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Table 4 Novel agents and combinations under investigation in PTCL

From: Biomarker-driven management strategies for peripheral T cell lymphoma

Setting Agent(s) Study Phase N Treatment ClinicalTrials.gov
Front-line Romidepsin + CHOEP Young patients with untreated nodal PTCL: a phase I–II study I/II 110 Phase I: romidepsin dose escalation + CHOEP-21, followed by stem cell mobilization and transplantation
Phase II: Ro-CHOEP-21 × 3 cycles; if PR or CR, Ro-CHOEP-21 continues for 3 additional cycles followed by stem cell mobilization and transplantation.
NCT02223208
Azacitadine (CC-486) + CHOP Previously untreated PTCL II 20 CC-486 priming is given from D-6 to D0 before cycle 1, and D8-D21 during
Cycles 1 to 5.
NCT03542266
Romidepsin + CHOP vs CHOP Patients with previously untreated PTCL III 421 Control Arm: CHOP 21 for 6 cycles
Experimental Arm: Ro-CHOP 21 with romidepsin 12 mg/m2 given IV on D1 and D8 Q3 weeks for 6 cycles
NCT01796002
Romidepsin + lenalidomide Phase II study of romidepsin plus lenalidomide for patients with previously untreated PTCL II 35 Romidepsin on D1, 8, and 15, and lenalidomide PO QD on D1-21, every 28 days for up to 1 year in the absence of POD or unacceptable toxicity NCT02232516
Relapsed/refractory Azacitadine vs. investigator’s choice Randomized phase 3 study for patients with R/R AITL III 86 Experimental arm: oral azacitadine 300 mg daily × 14 days of 28-day cycles (European patients)
Oral azacitadine 200 mg daily × 12 days of 28-day cyclesControl: romidepsin 14 mg/m2 on d1, 8, and 15 of 28-day cycle until POD, toxicity, or patient decision, or bendamustine 120 mg/m2 on d1 and 2 of a 21-day cycle (during 6 cycles); or gemcitabine 1200 mg/m2 on d1, 8, and 15 of a 28-day cycle (during 6 cycles)
NCT03593018
Pembrolizumab + romidepsin A phase I/II study of pembrolizumab (MK-3475) in combination with romidepsin in patients with R/R PTCL I/II 39 Romidepsin is given on D1 and D8. Pembrolizumab is given IV over 30 min on D1. Cycles repeat every 21 days for up to 36 cycles in the absence of POD or unacceptable toxicity. NCT03278782
Pembrolizumab + pralatrexate A phase 1/2 study of pembrolizumab plus pralatrexate for treatment of R/R PTCL I/II 40 Dose escalation of pralatrexate + pembrolizumab
Pralatrexate is given IV over 3–5 min on D1 and 8 and pembrolizumab is given IV over 30 min on D1, repeat every 21 days.
NCT03598998
Durvalumab ± lenalidomide A phase 1/2 trial of durvalumab given as a single agent or in combination with lenalidomide in patients with R/R PTCL, including CTCL I/II 62 Arm 1: patients receive durvalumab IV over 1 h on D1.Arm 2: durvalumab + lenalidomide
Patients receive durvalumab IV over 1 h on D1 and lenalidomide PO QD on D1-21.Treatment repeats every 28 days (± 3 days) for up to 13 courses in the absence of POD or unacceptable toxicity for both arms.
NCT03011814
Durvalumab ± pralatrexate, romidepson, azacitadine Phase 1/2a study in patients with R/R PTCL I/II 148 Arm A: durvalumab, 5-azacitadine (AZA)Arm B: durvalumab, pralatrexate, romidepsinArm C: durvalumab, romidepsinArm D: durvalumab, AZA NCT03161223
Pembrolizumab ± pralatrexate and decitabine Novel immuno-epigenetic-based platform for patients with PTCL and CTCL: an international phase Ib study of pembrolizumab combined with decitabine and pralatrexate Ib 42 Arm A: pembrolizumab + pralatrexate
Pembrolizumab 200 mg is given IV D1 1 with pralatrexate 30 mg/m2 IV D1, 8, and 15Arm B: pembrolizumab + pralatrexate + decitabine
Pembrolizumab 200 mg is given IV D8 with pralatrexate 20 mg/m2 IV D1, 8, and 15 and decitabine 10 mg/m2 from D1 to 5Arm C: pembrolizumab + decitabine
Pembrolizumab 200 mg is given IV and decitabine 20 mg/m2 from D1 to 5.
NCT03240211
AvelumabPD-1 mAb A phase 2a trial of avelumab, an anti-PDL1 antibody, in R/R PTCL II 35 Avelumab is given 10 mg/kg by IV infusion once every 2 weeks. A maximum of 8 cycles, each cycle is 28 days. NCT03046953
BGB-A317 (tislelizumab)PD-1 mAb A phase 2, open-label study of BGB-A317 in patients with R/R mature T- and NK-neoplasms II 90 BGB A317 is given 200 mg IV on D1 of each 21-day cycle. NCT03493451
Copanlisib + romidepsin Copanlisib in combination with romidepsin in patients with R/R mature TCL IB 30 Dose escalation of copanlisib in combination with romidepsin NCT04233697
YY-20394PI3K-δ inhibitor A single-arm, open-label, multi-center, phase I study of YY-20394 in patients with R/R PTCL I 58 YY-20394 tablets will be given daily for 28 days in 28-day cycles until POD, intolerable toxicity, or the subject discontinues from the study treatment for other reasons. NCT04108325
Pralatrexate + romidepsin Phase I/IIA study of the novel antifolate agent pralatrexate in combination with the histone deacetylase inhibitor romidepsin for the treatment of patients with PTCL I/II 93 Phase I: dose escalation of pralatrexate and romidepsin. Patients receive both infusions D1 and D15 of each 28-day cycle
Phase II: pralatrexate 25 mg/m2 and romidepsin 12 mg/m2 are given IV once weekly on D1 and 15 on a 28-day cycle
NCT01947140
DS-3201bEZH2 inhibitor A phase 1 multiple ascending dose study of DS-3201b in subjects with lymphomas I 70 Dose escalation of DS-3201b NCT02732275
IDH2 (AG-221) A phase 1/2, multicenter, open-label, dose-escalation study of AG-221 in subjects with advanced solid tumors, including glioma, and with AITL, that harbor an IDH2 mutation I/II 21 AG-221 administered orally on every day of 28-day cycles until POD or unacceptable toxicities. Multiple doses. NCT02273739
RuxolitinibJAK inhibitor A phase 2 multicenter, investigator initiated study of oral ruxolitinib phosphate for the treatment of R/R diffuse large B cell and PTCL II 71 Ruxolitinib is administered orally BID on D1–28 repeat courses Q 28 days in the absence of POD or unacceptable toxicity. NCT01431209
AZD4205JAK inhibitor A phase I/II, open-label, multicenter study to investigate the safety, tolerability, pharmacokinetics, and anti-tumor activity of AZD4205 in patients with PTCL I/II 100 AZD4205 will be administrated orally as capsules in 2 dose cohorts. AZD4205 treatment will be continued until disease progression or intolerable adverse reactions NCT04105010
CerdulatinibSYK/JAK inhibitor A phase 1/2A open-label, multi-dose, multi-center escalation and exploratory study of cerdulatinib (PRT062070) in patients with R/R CLL, SLL, or B cell or T cell NHL I/II 283 Phase I: Dose escalation or cerdulatiniib staring at 15 mg dailyPhase II: Cerdulatinib administered at 30 mg PO BID for 28-day cycles. Six planned cohorts, cohort 2 also received rituximab IV 375 mg/m2 NCT02273739
VenetoclaxBCL-2 inhibitor A phase II, open-label, multicenter trial of venetoclax (ABT-199/GDC-0199) as single agent in patients with R/R BCL-2 positive PTCL-NOS, AITL, and other nodal TCL of T-follicular helper origin (TFH) II 35 Venetoclax (ABT-199) 800 mg is administered orally daily until POD, unacceptable toxicity, withdrawal of consent and/or investigator’s decision NCT03552692
Tipifarnib An open-label phase II study of tipifarnib in subjects with relapsed or refractory peripheral T cell lymphoma II 30 Tipifarnib 300 mg is given orally twice daily on D1–21 of 28-day treatment cycles NCT02464228
MEDI-570 ICOS mAb A phase I trial of MEDI-570 in patients with R/R PTCL follicular variant and AITL I 46 Anti-ICOS monoclonal antibody MEDI-570 is given IV over 1–4 h on day 1. Treatment repeats every 21 days for up to 12 cycles in the absence of POD or unacceptable toxicity. NCT02520791
DaratumumabCD38 mAb A Phase II, open-label, multicenter trial of daratumumab in combination with gemcitabine, dexamethasone and cisplatin (D-GDP) in patients with R/R CD38-positive PTCL-NOS, AITL, and other nodal lymphomas of TFH cell origin II 35 Induction phase: 4–6 courses (according to response after cycle 4 and to patient compliance) of D-GDP every 21 days as follows:
C1: daratumumab 8 mg/kg IV on D2 and on D9
C2-6: daratumumab 16 mg/kg IV on D2 and D9), gemcitabine 1000 mg/sm IV D1 and D8 (gemcitabine on D8 to be skipped in case of grade 3–4 toxicity), cisplatin 75 mg/sm IV D1, dexamethasone 40 mg IV or PO D1-2-3-4-9, G-CSF from D3 to 6, and from D10 to 13 (prolonged if necessary)Maintenance:Starting 28 days after the beginning of C4 or 6 (or in case of toxicity grade > 1, after toxicity is resolved) and up to 24 cycles from start of D-GDP according to the following schedule: daratumumab 16 mg/kg single administration every 2 days
NCT04251065
ATLCAR.CD30 T cells Phase II study of the administration of T lymphocytes expressing the CD30 chimeric antigen receptor (CAR) for R/R CD30+ PTCL II 20 The cellular product consisting of ATLCAR.CD30 cells will be administered via IV injection over 5–10 min through either a peripheral or a central line. The volume of infusion will depend upon the concentration of the cells when frozen and the size of the subject. Administration to eligible subjects will occur within 2–14 days after completing lymphodepleting chemotherapy NCT04083495
AMF13 A phase II open-label multicenter study to assess the efficacy and safety of AFM13 in patients with relapsed or refractory CD30-positive peripheral T cell lymphoma or transformed mycosis fungoides (REDIRECT) II 145 AMF13 is given as weekly IV infusions of 200 mg NCT04101331
AMF13 Bispecific antibody AFM13 combined with NK Cells for patients with recurrent or refractory CD30-positive Hodgkin or non-Hodgkin lymphomas I 30 Patients receive standard of care fludarabine IV over 1 h and standard of care cyclophosphamide IV over 30–60 min on D-4 to -2, AFM13-NK IV over 4 h on D0, and then AFM13 IV over 4 h on D 7, 14, and 21. NCT04074746
AUTO4TRBC1 targeted CAR-T cells A single-arm, open-label, multi-center, phase I/II study evaluating the safety and clinical activity of AUTO4, a CAR T cell treatment targeting TRBC1, in patients with R/R TRBC1-positive selected T cell non-Hodgkin lymphoma I/II 55 Following pre-conditioning with chemotherapy (cyclophosphamide and fludarabine) patients are treated with doses from 25 to 225 × 106 RQR8/aTRBC1 CAR T cells.
Following phase 2 dose determination, patients will be treated with selected doses of RQR8/aTRBC1 CAR T cells (AUTO4).
NCT03590574