The Gut Microbiome in FLT3- AL Undergoing Allo-HSCT With Or Without Sorafenib Maintenance

Nanfang Hospital, Southern Medical University

Status: Enrolling

Conditions: Allogeneic Hematopoietic Stem Cell Transplantation; Acute Leukemia

Treatments: Drug: Sorafenib

Study type: Observational

Funder types: Other

Identifiers

NCT05601895

Microbiota-Sora-FLT3-AL-2022

Details and patient eligibility

About

This prospective trial investigates the effect of sorafenib maintenance therapy in FLT3 negative acute leukemia patients after allo-HSCT in terms of gut microbiome.

Full description

Acute leukemia is a heterogeneous group of clonal diseases. Leukemia relapse remains the main cause of treatment failure, including the patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Sorafenib, an inhibitor of multiple kinases including FLT3, has shown promising activity in FLT3-ITD-positive AML. The investigator's previous studies demonstrated that sorafenib maintenance post-transplantation could improve the outcomes of FLT3-ITD positive AML patients, which was associated with sorafenib enhancing the graft-versus-leukemia (GVL) effect. Recent studies have shown that sorafenib is also effective in patients with FLT3-negative acute leukemia. The investigator's previous exploratory study found that salvage therapy such as sorafenib combined with chemotherapy and donor lymphocyte infusion could significantly improve the CR rate and survival in patients with recurrent FLT3-negative acute leukemia after allo-HSC. More and more studies have shown that sorafenib and allo-HSCT have synergistic GVL effect. Some studies have demonstrated that gut microbiome is associated with graft-versus-host-disease (GVHD) and GVL. However, the exact mechanism of sorafenib enhancing the GVL effect and the influence of gut microbiome on sorafenib maintenance after allo-HSCT in FLT3 negative acute leukemia patients remain unknown.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• FLT3 Negative Acute Leukemia
• Allo-HSCT Recipients

Exclusion criteria

• intolerance to sorafenib pretransplantation
• cardiac dysfunction (particularly congestive heart failure)
• hepatic abnormalities (bilirubin ≥ 3 mg/dL, aminotransferase> 2 times the upper limit of normal)
• renal dysfunction (creatinine clearance rate < 30 mL/min)
• Any abnormality in a vital sign (e.g., heart rate, respiratory rate, or blood pressure)
• Patients with any conditions not suitable for the trial (according to the investigators' decision)

Trial design

60 participants in 2 patient groups

sorafenib group

Description:

FLT3- acute leukemia patients who receive sorafenib maintenance therapy after allo-HSCT. Sorafenib will be used from day 30 to 180 post-transplantation. The initial dose of sorafenib is 400 mg orally twice daily and is adjusted in case of suspected toxicity or resistance (dose range, 200-800 mg daily).

Treatment:

Drug: Sorafenib

non-sorafenib group

Description:

FLT3- acute leukemia patients who do not receive sorafenib maintenance therapy after allo-HSCT.