Table 2.
Selected open or recently completed phase III and phase II clinical trials in Hodgkin lymphoma*
| Title Frontline | Regimen | Population | NCT number/sponsor | Estimated enrollment | Start date/completion date | Preliminary data |
|---|---|---|---|---|---|---|
| ECHELON 1 | ABVD vs AAVD | Advanced stage (IIb–IV) | 01712490 Millennium Pharmaceuticals, Inc. | 1240 | November 2012–December 2015 | Phase 1 AAVD: 3-y FFS = 96%, OS = 100% |
| HD16 | ABVD × 2 +/- 20 Gy IFRT | Early stage without bulk (Ia–IIb) | NCT00736320 University of Cologne | 1150 | November 2009–May 2020 | |
| HD18 | escBEACOPP x 2 + PET+ → escBEACOPP x 6 vs escBEACOPP x 6 + rituximab PET- → esc BEACOPP × 4 vs escBEACOPP × 8 | Advanced stage HL (IIB with bulky disease, III, IV) | 00515554 University of Cologne | 1500 | May 2008–July 2014 | PET+ 3-y interim analysis: PFS = 91.4% for BEACOPP; 93% for R-BEACOPP; OS = 96.5% vs 94.4% at 3 y |
| BV and combination chemotherapy | ABVEPC vs ABvVEPC + response-directed ISRT | High-risk/ advanced-stage pediatric classical HL (2–18 y) | 0216643 COG | 600 | March 2015–November 2019 | |
| CALGB: response-based therapy assessed by PET scan | ABVD +/- BEACOPP + radiation | Bulky stage I and stage II cHL | 01118026 CALGB | 123 | September 2010–July 2017 | |
| BV + AVD | BV × 2 → AVD + BV x 4–6 | Limited-stage HL | 01534078 Mass General Hospital | 34 | March 2012–April 2015 | CR = 88%, PFS = 90%, OS = 97% at 14 mo; grade 3–4 neuropathy = 24% |
| Sequential BV → AVD | BV-AVD | Elderly HL | NCT01476410 Northwestern | 48 | November 2011–May 2016 | |
| Sequential BV → AVD | BV + AVD and 30 Gy IFRT | Early-stage unfavorable HL | 01868451 Memorial Sloan Kettering Cancer Center | 30 | May 2013–May 2016 | |
| BV + DTIC or bendamustine | BV + dacarbazine or bendamustine | Elderly (60 y and older) | NCT01716806 Seattle Genetics | 70 | October 2012–October 2018 | Interim analysis 100% ORR for both combinations |
| Response-adjusted therapy for Hodgkin lymphoma (RATHL) | 2 cycles ABVD →PET- ABVD vs AVD × 4 PET + BEACOPP x 6 vs escBEACOPP × 4 +/- IFRT | Advanced stage (IIB with bulky disease, III, IV) | CRUK/07/033 | 1214 | Median FU of 36.3 mo, PFS = 85.4% ABVD vs 84.4% AVD; OS = 97% ABVD vs 97.5% AVD | |
| AEPA | (BV, etoposide, prednisone, doxorubicin) × 2, CAPDac (cyclophosphamide, BV prednisone, dacarbazine) × 4, with low-dose IFRT | Advanced-stage pediatric | 01920932 Pediatric HL Consortium (St. Jude, DFCI, Stanford) | 77 | August 2013–August 2021 | |
| Targeted BEACOPP variants | BrECADD, BrECAPP | Newly diagnosed advanced stage | German Hodgkin Lymphoma Study Group | 104 | October 2012–May 2014 | BrECADD: CRR = 88%, CR/CRu = 88%, and 18 month PFS = 89%; BreCAP: CRR = 86%, CR/CRu = 94%, and 18 month PFS = 93% |
| Relapsed | ||||||
| BV first salvage | BV | HL in first relapse | 01393717 City of Hope Medical Center | 57 | October 2011–December 2015 | ORR (CR + PR) = 69%, CR = 33% |
| E4412 | BV + ipilimumab and nivolumab | Relapsed HL (first or later) | NCT01896999/ECOG 4412 | 70 | Jan 2014–December 2017 | Preliminary efficacy BV + ipilimumab: ORR = 72%, CR = 50% |
| BV bendamustine | BV + bendamustine | Relapsed HL pre-ASCT | 01874054 Seattle Genetics, Inc. 01657331 Columbia University | 55 71 | July 2012 June 2013– May 2015 October 2015 | CR = 82%, ORR = 94% ; stem cell mobilization and collection was adequate |
| BV + gemcitabine | Pediatric and AYA HL in first relapse | 01780662 COG | 63 | Phase 1: January 2013; phase 2: February 2015–2018 | ||
| CheckMate | Nivolumab | Relapsed HL | 0218738 Bristol-Myers Squibb | 120 | July 2014–May 2016 | Interim report on 80 patients: ORR = 66%, (57.5% PR, 8.8% CR); six-mo PFS = 77% (63) |
| Nivolumab | Pediatric relapsed HL | 02304458 COG | 204 (multiple tumor types); 20 with HL | February 2015–November 2016 | ||
| Pembrolizumab | Relapsed HL post-ASCT | 02362997 Dana-Farber Cancer Institute | 60 | March 2015–March 2022 | Phase 1: ORR of 53% in 15 patients, (CR = 20%, PR = 33%) | |
| Keynote | Pembrolizumab | R/R HL | NCT02453594 Merck | 180 | June 2015–May 2017 | 60 patients (cohorts 1 and 2); cohort 1: ORR = 70%, CR = 20%, PR = 50%; cohort 2: ORR = 80% CR = 27%, PR = 53% (64) |
| BV and nivolumab | BV + nivolumab | Frontline elderly HL | NCT02758717 | 75 | May 2016–February 2018 | |
| BV and nivolumab | BV + nivolumab × 4 cycles | First relapse HL | NCT02572167 | 60 | October 2015–May 2020 |
*
AAVD = brentuximab, adriamcyin vinblastine, dacarbazine; ABVD = doxorubicin, bleomycin, vinblastine, dacarbazine; AEPA = brentuximab, etoposide, prednisone, adriamycin; ASCT = autologous stem cell transplant; BEACOPP = bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procabazine, prednisone; BrECADD = brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone; BreCAP = brentuximab, cyclophosphamide, adriamycin, prednisone; BV = brentuximab vedotin; CALGB = Cancer and Leukemia Group B; CR = complete response; HL = Hodgkin lymphoma; IFRT = involved field radiotherapy; ISRT = involved site radiotherapy; NCT = National Center for Tumor Diseases; ORR = overall response rate; OS = overall survival; PET = positron emission tomography; PFS = progression-free survival; PR = partial response; R/R = relapsed or refractory.