Combination regimens including new agents for the first-line treatment of PTCL patients
| Combination . | Phase . | Study status . | Study description . | Available results . | Reference or NCT no. . |
|---|---|---|---|---|---|
| Pralatrexate + CEOP | 2 | Completed | Alternation of CEOP and pralatrexate in untreated patients with PTCL. AutoSCT permitted in transplant-eligible patients. Pralatrexate given at 30 mg/m2 on days 15, 22, 29. Cycle duration: 6 wk. 6 planned cycles. | 33 patients enrolled; 64% PTCL-NOS. 45% of patients received autoSCT. ORR, 70%; CR, 52%; 2-y PFS, 39%; 2-y OS, 60%. PFS and OS not significantly improved if compared with reported data of CHOP and CHOEP. | 81 |
| Pralatrexate + CHOP | 1 | Ongoing | To find the MTD of pralatrexate in combination with CHOP in untreated PTCL. Up to 5 sequential escalating dose cohorts of pralatrexate (MAD, 30 mg/m2), given on days 1 and 8, together with CHOP. One expansion cohort with MTD of pralatrexate. | Final data collection for primary outcome measures: April 2017. | NCT02594267 |
| Romidepsin + CHOP | 1/2 | Completed | To find the MTD of romidepsin in combination with CHOP in untreated PTCL. Three treatment cohorts of romidepsin (8, 10, 12 mg/m2) starting from 10 mg/m2. One expansion cohort with MTD of romidepsin. | 37 patients enrolled. Romidepsin MTD was 12 mg/m2, given at days 1 and 8 every 3 wk. ORR, 68%; CR, 51%; 18-mo PFS, 77%. Adverse events: hematological. Cardiovascular events observed, but questionable relationship with romidepsin. | 82 |
| 3 | Ongoing | Randomized study to compare efficacy of romidepsin + CHOP vs CHOP in untreated PTCL. Romidepsin given at 12 mg/m2 on days 1 and 8 every 3 wk. 6 planned cycles. | Final data collection for primary outcome measures: July 2019. | NCT01796002 | |
| Romidepsin + CHOEP | 1/2 | Ongoing | To find the MTD of romidepsin in combination with CHOEP before autoSCT in young (<65 y) untreated patients with PTCL. Four treatment cohorts of romidepsin (8, 10, 12, 14 mg/m2) starting from 12 mg/m2. One expansion cohort with MTD of romidepsin. | Final data collection for primary outcome measures: September 2017. | NCT02223208 |
| Belinostat + CHOP | 1 | Completed | To find the MTD of belinostat in combination with CHOP in untreated PTCL. Five treatment cohorts of belinostat, 1000 mg/m2 for 1-5 d, together with CHOP, starting from cohort 3 (1000 mg/m2, days 1-3). One expansion cohort with MTD of belinostat. | 23 patients enrolled. Belinostat MTD was 1000 mg/m2, days 1-5 (cohort 5). ORR (18 evaluable patients), 89%; CR, 72%. Adverse events: those typically seen with CHOP chemotherapy. | 83 |
| Brentuximab + CHP | 3 | Ongoing | Double-blind, randomized, placebo-controlled study to compare efficacy of brentuximab vedotin + CHP (without vincristine to avoid excessive neurotoxicity) vs CHOP in CD30+ mature T-cell lymphoma (ECHELON-2 trial). | Final data collection for primary outcome measures: December 2017. | NCT01777152 |
| Alemtuzumab + CHOP | 2 | Completed | Alemtuzumab given at 30 mg/cycle for the first 4 (part 1) or 8 (part 2) cycles every 4 wk in combination with CHOP in untreated patients with PTCL. | 24 patients enrolled; 58% PTCL-NOS. ORR, 75%; CR, 71% (50% for PTCL-NOS); 2-y FFS, 48%; 2-y OS, 53%. Relevant adverse events: infectious complications; CMV reactivation (9%). | 86 |
| 2 | Completed | Alemtuzumab given at 90 mg/cycle for 8 cycles every 2 wk in combination with CHOP in untreated patients with PTCL. | 20 patients enrolled; 50% PTCL-NOS. ORR, 90% (80% for PTCL-NOS); CR, 65%; 2-y EFS, 30% (10% for PTCL-NOS); 2-y OS, 55% (30% for PTCL-NOS). | 87 | |
| 3 | Ongoing | Randomized study to compare efficacy of alemtuzumab + CHOP vs CHOP, followed by autoSCT, in young (<60 y) untreated PTCL patients. Alemtuzumab given at total dose of 360 mg (then of 120 mg after amendment for toxicity). CHOP given every 14 d for 6 planned cycles (ACT-1 trial). | Data presented for the first 68 patients. PTCL-NOS: 56% (A-CHOP) vs 55% (CHOP). Non–arm-specific 1-y PFS, 54%; 1-y OS, 78%. Estimated study completion date: December 2016. | 88, NCT00646854 | |
| 3 | Completed | Randomized study to compare efficacy of alemtuzumab (A) + CHOP vs CHOP in elderly (>60 y) untreated PTCL patients. Alemtuzumab given at the total dose of 360 mg (then of 120 mg after amendment for toxicity). CHOP given every 14 d for 6 planned cycles (ACT-2 trial). | 116 patients enrolled; 39% PTCL-NOS. CR 60% (A-CHOP) vs 43% (CHOP); 3-y PFS 26% (A-CHOP) vs 29% (CHOP); 3-y OS 38% (A-CHOP) vs 56% (CHOP). Differences in PFS and OS do not reach statistical significance. Survival not improved mostly because of treatment toxicity. | 89 |
| Combination . | Phase . | Study status . | Study description . | Available results . | Reference or NCT no. . |
|---|---|---|---|---|---|
| Pralatrexate + CEOP | 2 | Completed | Alternation of CEOP and pralatrexate in untreated patients with PTCL. AutoSCT permitted in transplant-eligible patients. Pralatrexate given at 30 mg/m2 on days 15, 22, 29. Cycle duration: 6 wk. 6 planned cycles. | 33 patients enrolled; 64% PTCL-NOS. 45% of patients received autoSCT. ORR, 70%; CR, 52%; 2-y PFS, 39%; 2-y OS, 60%. PFS and OS not significantly improved if compared with reported data of CHOP and CHOEP. | 81 |
| Pralatrexate + CHOP | 1 | Ongoing | To find the MTD of pralatrexate in combination with CHOP in untreated PTCL. Up to 5 sequential escalating dose cohorts of pralatrexate (MAD, 30 mg/m2), given on days 1 and 8, together with CHOP. One expansion cohort with MTD of pralatrexate. | Final data collection for primary outcome measures: April 2017. | NCT02594267 |
| Romidepsin + CHOP | 1/2 | Completed | To find the MTD of romidepsin in combination with CHOP in untreated PTCL. Three treatment cohorts of romidepsin (8, 10, 12 mg/m2) starting from 10 mg/m2. One expansion cohort with MTD of romidepsin. | 37 patients enrolled. Romidepsin MTD was 12 mg/m2, given at days 1 and 8 every 3 wk. ORR, 68%; CR, 51%; 18-mo PFS, 77%. Adverse events: hematological. Cardiovascular events observed, but questionable relationship with romidepsin. | 82 |
| 3 | Ongoing | Randomized study to compare efficacy of romidepsin + CHOP vs CHOP in untreated PTCL. Romidepsin given at 12 mg/m2 on days 1 and 8 every 3 wk. 6 planned cycles. | Final data collection for primary outcome measures: July 2019. | NCT01796002 | |
| Romidepsin + CHOEP | 1/2 | Ongoing | To find the MTD of romidepsin in combination with CHOEP before autoSCT in young (<65 y) untreated patients with PTCL. Four treatment cohorts of romidepsin (8, 10, 12, 14 mg/m2) starting from 12 mg/m2. One expansion cohort with MTD of romidepsin. | Final data collection for primary outcome measures: September 2017. | NCT02223208 |
| Belinostat + CHOP | 1 | Completed | To find the MTD of belinostat in combination with CHOP in untreated PTCL. Five treatment cohorts of belinostat, 1000 mg/m2 for 1-5 d, together with CHOP, starting from cohort 3 (1000 mg/m2, days 1-3). One expansion cohort with MTD of belinostat. | 23 patients enrolled. Belinostat MTD was 1000 mg/m2, days 1-5 (cohort 5). ORR (18 evaluable patients), 89%; CR, 72%. Adverse events: those typically seen with CHOP chemotherapy. | 83 |
| Brentuximab + CHP | 3 | Ongoing | Double-blind, randomized, placebo-controlled study to compare efficacy of brentuximab vedotin + CHP (without vincristine to avoid excessive neurotoxicity) vs CHOP in CD30+ mature T-cell lymphoma (ECHELON-2 trial). | Final data collection for primary outcome measures: December 2017. | NCT01777152 |
| Alemtuzumab + CHOP | 2 | Completed | Alemtuzumab given at 30 mg/cycle for the first 4 (part 1) or 8 (part 2) cycles every 4 wk in combination with CHOP in untreated patients with PTCL. | 24 patients enrolled; 58% PTCL-NOS. ORR, 75%; CR, 71% (50% for PTCL-NOS); 2-y FFS, 48%; 2-y OS, 53%. Relevant adverse events: infectious complications; CMV reactivation (9%). | 86 |
| 2 | Completed | Alemtuzumab given at 90 mg/cycle for 8 cycles every 2 wk in combination with CHOP in untreated patients with PTCL. | 20 patients enrolled; 50% PTCL-NOS. ORR, 90% (80% for PTCL-NOS); CR, 65%; 2-y EFS, 30% (10% for PTCL-NOS); 2-y OS, 55% (30% for PTCL-NOS). | 87 | |
| 3 | Ongoing | Randomized study to compare efficacy of alemtuzumab + CHOP vs CHOP, followed by autoSCT, in young (<60 y) untreated PTCL patients. Alemtuzumab given at total dose of 360 mg (then of 120 mg after amendment for toxicity). CHOP given every 14 d for 6 planned cycles (ACT-1 trial). | Data presented for the first 68 patients. PTCL-NOS: 56% (A-CHOP) vs 55% (CHOP). Non–arm-specific 1-y PFS, 54%; 1-y OS, 78%. Estimated study completion date: December 2016. | 88, NCT00646854 | |
| 3 | Completed | Randomized study to compare efficacy of alemtuzumab (A) + CHOP vs CHOP in elderly (>60 y) untreated PTCL patients. Alemtuzumab given at the total dose of 360 mg (then of 120 mg after amendment for toxicity). CHOP given every 14 d for 6 planned cycles (ACT-2 trial). | 116 patients enrolled; 39% PTCL-NOS. CR 60% (A-CHOP) vs 43% (CHOP); 3-y PFS 26% (A-CHOP) vs 29% (CHOP); 3-y OS 38% (A-CHOP) vs 56% (CHOP). Differences in PFS and OS do not reach statistical significance. Survival not improved mostly because of treatment toxicity. | 89 |
Source: https://clinicaltrials.gov, accessed July 2016.
ACT, Alemtuzumab and CHOP in T-cell Lymphoma; CEOP, cyclophosphamide, etoposide, vincristine, and prednisone; CMV, cytomegalovirus; ECHELON-2, A Comparison of Brentuximab Vedotin and CHP With Standard-of-care CHOP in the Treatment of Patients With CD30-positive Mature T-cell Lymphomas; MAD, maximum administered dose; MTD, maximum tolerated dose.