Acute myeloid leukemia (AML) moves quickly, attacking the bone marrow. Over 124,000 people are diagnosed with AML each year worldwide. Most patients receive chemotherapy, and the treatments often lead to remission, but the five-year survival rate remains less than 30 percent. Researchers around the world are working to change that.
In a previous article, we discussed what the current AML research landscape looks like, exploring where those trials are taking place and the patient segments they target. As of February 9, 2024, there were nearly 1500 active AML trials and more start every month. At Precision for Medicine, we frequently participate in these efforts. In this article, we will outline a recent project we supported, discussing our approach as well as lessons learned.
Case Study Demographics
| Number of Sites | 17 sites in EU; 14 in US |
| Countries | US, UK, France, Italy, Germany, Spain |
| Trial Design | Phase 1B Dose Escalation: ~100 Patients; Phase 2 Expansion: 100+ Patients |
| Services | Full service minus medical monitoring and pharmacovigilance |
Acknowledging Precision’s expertise in AML, a sponsor trusted us to spearhead a comprehensive study that spanned the US and five European nations. This collaboration not only highlighted our technical abilities, but also showcased the strength of our relationship with sponsors in driving meaningful outcomes. For this case study, we will examine an ongoing Phase 1-2 trial treating AML patients and discuss our approach as well as lessons learned.
Our Strategy for Success
Precision’s strategy was multi-faceted. Beyond just managing the trial, we introduced best practices, and tapped into our experience to guide the current project. From capitalizing on our accumulated AML knowledge to maintaining open lines of communication with key client stakeholders, we ensured aligned goals and a deeply collaborative environment. Precision’s extensive experience with AML studies set a foundation for effective management of the current trial.
Engaged Investigators & Streamlined Enrollment
This study included cohorts for relapsed patients, untreated patients, refractory patients, and there were zero issues with enrollment in both dose escalation and expansion. Patients were lining up to the point that we had a waitlist for participation. We hit all targets well before deadlines. There were two reasons for this:
- Supportive investigators: There was a buzz around this trial. Many of the people involved were very enthusiastic about the molecule we were testing. It had already passed proof-of-concept. While that won’t happen every time, regular calls with investigators every two weeks and our support drove that enthusiasm, streamlining recruitment. We shared what was happening at different sites and that continual exposure helped keep the trial top of mind.
- Inclusion criteria that followed standard of care: Once we found sites that used this practice, we were able to screen patients before they became candidates very effectively and minimized protocol amendments. We also worked with the sites to prepare for the influx of trial participants.
Focused Collaboration & Adaption
The high level of interest in the trial prompted the Sponsor to include additional cohorts. As the scope of the patient population expanded, we were able to support and drive those efforts. Precision used a high level of planning, coordination, and communication to make that happen as smoothly as it did. Our teams’ comprehensive cohort management plans helped make this happen in a seamless way. Sites were able to reach out about specific patients and get a response within 24–48 hours as to whether the patient could be enrolled.
We also moved from site allocations (the initial strategy) to competitive enrollment (our strategy adaptation) which helped us reach target enrollment quickly. Some sites struggled with recruitment while others had wait lists to join the trial. Being flexible and adaptable helped leverage that interest in the trial.
Robust & Layered Communication Framework
With so much interest in the trial and the addition of these extra cohorts, communication was key to success. What made it unique was that we used a layered management oversight approach instead of a stepped approach. Meetings were staggered so that every week a different combination of team members met to discuss study progress. This approach meant that issues could be unearthed and escalated readily, and potential risks could be mitigated. Continuous monitoring played a role as well. Our Clinical Science Analytics & Insights (CSAI) team provided a holistic review of the data for clinical sense and protocol compliance. In this trial, the CSAI team’s continuous scientific review led to regular patient data cleaning and facilitated achieving quicker database cuts, freezes and the final lock.
Understanding the Role & Benefits of Precision’s CSAI
| Consistent Support | CSAI Manager & Scientist resource assignment consistent across the Sponsor’s projects allowing the CSAI team to apply consistency to data review rules, conventions, guidelines, and support the internal and external team as appropriate. |
| In-depth Knowledge | Holistic manual clinical sense review of complex data applied by the CSAI Scientists (e.g., AML Disease Assessment Criteria, CTCAE grading, AESIs, DLTs) mitigates risk through early identification of complex data issues and inconsistencies. |
| Data Cleaning Process | CSAI supports the data cleaning process, assisting with identifying patients ready for final data cleaning, supporting the DMs and CTMs with the Clean Patient Report review, along with attending weekly data cleaning meetings. |
| Identify Issues and Retrain | Through Centralized Clinical Sense Data Review, there is a gained proficiency supporting real-time quality data driven decisions and outcomes. Trends and issues identified throughout the study are highlighted with guidance provided to the team for resolution. |
The CSAI Scientist originates many insights that are then shared with the Sponsor, focusing on safety, efficacy and endpoint data. Weekly reporting and frequent lab monitoring is supported by the CSAI visualization tools:
SMART Patient Profiles (SPP)
- Individually considers patient data to discover anomalies unique to that patient.
- Enables individual holistic data review.
All Patient Data Workbook (APDW)
- All patient study data flagged for outliers.
- Supports aggregate review, data filtering, pivot tables, outliers, etc.
Lessons Learned
This AML trial highlighted several lessons that will be invaluable for future AML trials.
Frequent Meetings Improve Engagement
- Meeting frequency improves engagement from sites and investigators and kept the project aligned to Sponsor’s goals during the expansion stage.
- Biweekly safety calls were crucial not only for ensuring the trial’s safety but also for fostering engagement from sites and facilitating constructive scientific discourse.
Deep Engagement Pays Off
- Building a partnership-style relationship, rather than a transactional one, can lead to more comprehensive collaboration and success, as evidenced by the expanding partnership between Precision and the sponsor.
- Higher enrollment and the addition of new cohorts required additional touchpoints.
Flexibility & Agility Can Make Better Trials
- We moved from site allocation to competitive enrollment because some sites were attracting more participants. Introducing this flexibility helped us reach milestones faster and more efficiently.
- However, our high-enrolling sites also required additional oversight and on-site monitoring to handle their increased enrollment volume; staying on top of data cleaning was the key to success.
Takeaway
This case study exemplifies the outcomes achievable through combined expertise and commitment. The Phase 1-2 AML study was successfully executed, leading to a growing partnership and the initiation of further studies and collaboration.
- Clinical Trial Achievements: The AML Phase 1-2 study, with sites across the US and Europe, successfully completed Phase 1 and concluded Phase 2 enrollment.
- Strengthened Collaborations: The initial trial set the foundation for a strong partnership with this biotech sponsor, now encompassing three ongoing trials across various cancer types. An additional trial is currently in development, underscoring the sustained robustness of the partnership.
Our combined effort in this study underscores the importance of expertise and commitment. With successful completion of the AML Phase 1-2 study and ongoing collaborations, this partnership solidifies the promise of our joint pursuits in advancing AML research and potential treatments.
Choosing Precision for Your Next AML Trial
Precision is your trusted partner in AML drug development, combining staff expertise with technology to propel your program forward. Our research encompasses a broad spectrum of therapeutic classes and drug targets, and we stand at the forefront of pioneering AML approaches. With Precision, you’re always one step ahead.
