Table of Contents

• Overview of Treosulfan trials
• Conditions being studied
• Trial designs and phases
• Who can take part
• Main outcomes and endpoints
• Key trials at a glance

Overview of Treosulfan trials

The trial data show that Treosulfan is being studied in interventional clinical trials, which means researchers give a treatment and then measure what happens.^[1] Most studies are in the setting of cancer care, especially before or around allogeneic stem cell transplantation, where stem cells come from another person.^[2] One trial studies Treosulfan in Ewing Sarcoma, while many others focus on blood cancers such as AML, MDS, ALL, CLL, and myelofibrosis.^[1][3]

Several studies compare Treosulfan-based treatment with another conditioning plan, while others test it as part of a combination regimen.^{[2][4] The main goal is to learn whether these plans are safe, feasible, and effective for the target patient groups.[1][5]}

Conditions being studied

The trials cover a wide range of diseases, but most are in blood cancers and transplant-related care.^{[2][3] The main conditions include acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), chronic myelomonocytic leukemia (CMML), myelofibrosis, and secondary AML.[2][3][4]}

One study is in children with autosomal recessive osteopetrosis caused by TCIRG1 gene mutations, which is a rare inherited bone disease.^[6] Another study focuses on newly diagnosed high-risk and very high-risk Ewing Sarcoma, a cancer that usually starts in bone or soft tissue.^[1]

Trial designs and phases

Most Treosulfan studies are in Phase 2 or Phase 3, which are later trial stages used to study effectiveness and safety in larger groups.^{[1][2][3] There is also a Phase 1 study that mainly looks at safety and the best way to combine treatments, and a Phase 1/2 study in children with osteopetrosis.[6][7]}

Some trials are randomized, meaning patients are assigned to one treatment group or another by chance.^{[2][4] Others are open-label, which means both the researchers and the participants know which treatment is being used.[6] One large Phase 4 platform trial includes several linked sub-studies in children and young adults with acute lymphoblastic leukemia.[8]}

Who can take part

Eligibility depends on the disease and the treatment plan in each trial.^{[1][2] Some studies include children and adolescents, such as the Ewing Sarcoma trial, the osteopetrosis study, and the ALL transplant trial.[1][6][8]}

Other studies are for adults, including people aged 40 to under 65 years with AML, elderly patients with AML or MDS, and adults with high-risk MDS, CMML, or secondary AML before transplant.^{[5][7][9] Some trials require a planned allogeneic hematopoietic cell transplant or a specific disease status such as first or second complete remission, which means the cancer is under control after treatment.[2][5]}

Main outcomes and endpoints

The trials measure different outcomes depending on the study question.^{[1][2] Common endpoints include overall survival, event-free survival, and leukemia-free survival, which show how long patients live or stay free from major problems after treatment.[2][5][7]}

Several studies also measure transplant-related outcomes such as graft-versus-host disease, rejection, relapse, graft failure, and second cancers.^{[4][8] Safety is often measured by the number and severity of adverse effects and serious adverse effects, sometimes using CTCAE grading, which is a standard way to rate side effects in trials.[1][9]}

Some studies use more specific endpoints, such as minimal residual disease negativity in AML, undetectable MRD in CLL, or disease- and rejection-free survival after transplant.^{[3][4][10] The Ewing Sarcoma study measures both safety and 36-month event-free survival.[1]}

Key trials at a glance

• Ewing Sarcoma study — a Phase 2 multicenter trial in 60 patients, testing Treosulfan/Melphalan as consolidation treatment and measuring adverse effects and 36-month event-free survival.^[1]
• RELEVANT — a Phase 2 randomized study in AML and MDS transplant patients, comparing Treosulfan with melphalan conditioning and measuring overall survival.^[2]
• Myelofibrosis haplo-identical transplant trial — a Phase 2 study in 28 patients, looking at disease- and rejection-free survival 12 months after transplant.^[4]
• AML and MDS GVHD prevention study — a Phase 3 trial in 324 patients, comparing two graft-versus-host disease prevention strategies after fludarabine-Treosulfan conditioning.^[3]
• ALL FORUM trial — a large Phase 4 study in children and young people with ALL, with Treosulfan as one of the conditioning options and overall survival or event-free survival as key outcomes.^[8]