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Table 1 Completed clinical trials of targeted therapies in T cell lymphomas

From: Novel targeted therapies of 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 -
   Relapsed or refractory MF/SS 5% 21.7 days NCT01728805
Belinostat Class I, II, and IV HDAC PTCL/CTCL PTCL 25%, CTCL 14% Nausea, vomiting, infusion site pain, and dizziness CTCL 83 days, PTCL 109 days NCT00274651
   Relapsed or refractory PTCL 25.80% Anemia, thrombocytopenia, dyspnea, and neutropenia 13.6 months -
Romidepsin Class I HDAC CTCL 34% Fatigue, nausea, vomiting, asthenic conditions, diarrhea, headache, ageusia, thrombocytopenia, dysgeusia, and granulocytopenia 13.7 months NCT00020436
   Refractory CTCL 34% 15 months NCT00106431
   CTCL/ PTCL 38% 8.9 months NCT00007345
   Tumor stage and folliculotropic MF Cutaneous MF 45%,folliculotropic MF 60% 15 months NCT00106431
   Relapsed or refractory PTCL/ CTCL Relapsed PTCL 33% Hematological toxicity and infections 13.5 months -
    Refractory PTCL 12.5%    
    Relapsed CTCL 25%    
    Refractory CTCL 0%    
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
     Non-T cell lymphoma 10%   
     T cell lymphoma 73%   
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
    PTCL 27%   PTCL 4.2 months  
Panobinostat HDAC MF/SS 17.30% Thrombocytopenia, diarrhea, fatigue, and nausea 5.6 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 9.9 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 550 days NCT00807495
   Relapsed/refractory PTCL or tMF PTCL 30% Fatigue, neutropenia, anemia, and thrombocytopenia 3 months NCT01466881
    tMF 0%    
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 13.8 months NCT02593045
Daratumumab CD38 Relapsed or refractory NK/T cell lymphomas 25% Pyrexia, headache, thrombocytopenia, anemia, leukopenia, and neutropenia 55 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 -
   MF/ SS 55% Fever, rigors, nausea, hypotension, anemia, neutropenia, thrombocytopenia, 12 months -
     CMV reactivation, fatal Mycobacterium pneumonia, and adverse cardiac events   
Alemtuzumab + chemotherapy CD52+cancer cells PTCL 72% Infections, leukocytopenia, thrombocytopenia, anemia No data available -
   CD52 + aggressive T/ NK lymphomas 83.30%   No data available
   Aggressive TCL 55.60%   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 -
   Relapsed/refractory PTCL/ CTCL 45.70% Fatigue, transaminase elevations PTCL 6.5 months NCT02567656
      CTCL 3.8 months  
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
   ALCL 53% Diarrhea, vision disorder, nausea, vomiting, elevated transaminases, neutropenia, leukopenia 2.6 years NCT01121588
  1. ORR—overall response rate; DOR—duration of response; HDAC—histone deacetylase; CTCL—cutaneous T cell lymphoma; MF—mycosis fungoides; tMF—transformed mycosis fungoides; SS—Sezary syndrome; PTCL—peripheral T cell lymphoma; TCL—T cell lymphoma; ICE—ifosfamide, carboplatin, etoposide; AZA—5-azacytidine; DLBCL—diffuse large B cell lymphoma; T-LBL/ALL—T cell acute lymphoblastic lymphoma/leukemia; CMV—cytomegalovirus; AAK—aurora A kinase; CHP—versus cyclophosphamide, doxorubicin, and prednisone; CART—chimeric antigen receptor T cell; PI3K—phosphoinositide-3-kinases; ALK- anaplastic lymphoma kinase; TSEBT—total skin electron irradiation, DHFR—dihydrofolate reductase