NCT06532084

Sorafenib Relapase Prophylaxis After HCT With PTBCy Regimen

Randomized Trial of Sorafenib Prophylaxis After Allogeneic Hematopoietic Stem Cell Transplantation With Post-transplantation Bendamustine and Cyclophosphamide

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 88 (estimated)
• Sponsor: St. Petersburg State Pavlov Medical University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This is a single-center randomized open-label phase II clinical trial to compare relapse prophylaxis with sorafenib and observation after graft-versus-host disease prophylaxis with post-transplantation bendamustine and cyclophosphamide in high-risk myeloid malignancies. This is an intention to treat study, where randomization is performed at first documentation of CR after engraftment.

Detailed description

Allogeneic hematopoietic stem cell transplantation (HCT) results steadily improve due to reduction of NRM. Standard risk patients now have the risk of HCT below 10% after matched donor transplantation. Nonetheless, there is limited improvement in CIR over time. Especially novel strategies to reduce relapse are needed for high-risk myeloid malignancies where standard HCT approaches result in relatively unfavorable outcomes. Among high-risk malignancies are refractory AML without hematological remission for HCT. In this group EFS rarely exceeds 15%. Some improvement in refractory AML was reported with intensified sequential conditioning regimens, but there use is limited to young and fit patients who comprise only around 20-30% of all refractory AML population. Also it was demonstrated that AML patients beyond CR2 have significantly worse prognosis than CR1 and CR2 patients. It is reported that long-term EFS in this group of patients is around 30%. The next adverse group of HCT recipients are patients with high-risk somatic mutations. It is reported in several studies that EFS in tp53-mutant AML even allografted in CR is 0%. Another adverse mutation is ASXL1, where also 0-10% EFS was demonstrated in large cohorts of patients. For therapy related myeloid malignancies it was also demonstrated that the CIR is higher and this group patients have even in CR have 30% EFS. Complex karyotype and monosomal karytope, involvement of chromosome 3 with EVI1 gene, which are common in this patients group, further exacerbate prognosis. Very high risk MDS was also reported to have dismal prognosis after allogeneic HCT. All these adverse groups were included in the study. PTBCy GVHD prophylaxis provides augmented GVL and better disease control in high-risk myeloid malignancies, but GVL effect fades over time. While median relapse rate is significantly prolonged to 8 months against the previously reported in the literature 2-3 months, the relapse rate with long term follow up remains high. Thus this longer time to relapse gives enough time to initiate sorafenib prophylaxis which was shown to be one of the most promising agents for relapse prophylaxis. Given its immune modulatory properties the study hypothesis is that sorafenib with PTBCy GVHD prohylaxis will further augment GVL and facilitate better disease control.

Conditions

• Acute Myeloid Leukemia, in Relapse
• Myelodysplastic Syndromes
• Chronic Myeloid Leukemia
• Myeloproliferative Neoplasm

Interventions

Type	Name	Description
DRUG	Sorafenib	Sorafenib 200 mg bid for 168 days starting in the time fram between engraftment with neutrophils \> 1.0 x 10\^9/L, white blood cells\> 1.5 x 10\^9/L, platelets\> 1.5 x 10\^9/L and day+100 after allogeneic hematopoietic cell trnaplantation

Timeline

• Start date: 2024-05-22
• Primary completion: 2027-05-01
• Completion: 2028-05-01
• First posted: 2024-08-01
• Last updated: 2024-08-01

Locations

1 site across 1 country: Russia