest and subsequently apoptosis. | NCT00607997 |
|
| ||||
| Gemtuzumab |
|
Launched | Humanized mAb to CD33 linked to the cytotoxic agent N-acetyl-γ calicheamicin 1,2- dimethyl hydrazine dichloride. a antitumor antibiotics that associates with the minor groove of DNA and, following reduction with glutathione causes sequence-specific, double-stranded DNA cleavage. | NCT00927498 |
| NCT00091234 | ||||
| NCT00006122 | ||||
DNMT-1 DNA methyltransferase