Table 1 Completed clinical trials of targeted therapies in T cell lymphomas
Drug name | Drug target | TCL type | ORR | Side effects | DOR | NCT number |
|---|---|---|---|---|---|---|
Vorinostat | Class I and II HDAC | Refractory, advanced CTCL | 24 – 30% | Thrombocytopenia, anemia, dehydration, nausea/vomiting, hypotension, infection, sepsis, pulmonary embolism and deep venous thrombosis | 106 days | - |
|  |  | Progressive, or recurrent MF/SS | 29.70% |  ≥ 185 days | NCT00091559 | |
|  |  | Refractory CTCL | 24% | 83.3—105.7 days | - | |
| Â | Â | Relapsed or refractory MF/SS | 5% | 21.7Â days | NCT01728805 | |
Belinostat | Class I, II, and IV HDAC | PTCL/CTCL | PTCL 25%, CTCL 14% | Nausea, vomiting, infusion site pain, and dizziness | CTCL 83Â days, PTCL 109Â days | NCT00274651 |
| Â | Â | Relapsed or refractory PTCL | 25.80% | Anemia, thrombocytopenia, dyspnea, and neutropenia | 13.6Â months | - |
Romidepsin | Class I HDAC | CTCL | 34% | Fatigue, nausea, vomiting, asthenic conditions, diarrhea, headache, ageusia, thrombocytopenia, dysgeusia, and granulocytopenia | 13.7Â months | NCT00020436 |
| Â | Â | Refractory CTCL | 34% | 15Â months | NCT00106431 | |
| Â | Â | CTCL/ PTCL | 38% | 8.9Â months | NCT00007345 | |
| Â | Â | Tumor stage and folliculotropic MF | Cutaneous MF 45%,folliculotropic MF 60% | 15Â months | NCT00106431 | |
| Â | Â | Relapsed or refractory PTCL/ CTCL | Relapsed PTCL 33% | Hematological toxicity and infections | 13.5Â months | - |
| Â | Â | Â | Refractory PTCL 12.5% | Â | Â | Â |
| Â | Â | Â | Relapsed CTCL 25% | Â | Â | Â |
| Â | Â | Â | Refractory CTCL 0% | Â | Â | Â |
Romidepsin + TSEBT | Class I HDAC + skin irradiation | Advanced-stage MF/SS | No data available | Nausea, fatigue, loss of appetite, erythema, and desquamation | 2-28 months | - |
Romidepsin + bendamustine | Class I HDAC + DNA | Relapsed/ refractory PTCL | No data available | Nausea, vomiting in most patients, thrombocytopenia, and neutropenia | 9 months | - |
Romidepsin + ICE | Class I HDAC +  cancer cells | Relapsed or refractory PTCL | 93% | No data available | 15 months | NTC01590732 |
Romidepsin + pralatrexate | Class I HDAC + DHFR | Relapsed/refractory lymphomas | All lymphomas 57%, PTCL 71% | Nausea, fatigue, anorexia, diarrhea, and fever | 4.29 months | NCT01947140 |
Romidepsin + AZA | Class I HDAC + DNA methylation | Non-T cell/T cell lymphomas | All lymphomas 32% | Thrombocytopenia, neutropenia, and pleural effusion | 1.8 – 16.3 + months | NCT01998035 |
| Â | Â | Â | Â | Non-T cell lymphoma 10% | Â | Â |
| Â | Â | Â | Â | T cell lymphoma 73% | Â | Â |
Romidepsin + alisertib | Class I HDAC + AAK | Relapsed/refractory aggressive B cell and T cell lymphomas | 28% | Fatigue, nausea, infection, neutropenia, anemia, and thrombocytopenia | No data available | NCT0189701 |
Romidepsin + lenalidomide | Class I HDAC + E3 ubiquitin ligase | PTCL/ CTCL | 53% | Neutropenia, thrombocytopenia, anemia, electrolyte abnormalities | No data available | NCT01755975 |
Romidepsin + liposomal doxorubicin | Class I HDAC + DNA | Relapsed/refractory CTCL and PTCL | CTCL 70% | Thrombocytopenia, anemia, neutropenia, fatigue, nausea, vomiting, and anorexia | CTCL 5.1 months | NCT01902225 |
| Â | Â | Â | PTCL 27% | Â | PTCL 4.2 months | Â |
Panobinostat | HDAC | MF/SS | 17.30% | Thrombocytopenia, diarrhea, fatigue, and nausea | 5.6Â months | NCT00425555 |
|  |  | Various hematologic malignancies | No data available | Thrombocytopenia fatigue, neutropenia | MF 1–369 days | - |
Chidamide | HDAC 1,2,3, and 10 | Relapsed or refractory PTCL | 28% | Thrombocytopenia, leucopenia, and neutropenia | 9.9Â months | - |
Chidamide + chemotherapy | HDAC 1,2,3 and 10 + cancer cells | Refractory or relapsed T-LBL/ALL | 71% | Febrile neutropenia, drug-induced liver failure, decreased fibrinogen, sepsis, pneumonitis, and oral mucositis | 9.4 months | - |
|  |  | Relapsed or refractory PTCL | Chidamide 39.06%, chidamide + chemotherapy 51.18% | Thrombocytopenia, neutropenia, anemia, and fatigue | Chidamide 148 days, chidamide + chemotherapy 169 days | - |
Alisertib | AAK | Relapsed/refractory aggressive NHL | 27% | Neutropenia, leukopenia, anemia, thrombocytopenia, stomatitis, and fatigue | 550Â days | NCT00807495 |
| Â | Â | Relapsed/refractory PTCL or tMF | PTCL 30% | Fatigue, neutropenia, anemia, and thrombocytopenia | 3Â months | NCT01466881 |
| Â | Â | Â | tMF 0% | Â | Â | Â |
Brentuximab vedotin + CHP | CD30 + cancer cells | CD30 + patients with PTCL | 95% | Febrile neutropenia, peripheral neuropathy | No data available | NCT01777152 |
IPH4102 | KIR3DL2 | Refractory CTCL | 36.40% | Peripheral edema and fatigue | 13.8Â months | NCT02593045 |
Daratumumab | CD38 | Relapsed or refractory NK/T cell lymphomas | 25% | Pyrexia, headache, thrombocytopenia, anemia, leukopenia, and neutropenia | 55Â days | NCT02927925 |
TTI-621 | CD47 | Relapsed or refractory SS/ MF | No data available | Fatigue, chills, and decreased appetite | No data available | NCT02890368 |
Alemtuzumab | CD52 | Pretreated and refractory PTCL | 36% | Shivers, chills, significant hematologic toxicity, and CMV reactivation | 2–12 months | - |
| Â | Â | MF/ SS | 55% | Fever, rigors, nausea, hypotension, anemia, neutropenia, thrombocytopenia, | 12Â months | - |
| Â | Â | Â | Â | CMV reactivation, fatal Mycobacterium pneumonia, and adverse cardiac events | Â | Â |
Alemtuzumab + chemotherapy | CD52+cancer cells | PTCL | 72% | Infections, leukocytopenia, thrombocytopenia, anemia | No data available | - |
|  |  | CD52 + aggressive T/ NK lymphomas | 83.30% |  | No data available | - |
| Â | Â | Aggressive TCL | 55.60% | Â | No data available | NCT00562068 |
AFM13 | CD30/ CD16A | Relapsed or refractory CD30 + CTCL | 50% | Infusion-related reaction, cellulitis, | No data available | NCT03192202 |
E777 | IL-2 receptor | Relapsed or refractory PTCL/ CTCL | 38% | Lymphopenia, thrombocytopenia, leukocytosis, anemia, neutropenia, decreased appetite, fatigue, hypoalbuminemia, and nausea | No data available | NCT1401530 |
Duvelisib | PI3K-δ/-γ | Relapsed or refractory PTCL/ CTCL | PTCL 50.0% | Transaminase increases, maculopapular rash, and neutropenia | PTCL 1.8–17.3 months | NCT01476657 |
|  |  |  | CTCL 31.6%, |  | CTCL 0.7–10.1 months |  |
Tenalisib | PI3K-δ/-γ | Relapsed/refractory hematologic malignancies | 19% | Asthenia, cough, pyrexia, diarrhea, nausea, vomiting, hypertriglyceridemia, and neutropenia | 5.7 months | - |
| Â | Â | Relapsed/refractory PTCL/ CTCL | 45.70% | Fatigue, transaminase elevations | PTCL 6.5Â months | NCT02567656 |
| Â | Â | Â | Â | Â | CTCL 3.8Â months | Â |
Crizotinib | ALK | Relapsed/refractory ALCL | ALCL 83%—90% | Neutrophil count decrease | No data available | NCT00939770 |
Ceritinib | ALK | ALCL | No data available | Diarrhea, abdominal discomfort, vomiting, fatigue, increase in transaminase levels, acute pericarditis |  ≥ 20 months | NCT01283516 |
| Â | Â | ALCL | 53% | Diarrhea, vision disorder, nausea, vomiting, elevated transaminases, neutropenia, leukopenia | 2.6Â years | NCT01121588 |