Stem Cell Transplantation for Blood Cancer

This trial explores how personalized doses of chemotherapy and supportive care medications might improve survival rates for individuals with blood cancer caused by changes in the RUNX1 gene. Participants will undergo stem cell transplants, with different groups receiving specific drug combinations, including Busulfan, Cyclophosphamide, and Fludarabine (all chemotherapy drugs), and possibly radiation (Total Body Irradiation) to prepare for the transplant. The trial seeks individuals with blood cancer linked to the RUNX1 gene mutation, as well as stem cell donors and healthy volunteers. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

The trial protocol does not specify if you need to stop taking your current medications. However, since the trial involves chemotherapy and supportive care tailored to each participant, it's possible that adjustments to your current medications might be necessary. It's best to discuss your specific situation with the trial team.

A previous study showed that using a combination of busulfan and cyclophosphamide for stem cell transplants reduced severe acute GVHD, a condition where donor cells attack the recipient. However, this combination can be more toxic, potentially causing more unwanted side effects. Another study found no deaths related to the transplant itself, indicating a positive safety profile.

In contrast, when fludarabine, cyclophosphamide, and total body irradiation were used together, most participants tolerated it well, experiencing no severe side effects. One study reported a 100% survival rate at a median follow-up of about 10 months, with many avoiding relapse or GVHD for a year.

Researchers are excited about these treatments for blood cancer because they explore different conditioning approaches before a stem cell transplant. The first approach uses myeloablative conditioning with cyclophosphamide and busulfan, which is designed to aggressively eliminate cancer cells and make room for new, healthy stem cells. The second approach uses a reduced intensity regimen with fludarabine, cyclophosphamide, and total body irradiation, potentially making the treatment less harsh and more suitable for patients who can't tolerate intense treatments. These innovative strategies offer hope for improved outcomes and patient suitability compared to traditional high-dose chemotherapy regimens.

In this trial, participants will join different treatment arms to evaluate the effectiveness of stem cell transplantation for blood cancer. One arm will use a combination of busulfan and cyclophosphamide as a myeloablative conditioning regimen before the introduction of new stem cells. Studies have shown that this method can effectively treat certain blood cancers by preparing the body to accept new stem cells and aiding recovery. Another arm will explore a reduced intensity conditioning regimen using fludarabine, cyclophosphamide, and total body irradiation. This approach is considered gentler, lowering the risk of side effects, and has been linked to better outcomes. Both treatments have shown promise in treating blood cancers, especially in patients with genetic changes like RUNX1.¹⁶⁷⁸⁹