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Table 1 Clinical update of DNMT inhibitors

From: Recent developments in epigenetic cancer therapeutics: clinical advancement and emerging trends

Drug

Clinical studies

5-Azacytidine

Azacytidine is undergoing the below mentioned studies:

Low-risk MDS (Phase III, NCT01566695, status—active, not recruiting)

R/R T-cell lymphoma (Phase III, NCT03703375, status, recruiting)

AML with complete remission (Phase III, NCT01757535, active, not recruiting)

MDS patients with excess blasts, progressing (Azacitidine + rigosertib, Phase III, NCT01928537, status—active, not recruiting)

AML, MDS, CML (Azacitidine + HAG regimen, Phase III, NCT03873311, not yet recruiting)

AML (Azacitidine + venetoclax, NCT02993523, Phase III, status—recruiting)

MDS (Azacitidine + APR-246, NCT03745716, Phase III, status—recruiting)

AML, MDS, CML (Azacitidine + pevonedistat, Phase III, NCT03268954, status—recruiting)

AML with IDH1 mutation (Azacitidine + AG-120, Phase III, NCT03173248, status—recruiting)

AML (Azacitidine vs fludarabine + cytarabine, phase III, NCT02319135, status—active, not recruiting)

AML (Azacitidine + intensive chemotherapy, phase III, NCT03416179, status—recruiting)

Head and neck squamous cell carcinoma (Phase II, NCT02178072, status—recruiting)

Pancreatic cancer (Phase II, NCT01845805, status—recruiting)

Solid tumors and hematological disorders (Phase II, NCT02494258, status—recruiting)

AML (Azacitidine + venetoclax, Phase II, NCT03466294, NCT03573024, status—recruiting)

MDS, CMML and AML relapsing after allo-HSCT (Azacitidine + lenalidomide + DLI 50, Phase II, NCT02472691, status—active, not recruiting)

MDS with excess blasts 2 (Azacitidine + vosaroxin, Phase II, NCT03338348, status—ecruiting)

Advanced solid tumors (Azacitidine + durvalumab, Phase II, NCT02811497, status—recruiting)

High-risk MDS, AML (Azacitidine + durvalumab, NCT02775903, Phase II, status—active, not recruiting)

AML with NPM1 mutation (Azacitidine + pembrolizumab, Phase II, NCT03769532, status—not yet recruiting)

Pancreatic cancer (Azacitidine + pembrolizumab, NCT03264404, Phase II, status—recruiting)

Metastatic melanoma (Azacitidine + pembrolizumab, Phase II, NCT02816021, status—recruiting)

MDS (Azacitidine + pembrolizumab, Phase II, NCT03094637, status—recruiting)

Chemorefractory metastatic colorectal cancer (Azacitidine + pembrolizumab, Phase II, NCT02260440, status—active, not recruiting)

Advanced or metastatic non-small-cell lung cancer (Azacitidine + pembrolizumab, Phase II, NCT02546986, status—active, not recruiting)

Platinum-resistant ovarian cancer (Azacitidine + pembrolizuma, Phase II, NCT02900560, status—recruiting)

Prostate cancer (Azacitidine + ATRA, Phase II, NCT03572387, status—recruiting)

Recurrent or refractory disease with IDH2 mutation (Azacitidine + enasidenib, Phase II, NCT03683433, status—recruiting)

High-risk MDS with IDH2 mutation (Azacitidine + enasidenib, Phase II, NCT03383575, status—recruiting)

R/R AML (Azacitidine + pevonedistat, Phase II, NCT03745352, status—not yet recruiting)

High-risk MDS, AML, CML (Azacitidine + pevonedistat, Phase II, NCT02610777, status—active, not recruiting)

AML without remission after allogeneic stem cell transplantation (Azacitidine + pevonedistat, Phase II, NCT03709576, status—recruiting)

MDS, AML and CMML (Azacitidine + PF-04449913, Phase II, NCT02367456, status—recruiting)

PTCL (Azacitidine + CHOP, phase II, NCT03542266, status—recruiting)

Advanced non-small-cell lung cancer (Azacitidine + paclitaxel, phase II, NCT02250326, status—active, not recruiting)

MDS (Azacitidine + pevonedistat, Phase II, NCT03238248, status—recruiting)

Elderly patients with AML (Azacitidine + gemtuzumab ozogamicin, Phase II, NCT00658814, status—active, not recruiting)

Refractory/relapsed AML (Azacitidine + ipilimumab + nivolumab, Phase II, NCT02397720, status—recruiting)

MDS (Azacitidine + nivolumab + ipilimumab, Phase II, NCT02530463, status—recruiting)

High-risk MDS, AML (Azacitidine + sirolimus, Phase II, NCT01869114, status—recruiting)

R/R diffuse large B-cell lymphoma (Azacitidine + rituximab, Phase II, NCT03719989, status—not yet recruiting)

R/R AML (Azacitidine + avelumab, Phase I/II, NCT02953561, status—recruiting)

R/R AML, MDS (Azacitidine + quizartinib, phase I/II, NCT01892371, status—recruiting)

AML, high-risk MDS (Azacitidine + cytarabine + tosedostat, phase I/II, NCT01636609, status—active, not recruiting)

MDS (Azacitidine + sonidegib, Phase I, NCT02129101, status—active, not recruiting)

Decitabine (5-aza-2′deoxycytidine)-based trials

Decitabine is undergoing the below mentioned studies

 

R/R diffuse large B-cell lymphoma (Phase IV, NCT03579082, status—recruiting)

 

R/R T lymphoblastic lymphoma (Decitabine, Phase IV, NCT03558412, status—recruiting)

 

PTCL (Decitabine + CHOP, Phase III, NCT03553537, status—not yet recruiting)

 

AML with TP53 mutation (Decitabine, phase II, NCT03063203, status—recruiting)

 

AML (Decitabine + clofarabine, Phase II, NCT02085408, active, status—not recruiting)

 

AML (Decitabine + bortezomib, phase II, NCT01420926, status—active, not recruiting)

 

AML (Decitabine + cytarabine + daunorubicin hydrochloride, Phase II, NCT01627041, status—active, not recruiting)

 

Relapsed FLT3-ITD-mutated AML, MDS (Decitabine + quizartinib, Phase I/II, NCT03661307, status—recruiting)

 

AML (Decitabine + ruxolitinib, Phosphate, Phase I/II, NCT02257138, status—recruiting)

 

Metastatic castration-resistant prostate cancer (Decitabine + enzalutamide, Phase I/II, NCT03709550, status—not yet recruiting)

Guadecitabine (SGI-110)-based trials

Guadecitabine is currently being assessed in ASTRAL-2 (Phase III, R/R AML, NCT02920008) and ASTRAL-3 (phase III, MDSs (MDS) or chronic myelomonocytic leukemia, NCT02907359)

 

Guadecitabine is undergoing the below mentioned studies: MDS, CMML (Guadecitabine, NCT02907359, Phase III, status—recruiting)

 

Philadelphia-negative MDS (Guadecitabine, Phase II, NCT03075826, status—recruiting)

 

High-risk MDS (Guadecitabine, NCT02131597, Phase II, status—recruiting)

 

MDS relapsing post AlloSCT (Guadecitabine + DLI, NCT02684162, Phase II, status—recruiting)

 

Pembrolizumab, Phase II, NCT02901899, status—recruiting)

 

Metastatic colorectal cancer (Guadecitabine + irinotecan, Phase II, NCT01896856, status—active, not recruiting)

 

Refractory or resistant urothelial carcinoma (Guadecitabine + atezolizumab, Phase II, NCT03179943, status—recruiting)

 

Refractory metastatic colorectal cancer (Guadecitabine + nivolumab, Phase I/II, NCT03576963, status—Not yet recruiting)

 

Recurrent ovarian, primary peritoneal, or fallopian tube cancer (Guadecitabine + )

 

Advanced kidney cancer (Guadecitabine + durvalumab, Phase I/II, NCT03308396, status—recruiting)

 

Advanced MDS CMML (Guadecitabine + atezolizumab, Phase I/II, NCT0293536 status—recruiting)

 

Recurrent ovarian, fallopian tube, or primary peritoneal cancer (Guadecitabine + CDX-1401 Vaccine + atezolizumab, Phase I/II, NCT03206047, status—recruiting)

 

AML, MDS (Guadecitabine + DLI, Phase I, NCT03454984, status—not yet recruiting)

Hydralazine-based trials

Hydralazine is undergoing the below mentioned studies:

Ovarian cancer (Hydralazine + valproate, Phase III, NCT00533299, status—N/A)

Cervical cancer (Hydralazine + valproate, Phase III, NCT00532818, status—N/A)

Recurrent-persistent (cervical cancer, Hydralazine + valproate, Phase III, NCT02446652, status—N/A)