In short
While chemotherapy (e.g., R-CHOP) remains a standard first-line treatment for non-Hodgkin lymphoma, among high-risk and relapsed patients who do not respond adequately
Treatment considerations include disease heterogeneity, patient age and comorbidities, access to diagnostic and advanced therapeutic options, and the challenges related to intensive treatments, costs, and the availability of novel therapies – factors that increase complexity and risk for sponsors
Amidst a rapidly evolving SoC landscape, the sponsor of a non-Hodgkin lymphoma trial engaged PSI to execute an aggressive recruitment strategy to win the race to market
PSI’s strategy drove the trial to surpass initial projections by being consistently on or ahead of schedule and finishing enrollment in under two years, demonstrating that timely, predictable enrollment is possible even in dynamic conditions
Non-Hodgkin lymphomas: Challenges and perspectives
Non-Hodgkin lymphomas are a diverse group of blood cancers. Among more than 60 different types (characterized by cell type and speed of growth), examples include:
- Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma, with an incidence of approximately 7 people per 100,000 globally [1, 2], and is associated with rapid and painful lymph node swelling, fever, weight loss, and potential organ failure [3]
- Chronic lymphocytic leukemia (CLL) is also relatively common, with an incidence of just under 5 people per 100,000 [4] and impacts patients by weakening their immune system leading to chronic fatigue, among other symptoms [5]
- Burkitt lymphoma is an aggressive and fast-growing B-cell lymphoma requiring immediate and intensive chemotherapy to combat high tumor burden [6]
- Peripheral T-cell lymphoma (PTCL) is a rare and aggressive blood cancer of T-cell origin, characterized by fast-growing tumors presenting as swollen lymph nodes [7] and often highly drug-resistant and accompanied by unsatisfactory treatment outcomes [8]
- AIDS-related lymphoma, the most common lymphoma in patients positive for HIV [9]; the clinical course is often much more aggressive than in patients without HIV, and accounts for up to 30% of all AIDS-related causes of death [9]
While chemoimmunotherapy regimens (R-CHOP) succeed for many patients with non-Hodgkin lymphoma, high-risk or relapsed disease remains a focus of intensive research [10]. Efforts to enhance the effectiveness of R-CHOP regimens in patients who do not respond have, thus far, shown limited success [11, 12]. Whilst differential responses to first-line R-CHOP combination are expected, improved regimens are needed.
In the face of changing SoC, oncology trials must take a proactive, forward-looking approach to feasibility: Will a trial enroll as projected, and if successful, will the new therapy quickly deliver value in a competitive market?
The challenge
This case study describes a sponsor’s trial in one of the most frequently diagnosed subtypes of non-Hodgkin lymphoma. Clinical development in this indication is particularly sensitive to timing, as new therapeutic options and shifting standards of care can quickly impact trial feasibility and relevance. The sponsor launched their trial evaluating a novel therapy in combination with an established treatment backbone. Key challenges included:
- Conducting a large global trial in a competitive and rapidly-evolving treatment landscape
- Delivering aggressive enrollment timelines, before new therapies became widely available
- Managing complexity across multiple countries, sites, and regulatory environments
- Ensuring consistency and reliability
Against these challenges (and in particular, rapid therapeutic advances), the sponsor needed PSI to be ready to tackle an aggressive recruitment plan and complete enrollment in under 2 years, while providing a stable, reliable partnership for success.
The solution
On-time startup
A structured, data-driven approach to site identification and selection was critical – a broad pool of sites were assessed globally, and high-performing sites prioritized, based on feasibility and enrollment potential. A large number of sites across multiple regions were activated ahead of schedule; this close collaboration allowed flexible approaches to feasibility and initiation, including using remote processes where needed.
PSI worked closely with sites to assess the COVID 19 pandemic’s impact on activation readiness and offered various solutions for remote visits.
We knew which sites were open to recruitment and onsite visits, which were allowing remote monitoring visits, and which were completely shut down. With a planned first site activation date [...] for this study, we worked closely with sites to understand how the pandemic affected their ability to meet the planned dates. We also offered them several technical options that allowed us to conduct site selection visits remotely.
Operational consistency
Maintaining continuity in key project roles ensured stability throughout the trial, even as external conditions changed. Local teams closely tracked regulatory progress to minimize delays between submissions and approvals, keeping timelines compressed and predictable.
On behalf of the entire [Sponsor] team, this is to express our sincere appreciation for all of your hard work in the past weeks and months to set up the trial and to engage investigators. You have already removed a lot of our stress by getting many investigators on board and we fully acknowledge that this would not happen without your continuous effort and support.
Sustained momentum
To meet ambitious timelines, all stakeholders aligned around a single objective: Rapid and consistent patient enrollment. Maintaining the momentum of the study was crucial. This is particularly true in oncology, where longer trial lengths (and startup times) make the trials susceptible to changing standards of care, and newly available therapies.
Tactics included:
- Continuous engagement with sites and investigators
- Tailored patient outreach approaches adapted to local contexts
- Performance tracking and motivation/competition across regions and country teams
- Strong coordination across data, monitoring, and operational teams
I would like to thank you for your efforts and stellar engagement so far. It is great to see that by yesterday evening patient 100 was randomized in the US. Please convey our appreciation to your teams and take a moment to celebrate this milestone.
The outcome
Full enrollment (approximately several hundred patients) was achieved within the two year timeframe as projected. Even in complex, competitive indications, disciplined planning and execution can enable predictable delivery.
The study met its primary endpoint, and the sponsor could move to regulatory filing on time, as expected.
The trial’s success is a direct reflection of the effort of more than 500 people from the sponsor, PSI, and our vendors working closely together. Besides on-time patient enrollment, patient retention is so important for the final deliverable: Clean data. This has been reached through intense collaboration of the team. Merging multiple data sources from external vendors on an ongoing basis required experience, resilience and continuous follow up from the site and the study teams. We were able to keep the sites motivated to answer queries up to the primary database lock.
Key takeaways
Predictable enrollment in complex global trials is not accidental, it requires early strategic planning, the right network, and continuous operational alignment. The most important differentiator is not a single tactic, but the ability to synchronize the moving parts – patients, investigators, site support staff, data monitors, CRAs, sponsor colleagues, and many more – into a system that consistently delivers on time, protecting study milestones, and .
Each patient is more than a datapoint, and your CRO is so much more than the sum of its parts.
Contact PSI for your hematology-oncology needs
Abbreviations
AIDS, acquired immunodeficiency syndrome;
CLL, chronic lymphocytic leukemia;
COVID-19, Coronavirus-19;
CRA, Clinical Research Associate;
CRO, Contract Research Organization;
DLBCL, diffuse large B-cell lymphoma;
HIV, human immunodeficiency virus;
PTCL, peripheral T-cell lymphoma;
R-CHOP, combination chemo/immunotherapy regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone).
References
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2. van Leeuwen, M.T., et al., Lymphoid neoplasm incidence by WHO subtype in Australia 1982-2006. Int J Cancer, 2014. 135(9): p. 2146–56.
3. Wang, S., et al., The impact of clinical manifestations on the prognosis of diffuse large B-cell lymphoma. Ther Adv Hematol, 2026. 17: p. 20406207251410405.
4. Hallek, M., Chronic Lymphocytic Leukemia: 2025 Update on the Epidemiology, Pathogenesis, Diagnosis, and Therapy. Am J Hematol, 2025. 100(3): p. 450–480.
5. Molica, S. and Allsup, D., Chronic Lymphocytic Leukemia Care and Beyond: Navigating the Needs of Long-Term Survivors. Cancers (Basel), 2025. 17(1).
6. Ribrag, V., et al., Diagnosis and treatment of Burkitt lymphoma in adults: clinical practice guidelines from ERN-EuroBloodNet. Lancet Haematol, 2025. 12(2): p. e138–e150.
7. Ondrejka, S.L. and de Leval, L., Modern Approach to Nodal T-Cell Lymphomas. Adv Anat Pathol, 2025. 32(3): p. 220–238.
8. Luan, Y., et al., Therapeutic challenges in peripheral T-cell lymphoma. Mol Cancer, 2024. 23(1): p. 2.
9. Berhan, A., Bayleyegn, B., and Getaneh, Z., HIV/AIDS Associated Lymphoma: Review. Blood Lymphat Cancer, 2022. 12: p. 31–45.
10. Shi, Y., et al., Advances in biology, diagnosis and treatment of DLBCL. Ann Hematol, 2024. 103(9): p. 3315–3334.
11. Abrisqueta, P., New Insights into First-Line Therapy in Diffuse Large B-Cell Lymphoma: Are We Improving Outcomes? J Clin Med, 2024. 13(7).
12. Langerbeins, P., et al., Poor efficacy and tolerability of R-CHOP in relapsed/refractory chronic lymphocytic leukemia and Richter transformation. Am J Hematol, 2014. 89(12): p. E239–43.
