Clinical Trials | Phase 1 Study of Combination Tovorafenib (DAY101) and Rituximab Treatment in Relapsed or Refractory Classical Hairy Cell Leukemia and Phase 2 Randomized Study Comparing Tovorafenib (DAY101) and Rituximab with Cladribine and Rituximab for Front-line Treatment of Classical Hairy Cell Leukemia

The University of Virginia is conducting a clinical research study for adults ages 18 and over for patients with classical hairy cell leukemia who have not received prior treatment for their disease. The purpose of this study is to test the safety and effectiveness of a drug called Tovorafenib (DAY101). Tovorafenib has been approved by the FDA to treat other cancers but has not yet been approved to treat hairy cell leukemia. This study is divided into two parts: Part 1: The purpose of this part of the study is to look at the safety of giving Tovorafenib (DAY101) with rituximab. The study will also determine the maximum dose of Tovorafenib (DAY101) that will be used in further studies. To find this dose in a safe way, this study will use a well-established model for dose increases which will help decide whether the dose should go up, stay the same, or go down for future participants, based on how people in the study are responding. In this portion of the study, you will get the study drug Tovorafenib (DAY101) in combination with a drug called rituximab which is currently used routinely in the treatment of hairy cell leukemia. You will get Tovorafenib (DAY101) as a pill once per week for 16 weeks. You will also get rituximab through a vein in your arm on the first day of weeks 5 through 9, and again on the first day of weeks 11, 13, and 15. You will receive study treatment for approximately 26 weeks. Part 2: The purpose of this study is to compare the effectiveness of a drug called Tovorafenib (DAY101) against the effectiveness of a drug called cladribine when used in the treatment of hairy cell leukemia. This part of the study will be divided into two groups, and you will be assigned to one of the groups. • Group 1: If you are in this group, you will be treated using the usual approach used to treat this type of cancer. You will get cladribine through a vein in your arm the first 5 days of the study. You will also get rituximab through a vein in your arm on the first day of weeks 5 through 12. This study lasts 26 weeks. • Group 2: If you are in this group, you will get Tovorafenib (DAY101) plus the usual drug used to treat this type of cancer, rituximab. You will get Tovorafenib (DAY101) as a pill once per week for 16 weeks. You will also get rituximab through a vein in your arm on the first day of weeks 5 through 9, 11, 13, and 15. Study-related procedures that are being done beyond your standard of care will be provided at no cost to you or your insurance. Additional information can be found here: https://clinicaltrials.gov/study/NCT06965114 [email protected]