Three‑drug targeted treatment for high‑risk CLL with TP53 changes
Official title: Optimizing novel agent combination therapy for previously untreated, high risk chronic lymphocytic leukemia
Funded at Dana-Farber Cancer Inst · NIH-11128794 · Data updated 2026-11-12
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 start | September 15, 2022 |
| Project end | June 30, 2027 |
| Funding year | 2025 |
| Award (this year) | $403,340 |
| NIH project number | 5R01CA266298-04 |
| Project ID | NIH-11128794 on NIH RePORTER |
Who could benefit from this research
✓Could help
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.
✕Less likely to help
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.
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.
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 gone: 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
-
Dana-Farber Cancer Inst
Boston, United States Active
Researchers
- Principal investigator: Davids, Matthew S — Dana-Farber Cancer Inst
- Study coordinator: Davids, Matthew S
Related research
Other NIH-funded projects on the same topics.
-
Tracing how chronic lymphocytic leukemia can change into Richter’s syndrome
A physician-scientist is studying why CLL sometimes changes into Richter’s syndrome and how this transition happens at the genetic level, with the goal of better outcomes for people living with CLL.
-
Paradigm shift in managing untreated chronic lymphocytic leukemia in older adults
A Mayo Clinic doctor is leading a national collaboration to advance new frontline treatments for older adults with chronic lymphocytic leukemia.
-
AVO: a new triplet therapy for untreated high-risk CLL
A new, time-limited combination therapy (acalabrutinib, venetoclax, and obinutuzumab) is being tested for people with newly diagnosed high-risk CLL to see how well it works and how safe it is.
-
Rewiring cancer pathways to trigger death in chronic lymphocytic leukemia
A Stanford-led study aims to use a new class of small molecules to flip cancer-driving signals so CLL cells die, offering hope for patients who have exhausted other therapies.
-
METTL3's role in driving a stubborn form of chronic lymphocytic leukemia
A cancer-related study looks at how METTL3 helps a common leukemia (CLL) grow and resist treatment, with the goal of finding better therapies.
-
Understanding why BTK inhibitors stop working in chronic lymphocytic leukemia
Researchers are studying why some people with chronic lymphocytic leukemia stop benefiting from BTK inhibitors and how to overcome that resistance.
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.