Table 2 Epitherapy in clinical trials for cancer and CVDs

Drugs in clinical trial

SGI-110 (guadecitabine)

AML

302 participants,

Interventional,

Randomized,

Parallel Assignment,

Treatment

Phase 3 Randomized, Open-Label Study of Guadecitabine vs Treatment Choice in Previously Treated Acute Myeloid Leukemia

Multicenter, randomized, open-label, parallel-group study of guadecitabine vs treatment choice

Active/Phase 3

NCT02920008

MDS

CMML

408 participants,

Interventional,

Randomized,

Parallel Assignment,

Treatment

Guadecitabine (SGI-110) vs Treatment Choice in Adults With MDS or CMML Previously Treated With HMAs

To evaluate the efficacy and safety of guadecitabine in MDS or CMML who failed or relapsed after treatment with azacitidine, decitabine, or both

Active/Phase 3

NCT02907359

AML

815 participants,

Interventional,

Randomized,

Parallel Assignment,

Treatment

SGI-110 in Adults With Untreated Acute Myeloid Leukemia (AML), Not Considered Candidates for Intensive Remission Induction

To compare efficacy and safety between SGI-110 and treatment in adults with previously untreated AML

Completed/

Phase 3

NCT02348489

RX-3117

MPC

46 participants,

Interventional,

N/A,

Single group Assignment,

Treatment

RX-3117 in Combination With Abraxane® in Subjects With Metastatic Pancreatic Cancer

To determine the safety profile, dose modification, and pharmacokinetics of oral RX-3117 administered in combination with Abraxane® to subjects with metastatic pancreatic cancer

Completed/

Phase 1/2

NCT03189914

Solid tumor

Metastatic Bladder Cancer

124 participants,

Interventional,

N/A,

Single group Assignment,

Treatment

Dose-Finding and Safety Study for Oral Single-Agent to Treat Advanced Malignancies

To determine the maximum tolerated dose in metastatic solid tumors and to estimate anti-tumor activity in subjects with relapsed or refractory pancreatic or advanced bladder cancer

Completed/

Phase 1/2

NCT02030067

INCB059872

Solid tumors

Advanced Malignancies

Metastatic Cancer

70 participants,

Interventional,

N/A,

Single group Assignment,

Treatment

Azacitidine Combined With Pembrolizumab and Epacadostat in Subjects With Advanced Solid Tumors (ECHO-206)

To evaluate the safety and tolerability of INCB059872 with pembrolizumab and epacadostat

Completed

Phase 1/2

NCT02959437

Solid tumors and hematologic malignancy

215 participants,

Interventional,

N/A,

Single group Assignment,

Treatment

An Open-Label, Dose-Escalation/Dose-Expansion Safety Study of INCB059872 in Subjects With Advanced Malignancies

To determine the safety, tolerability, efficacy, PK, PD, and the recommended dose(s) of azacitadine and all-trans retinoic acid in AML and in combination with nivolumab in SCLC

Recruiting

Phase 1/2

NCT02712905

CI-994

MM

6 participants,

Interventional,

N/A,

Single group Assignment,

Treatment

CI-994 in Treating Patients With Advanced Myeloma

To study the effectiveness of CI-994 in treating patients who have advanced myeloma

Completed

Phase 2

NCT00005624

Lung cancer

Interventional,

Randomized,

Treatment

Gemcitabine With or Without CI-994 in Treating Patients With Advanced Non-small Cell Lung Cancer

To compare the effectiveness of gemcitabine with or without CI-994 in treating patients who have advanced non-small cell lung cancer

Completed

Phase 3

NCT00005093

Pancreatic cancer

Interventional,

Randomized,

Treatment

Gemcitabine With or Without CI-994 in Treating Patients With Advanced Pancreatic Cancer

To compare the effectiveness of gemcitabine with or without CI-994 in treating patients who have advanced pancreatic cancer

Completed

Phase 2

NCT00004861

EPZ-5676

(Pinometostat)

AML with 11q23 rearrangement

36 participants,

Interventional,

N/A,

Single group Assignment,

Treatment

Pinometostat and Azacitidine in Treating Patients With Relapsed, Refractory, or Newly Diagnosed Acute Myeloid Leukemia With 11q23 Rearrangement

To study the side effects and the dose of pinometostat with azacitidine in AML with 11q23 rearrangement

Recruiting

Phase 1/2

NCT03701295

AML with 11q23 rearrangement

37 participants,

Interventional,

N/A,

Single group Assignment,

Treatment

Pinometostat With Standard Chemotherapy in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia and MLL Gene Rearrangement

To study the side effects and the dose of pinometostat in AML with 11q23 rearrangement

Recruiting

Phase 1/2

NCT03724084

TCP

AML

16 participants,

Interventional,

N/A,

Single group Assignment,

Treatment

Phase I/II Trial of ATRA and TCP in Patients With Relapsed or Refractory AML and no Intensive Treatment is Possible

To study the feasibility, pharmacodynamics, and effectivity of ATRA and TCP in AML

Phase 1/2

NCT02261779

AML,

MDS

60 participants,

Interventional,

N/A,

Single group Assignment,

Treatment

Study of Sensitization of Non-M3 AML Blasts to ATRA by Epigenetic Treatment With Tranylcypromine (TCP)

To study the maximum tolerated and the efficacy dose of TCP with ATRA and Cytarabine

Recruiting

Phase 1/2

NCT02717884

CPI-0610

Myelofibrosis

AML,

MDS/MPD,

MDS

271 participants,

Interventional,

Non-Randomized,

Parallel Assignment,

Treatment

A Phase 2 Study of CPI-0610 With and Without Ruxolitinib in Patients With Myelofibrosis

Open-label, sequential dose escalation study of CPI-0610 and open-label study of CPI-0610 with and without Ruxolitinib in patients with Myelofibrosis

Recruiting

Phase 1/2

NCT02158858

Rocilinostat (ACY-1215)

MM

101 participants,

Interventional,

Single Group Assignment,

Treatment

ACY-1215 (Ricolinostat) in Combination With Pomalidomide and Low-dose Dex in Relapsed-and-Refractory Multiple Myeloma

To evaluate the side effects, determine the best dose and the response rate of ACY-1215 in combination with Pomalidomide and low-dose dexamethasone in patients with relapsed-and-refractory multiple myeloma

Active, not recruiting

Phase 1b/2

NCT01997840

Mocetinostat

Urothelial carcinoma

17 participants,

Interventional,

N/A,

Single group Assignment,

Treatment

Study of Mocetinostat in Patients With Urothelial Carcinoma Having Inactivating Alterations of Specific Genes

To evaluate whether the number of patients responding to treatment is substantially higher than other available treatments

Completed/ Phase II

NCT02236195

Hodgkin’s lymphoma

51 participants,

Interventional,

Non-Randomized,

Single group Assignment,

Treatment

Study of MGCD0103 (MG-0103) in Patients With Relapsed or Refractory Hodgkin’s Lymphoma

To study the effect of Mocetinostat on patients with relapsed and refractory Hodgkin’s lymphoma

Terminated/ Phase II

NCT00358982

CPI-1205

mCRPC

242 participants,

Interventional,

Randomized,

Parallel Assignment,

Treatment

ProSTAR: A Study Evaluating CPI-1205 in Patients With Metastatic Castration Resistant Prostate Cancer

To study the oral administration of CPI-1205 in combination with enzalutamide or abiraterone/prednisone in male patients with mCRPC

Active, not recruiting/ Phase I/II

NCT03480646

Advanced Solid Tumors

24 participants,

Interventional,

N/A,

Single group Assignment,

Treatment

ORIOn-E: A Study Evaluating CPI-1205 in Patients With Advanced Solid Tumors

To determine the maximum tolerated dose and recommended phase 2 dose of CPI-1205 + ipilimumab in patients with advanced solid tumors

Active, not recruiting/ Phase I/II

NCT03525795

Approved epi-drug ongoing in clinical trial for other treatments

Vorinostat

ALL, LLy

1000 participants,

Interventional,

Randomized,

Parallel Assignment,

Treatment

Total Therapy XVII for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia and Lymphoma

To study a novel strategies based on inherited and acquired leukemia-specific genomic features and treatment to improve the cure rate and quality of life of ALL and LLy children

Recruiting/

Phase2/3

NCT03117751

MM

637 participants,

Interventional,

Randomized,

Single group Assignment,

Treatment

Study of Vorinostat (MK-0683) an HDAC Inhibitor, or Placebo in Combination with Bortezomib in Patients With Multiple Myeloma (MK-0683-088 AMN)

To study of the efficacy and safety of bortezomib administered in combination with vorinostat in patients with relapsed or refractory MM

Complete/

Phase 3

NCT00773747

MLC

662 participants,

Interventional,

Randomized,

Single group Assignment,

Treatment

Suberoylanilide Hydroxamic Acid (Vorinostat, MK-0683) Versus Placebo in Advanced Malignant Pleural Mesothelioma (0683-014 AM5, EXT1)

To study the safety, tolerability, and anti-tumor effectiveness of vorinostat in oral administration, for MLC

Complete/

Phase 3

NCT00128102

Panobinostat

AML, MDS

350 participants,

Interventional,

Randomized,

Parallel Assignment

Treatment

Panobinostat Maintenance After HSCT for High-risk AML and MDS

To compare maintenance treatment with panobinostat versus the standard approach of preemptive DLI alone in patients with poor-risk AML/MDS

Recruiting/

Phase 3

NCT04326764

PMF, CIM, post-PVMF, PET-MF, SR-GVHD

356 participants,

Interventional,

Non-Randomized,

Parallel Assignment

Treatment

CINC424A2X01B Rollover Protocol

To study the efficacy of ruxolitinib and panobinostat in combination for patients that use the study treatment based on the parent protocol

Recruiting/ Phase 4

NCT02386800

Vidaza

AML

488 participants,

Interventional,

Randomized,

Parallel Assignment,

Treatment

Study of Vidaza Versus Conventional Care Regimens for the Treatment of Acute Myeloid Leukemia (AML)

To compare the effect of azacitidine to conventional care regimens in AML patients

Complete/

Phase 3

NCT01074047

AML

47 participants,

Interventional,

Non-Randomized,

Parallel Assignment,

Treatment

zacitidine Combined With Homoharringtonie in AML

To validate the efficacy and safety advantages of the regimens that contain homoharringtonie and azacitidine, and to determine which regimen would receive more living benefits in AML

Recruiting/ Phase 3

NCT04248595

AML,

MDS,

CMML

187 participants,

Interventional,

Randomized,

Single group Assignment,

Treatment

Controlled Study of Post-transplant Azacitidine for Prevention of Acute Myelogenous Leukemia and Myelodysplastic Syndrome Relapse (VZ-AML-PI-0129)

To study if Vidaza will help to control the disease in patients with AML, CMML, or MDS after a stem cell transplant

Complete/

Phase 3

NCT00887068

AML,

MDS,

CML

114 participants,

Interventional,

Randomized,

Parallel Assignment,

Treatment

Azacytidine + HAG Regimen vs. Azacytidine for Elderly Patients With Newly Diagnosed Myeloid Malignancy

To explore the efficacy and safety of azacytidine and HAG regimen versus azacytidine for elderly patients with Newly Diagnosed MDS/AML/CMML in China

Recruiting/ Phase 4

NCT03873311

Decitabine

T-ALL, T-LBL, T/M-MPAL

100 participants,

Interventional,

N/A,

Single group Assignment

Treatment

Study of Decitabine Combined With HAAG Regimen in Newly Diagnosed ETP-ALL/LBL, T/M-MPAL and ALL/LBL With Myeloid or Stem Cell Markers Patients

To evaluate the efficacy and safety of decitabine combined with HAAG

Recruiting/ Phase 3

NCT04446130

DLBCL

60 participants,

Interventional,

Randomized,

Parallel Assignment Treatment

A Clinical Trial of Decitabine in Relapse and Refractory Diffuse Large B Cell Lymphoma

To evaluate the safety, tolerability, and clinical effects of decitabine with R ± DHAP

Recruiting/ Phase 4

NCT03579082

Tazametostat

Solid tumor

49 participants,

Interventional,

N/A,

Single group Assignment

Treatment

Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial)

To study the action of tazemetostat in patients with brain tumors, solid tumors, non-Hodgkin lymphoma, or histiocytic disorders that have come back (relapsed) or do not respond to treatment (refractory) and have EZH2, SMARCB1, or SMARCA4 gene mutations

Phase 2

NCT03213665

Drug repositioning in CVDs

Trimetazidine

HFpEF

25 participants,

Interventional,

Randomized,

Placebo-controlled

TrimetaziDine as a Performance-enhancING drug in Heart Failure with Preserved Ejection Fraction

To assess whether trimetazidine improves LV diastolic function by improving myocardial energy metabolism in HFpEF

Ongoing/

Phase 2

EU Clinical Trial Register: 2018-002170-52; NTR registration: NL7830

[van de Bovenkamp AA,

PAH

26 participants,

Interventional,

Randomized,

Placebo-controlled

The Role of Trimetazidine on Right Ventricle Function in Pulmonary Arterial Hypertension (TRIMETA-PH)

To evaluate the effect of trimetazidine versus placebo in addition to standard PAH regime on right ventricular function

Completed/Phase 2/ 3

NCT03273387

Tocilizumab

PAH

29 participants,

Interventional,

Single‐arm

A Therapeutic Open Label Study of Tocilizumab in the Treatment of Pulmonary Arterial Hypertension (TRANSFORM-UK)

To assess the safety and efficacy of tocilizumab in PAH

Completed/Phase 3

NCT02676947

Metformin

MetS

40 participants,

Interventional,

Randomized,

Placebo-controlled

Combination of Metformin/Inulin vs Inulin on Adiponectin in Metabolic Syndrome

To compare the effect of the administration of Metformin/agave inulin vs. Agave inulin on adiponectin in patients with MetS

Completed/

Phase 3

NCT02773927

T2D,

HF

30 participants,

Observational,

Cohort,

Prospective

Lipid Accumulation in Heart Transplant From Non-diabetic Donors to Diabetic Recipients (DCM-AHEAD)

To evaluate in the explanted diabetic heart the presence of possible cellular alterations attributable to the diabetic disease discerning from treated and non-treated with metformin

Completed/NA

NCT03546062

PAH

1899 participants,

Observational,

Cohort,

Prospective

Hormonal, Metabolic, and Signaling Interactions in PAH

To evaluate if an optimal treatment of the dysfunctional metabolic pathways underlying PAH may improve pulmonary vascular function and consequences of the disease

Recruiting/NA

NCT01884051

Apabetalone

(RVX 208)

PAH

10 participants,

Interventional,

Single‐arm,

2‐center study

Apabetalone for Pulmonary Arterial Hypertension: a Pilot Study

To evaluate the possible efficacy of apabetalone in treating PAH

Recruiting/Early Phase 1

NCT03655704

T2D-CHD

2425 participants, Interventional,

Randomized,

Placebo-controlled

Effect of RVX000222 on Time to Major Adverse Cardiovascular Events in High-Risk T2DM Subjects With CAD (BETonMACE)

To determine whether RVX000222 in high-risk type 2 diabetes mellitus patients with coronary artery disease increases the time to major adverse cardiovascular events

Phase 3/Active

NCT02586155

n-3 PUFA

or

Rosuvastatin

HF

6975 participants,

Interventional,

Randomized,

Placebo-controlled

GISSI-HF- Effects of n-3 PUFA and Rosuvastatin on Mortality-Morbidity of Patients With Symptomatic CHF

To demonstrate that, in HF patients treated at the best of recommended therapies, long-term administration of n-3 PUFA or rosuvastatin is more effective than the corresponding placebo

Completed/

Phase 3

NCT00336336

Tavazzi et al. [128]