NCT05528354

Venetoclax and Decitabin Based Conditioning Regimen Followed With Post-HSCT Decitabin Maintenance Therapy in TP53 Mutant AML/MDS Patients

• Status: Unknown
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 58 (estimated)
• Sponsor: Zhejiang University · Academic / Other
• Sex: All
• Age: 12 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

This study aims to evaluate the effectiveness and safety of Venetoclax and Decitabin based conditioning regimen followed with post-HSCT Decitabin maintenance therapy in TP53 mutant AML/MDS Patients.

Detailed description

In acute myeloid leukemia and myelodysplastic syndromes, TP53 gene mutation is a poor prognostic factor and a strong indication for hematopoietic stem cell transplantation. However, because of the high relapse rate of myeloid tumors with TP53 mutation, new comprehensive treatment is urgently needed to improve the efficacy of transplantation. Decitabin(DEC) has shown certain efficacy in primary patients with TP53 mutation, and Venetoclax (VEN) and DEC have synergistic effect. Based on this, we hypothesized that DEC and VEN should be added to the conditioning regimen in TP53 mutant AML/MDS patients in order to eliminate malignant clones with P53 mutation as much as possible, and intermittent DEC maintenance therapy should be used to prevent relapse after post-HSCT hematopoietic reconstruction. We intend to conduct a multicenter, single-arm clinical study to evaluate the efficacy and safety of this protocol.

Conditions

• Hematopoietic Stem Cell Transplantation
• TP53

Interventions

Type	Name	Description
DRUG	VEN and DEC based conditioning regimen	Patients with age\<50 years and HCT-CI\<3: Haploidentical transplantation: AraC 2g/m2 d-10\~d-9, BU 0.8mg/kg q6h d-8\~-6, CTX 1.8g/m2 d-5\~d-4, Meccnu 250mg/m2 d-3, ATG 1.5mg/kg/d d-5\~-2, VEN 400mg/d d-15\~-9, DEC 20mg/m2 d-15\~-11; HLA-matched transplantation: BU 0.8mg/kg q6h d-7\~-4, CTX 60mg/kg d-3\~d-2, Meccnu 250mg/m2 d-1, VEN d-12\~-8, DEC 20mg/m2 d-12\~-6, and ATG for the unrelated donor type. Patients with age\>50 years or HCT-CI≥3: Flu 30mg/m2 d-10\~-5, BU 0.8mg/kg q6h d-7\~-5, Meccnu 250mg/m2 d-4, ATG 7.5mg/kg divided into d-4\~-1, VEN d-15\~-9, DEC 20mg/m2 d-15\~-11. Note: if Voriconazole or Posaconazole is used to prevent or treat fungal infections, VEN should be 200mg/d for 7 consecutive days.
DRUG	DEC	In the time window of 60-120 days after transplantation: DEC 5mg/m2/d for 5 consecutive days every 6 to 8 weeks with a total of 4 to 6 courses if there is no severe aGVHD (grade 3 or higher) and the donor chimerism rate of bone marrow blood (STR)\>95%. If the MRD turns positive, DLI can be performed.

Timeline

• Start date: 2022-06-02
• Primary completion: 2025-12-31
• Completion: 2025-12-31
• First posted: 2022-09-06
• Last updated: 2022-09-06

Locations

1 site across 1 country: China