Haematology-Oncology · Clinical trials
Hodgkin Lymphoma Clinical Trials
Approved therapies, the pivotal-trial endpoints they were judged on, the magnitude of benefit — and the drugs that failed their endpoints, and why.
Indication overview
About hodgkin lymphoma — and why its trials are hard
Hodgkin lymphoma is a B-cell-derived lymphoma characterised, in its classical form, by rare malignant Reed-Sternberg cells embedded in an extensive reactive inflammatory infiltrate. It commonly presents with painless lymphadenopathy (often cervical/mediastinal) and sometimes B symptoms, with a bimodal age distribution. It is among the most curable cancers: combination chemotherapy, historically ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine), cures the majority, with radiotherapy used in selected early-stage disease. Response-adapted strategies using interim PET scanning tailor intensity and reduce late toxicity. For advanced or relapsed disease, the CD30-directed antibody-drug conjugate brentuximab vedotin, validated frontline in ECHELON-1 (replacing bleomycin), improved outcomes. Reed-Sternberg cells exploit PD-L1 amplification, making classical Hodgkin lymphoma exquisitely sensitive to PD-1 blockade; nivolumab and pembrolizumab (the latter superior to brentuximab vedotin in relapsed disease in KEYNOTE-204) are now important options, including in combination frontline regimens. Because patients are often young and long-lived, minimising late effects, secondary malignancies, cardiopulmonary toxicity and infertility, is a major goal alongside cure.
Approved therapies & pivotal evidence
What's been approved — and by how much it moved the endpoint
| Drug (brand) | Approved | Setting | Pivotal trial | Primary endpoint | Magnitude of benefit |
|---|---|---|---|---|---|
| Brentuximab vedotin (Adcetris) | 2011 (relapsed); 2018 frontline advanced stage | Relapsed and frontline advanced-stage classical Hodgkin lymphoma | ECHELON-1 (A+AVD vs ABVD) | Modified progression-free survival / overall survival | Superior modified PFS vs ABVD; later analyses showed an overall survival benefit |
| Nivolumab (Opdivo) | 2016 | Relapsed/refractory classical Hodgkin lymphoma (post-transplant/brentuximab); frontline combinations emerging | CheckMate 205 / CheckMate 039 | Overall response rate | High ORR (~65-70%) in heavily pre-treated relapsed disease (PD-1 blockade) |
| Pembrolizumab (Keytruda) | 2017 (relapsed/refractory) | Relapsed/refractory classical Hodgkin lymphoma | KEYNOTE-204 (vs brentuximab vedotin); KEYNOTE-087 | Progression-free survival | KEYNOTE-204 showed superior PFS vs brentuximab vedotin (median ~13.2 vs 8.3 months) |
| ABVD regimen (doxorubicin/bleomycin/vinblastine/dacarbazine) (Combination chemotherapy) | Long-established standard | Frontline early and advanced-stage classical Hodgkin lymphoma | Historical cooperative-group trials (e.g. vs MOPP) | Cure / freedom from progression | High cure rates with less toxicity/infertility than older MOPP; long the backbone of therapy |
| Nivolumab + AVD (Opdivo + chemotherapy) | 2024 (frontline advanced stage) | Frontline advanced-stage classical Hodgkin lymphoma | SWOG S1826 | Progression-free survival | Superior PFS vs brentuximab vedotin + AVD in advanced-stage disease |
Where trials have failed
Drugs that missed their endpoint — and what contributed
The most instructive lessons in hodgkin lymphoma development come from programmes that failed the endpoint that mattered.
| Drug / trial | Endpoint outcome | What contributed |
|---|---|---|
| Bleomycin (within ABVD, as escalated/prolonged use) — RATHL and related response-adapted trials | Dropping bleomycin after a negative interim PET maintained efficacy while reducing pulmonary toxicity, showing prolonged bleomycin added toxicity without clear benefit | Bleomycin-related pulmonary toxicity drove PET-adapted de-escalation and its replacement by brentuximab vedotin in ECHELON-1 |
| Escalated BEACOPP (in some populations) — Comparative frontline trials | Improved disease control but at the cost of higher acute toxicity, infertility and secondary-malignancy risk, limiting its universal adoption | Toxicity/late-effect burden made it unsuitable as a one-size-fits-all standard, especially outside high-risk patients |
Choosing the right endpoint
Primary endpoints that matter in hodgkin lymphoma trials
- Progression-free survival (PFS) — Common primary endpoint; ECHELON-1 used a modified PFS definition
- Overall survival (OS) — Achievable given high curability; demonstrated in mature ECHELON-1 data
- Interim PET (Deauville) response — Guides response-adapted therapy to escalate or de-escalate treatment
- Overall response rate (ORR) — Key for relapsed/refractory checkpoint-inhibitor trials
- Freedom from treatment failure / late toxicity — Especially important given young patients and long survivorship
How iNGENū runs hodgkin lymphoma trials
Physician-led design, built for FDA submission
Endpoint & biomarker strategy
Board-certified specialists design endpoints and patient selection aligned to current FDA guidance for this indication.
FDA-ready data
Built to ICH-GCP and 21 CFR 312.120, with direct FDA submission — data accepted by the FDA, EMA and MHRA.
Faster, lower-cost delivery
~4-week ethics via the TGA CTN scheme, up to 43.5% R&D rebate, and 80–90% below US CRO cost.
Request a fixed-milestone proposal and a tailored endpoint & feasibility summary for this indication.
Frequently asked questions
Hodgkin Lymphoma clinical trials — FAQs
Is Hodgkin lymphoma curable?
Why is Hodgkin lymphoma so responsive to PD-1 inhibitors?
Why focus on reducing treatment toxicity?
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