Revolutionizing T-cell Acute Lymphoblastic Leukemia (T-ALL) Treatment: A Novel Combination Therapy Offers New Hope

PHASE ONE Foundation has awarded the Leukemia & Lymphoma Society (LLS) and Dr. Wendy Stock of the University of Chicago $250,000 to help fund a Phase 1b/II Study Targeting T-cell Acute Lymphoblastic Leukemia (T-ALL). This grant is in partnership with The Wise Family Foundation.  

T-ALL is an aggressive type of Acute Lymphoblastic Leukemia (ALL) that affects the lymphoid-cell-producing stem cells, particularly a type of white blood cell called T lymphocytes. 

T-ALL represents approximately 15% of pediatric and 25% of adult ALL cases. While survival rates overall have improved during the last decade, 35-40% of patients with T-ALL still relapse, and treatment options are limited beyond first-line therapy. 

“As a relapsed T-ALL patient, I know what it feels like to be told that there are limited treatment options out there for my disease. When the opportunity arose to help fund Dr. Stock’s new trial, PHASE ONE seemed like a great fit as a partner. PHASE ONE funds important, groundbreaking trials, often for underfunded diseases, and this trial fits that bill perfectly. I’m proud to have been involved in helping fundraise for this trial.” –Brennan Wise, The Wise Family Foundation 

To address the critical need for new treatment approaches, Dr. Stock is investigating a novel combination therapy in patients with relapsed T-ALL. 

“Patients with relapse of T-ALL, a disease that affects predominantly adolescents and young adults, have had very limited novel treatment options.  Through early clinical and laboratory translational efforts, our group has developed a very compelling rationale for combination therapy targeting cell death pathways and cell signaling abnormalities in T-ALL.” –Wendy Stock, MD, Anjuli Seth Nayak Professor of Medicine, University of Chicago 

The central dilemma in managing T-ALL lies in the remarkable resilience of leukemia cells. These cells defy programmed cell death by virtue of aberrant signaling mechanisms. Recent research has illuminated the potential of drugs that work by activating the death pathways of leukemia cells, leading to improvements in survival rates for patients with other forms of leukemia. 

In preclinical research published in AACR’s Clinical Cancer Research, Dr. Stock conducted an early-phase clinical trial involving patients who had experienced relapses of ALL. The trial yielded promising results when a class of novel drugs was combined with conventional chemotherapy.  

An example of this new class of drugs includes LP-118, an exciting new drug with dual targeting activity to block proteins critical to the survival of T-ALL cells. 

Additionally, Dr. Stock conducted experiments on mouse models with T-ALL. These preclinical tests demonstrated that LP-118 effectively controlled leukemia progression without causing significant harm to the animals' vital organs. 

During Dr. Stock’s investigations into why some leukemia cells develop resistance to LP-118, she made an intriguing discovery. The resistant cells, in an effort to sustain their growth, activated specific signaling pathways while simultaneously suppressing those responsible for cell death. To address this resistance, Dr. Stock utilized targeted medications, such as Dasatinib, to block these growth-promoting signaling pathways, resulting in a marked increase in the sensitivity of the leukemia cells to LP-118, and, ultimately, cell death. 

Building on these critical preclinical findings, Dr. Stock plans to combine LP-118 with signaling pathway inhibitors like Dasatinib, or related drugs such as Ponatinib, in her Phase 1b/II trial.  

“Through the incredibly generous support of LLS, PHASE ONE, and the Wise Family Foundation, we are thrilled to have received funding to conduct this novel early-phase clinical trial to test a novel targeted BH3 mimetic and ponatinib (a tyrosine kinase inhibitor) for patients with relapsed T-ALL for whom there are otherwise very limited treatment options. We are so grateful to them and their supporters and are focused on trying to improve the lives of our wonderful patients with T-ALL.” –Wendy Stock, MD, Anjuli Seth Nayak Professor of Medicine, University of Chicago 

This approach represents a strategic combination therapy designed to enhance the effectiveness of leukemia treatment in this patient population that is in urgent need of more options. 

“PHASE ONE is proud to partner with LLS and the Wise Family Foundation to fund Dr. Wendy Stock's pioneering T-ALL research. This study marks a pivotal stride in addressing critical deficiencies in treatment options and has the potential to revolutionize T-ALL treatment– delivering newfound hope for patients and their families." –Marc Lebowitz, PHASE ONE Granting Committee Co-Chair