Three‑drug targeted treatment for high‑risk CLL with TP53 changes
Optimizing novel agent combination therapy for previously untreated, high risk chronic lymphocytic leukemia
Testing a time‑limited three‑drug combination (acalabrutinib, venetoclax, and obinutuzumab) for people with previously untreated, TP53‑aberrant high‑risk chronic lymphocytic leukemia.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Dana-Farber Cancer Inst NIH-funded |
| Lab location | 1 site (Boston, United States) |
| Project ID | NIH-11128794 on NIH RePORTER |
What this research studies
This phase 2 multicenter trial gives people with newly diagnosed, TP53‑aberrant CLL a time‑limited course of three targeted drugs: acalabrutinib, venetoclax, and the antibody obinutuzumab. How long each person stays on therapy will be guided by sensitive tests for undetectable minimal residual disease (uMRD), with treatment stopped when deep remission is reached. Blood and tumor samples will be collected to study MRD clonal changes, pre‑treatment mitochondrial priming, and genomic complexity using next‑generation sequencing (Adaptive ClonoSEQ). The goal is to link these biological markers to who achieves complete response with uMRD and to monitor safety across participating centers.
Who could benefit from this research
Good fit: Adults with previously untreated chronic lymphocytic leukemia that has a TP53 aberration (deletion or mutation) and who are eligible for targeted therapy would be the ideal candidates.
Not a fit: People with relapsed or refractory CLL, those without TP53 abnormalities, or patients who cannot tolerate these targeted drugs or travel to participating centers are unlikely to benefit from this trial.
Why it matters
Potential benefit: If successful, this approach could produce deeper, time‑limited remissions for people with high‑risk TP53‑aberrant CLL and reduce long‑term treatment exposure.
How similar studies have performed: Prior laboratory and early clinical work showed strong activity for acalabrutinib plus venetoclax and combining those agents with anti‑CD20 antibodies has shown promise, but this specific time‑limited triplet is being tested more directly in a phase 2 setting.
Where this research is happening
Boston, United States
- Dana-Farber Cancer Inst — Boston, United States (Active)
Researchers
- Principal investigator: Davids, Matthew S — Dana-Farber Cancer Inst
- Study coordinator: Davids, Matthew S
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.