Clinical trial NCT04742634: Pre-emptive Therapy With DEC-C to Improve Outcomes in MDS Patients With Measurable Residual Disease Post Allogeneic Hematopoietic Cell Transplant
Official title: A Phase I/II Trial of Pre-emptive Therapy With DEC-C to Improve Outcomes in MDS Patients With Measurable Residual Disease Post Allogeneic Hematopoietic Cell Transplant
Conditions: Myelodysplastic Syndromes
Summary: The investigators hypothesize that early measurable residual disease (MRD)-guided pre-emptive therapy with decitabine + cedazaridine (DEC-C) will decrease the risk of progression in post-transplant myelodysplastic syndromes (MDS) patients with persistent mutations (molecular MRD). To detect molecular MRD, the investigators will perform ultra-deep, error-corrected panel-based sequencing (MyeloSeq-HD) at Day 30 in post-transplant MDS patients. The investigators will treat patients with detectable molecular MRD with DEC-C to determine if pre-emptive, MRD-guided therapy with DEC-C decreases relapse rates and improves progression-free survival.
Interventions:
description: * DEC-C will be provided by Taiho Pharmaceuticals.<br/>* Cycle 1 Day 1 may take place between Day 42 & Day 100 post-transplant.
name: DEC-C
other_name: ASTX727
INQOVI®
decitabine + cedazuridine
type: Drug
description: -Laboratory test developed at Washington University School of Medicine
name: MyeloSeq-HD
type: Device
Study arms:
design_group_description: * Bone marrow biopsy & MyeloSeq-HD will be obtained on Day 30 post-transplant. MRD positivity is defined as the presence of at least one somatically acquired mutation detected prior to transplant that persists at Day 30 post-transplant with a variant allele frequency of ≥ 0.2%. MRD-positive patients will receive up to 5 cycles of DEC-C prior to the Day 180 bone marrow evaluation. If the Day 180 MyeloSeq-HD shows that MRD is still detectable in the opinion of the MGI board-certified molecular pathologist but below 0.5% and patient has tolerated initial treatment without toxicity, the patient may continue treatment. If it shows a lack of MRD, the patient will be moved to the post-treatment surveillance arm. If it shows any mutation detection prior to transplant that persists with a variant allele frequency of ≥ 0.2%VAF, the patient will receive up to an additional 6 cycles of DEC-C.<br/>* 35 mg decitabine/100 mg cedazuridine taken by mouth once daily on Days 1, 2, 3 of a 28 day cycle.
design_group_title: Phase I Dose Level 1: DEC-C
design_group_type: Experimental
design_group_description: * Bone marrow biopsy & MyeloSeq-HD will be obtained on Day 30 post-transplant. MRD positivity is defined as the presence of at least one somatically acquired mutation detected prior to transplant that persists at Day 30 post-transplant with a variant allele frequency of ≥ 0.2%. MRD-positive patients will receive up to 5 cycles of DEC-C prior to the Day 180 bone marrow evaluation. If the Day 180 MyeloSeq-HD shows that MRD is still detectable in the opinion of the MGI board-certified molecular pathologist but below 0.5% and patient has tolerated initial treatment without toxicity, the patient may continue treatment. If it shows a lack of MRD, the patient will be moved to the post-treatment surveillance arm. If it shows any mutation detection prior to transplant that persists with a variant allele frequency of ≥ 0.2%VAF, the patient will receive up to an additional 6 cycles of DEC-C.<br/>* 35 mg decitabine/100 mg cedazuridine taken by mouth once daily on Days 1-4 of a 28 day cycle.
design_group_title: Phase I Dose Level 2: DEC-C
design_group_type: Experimental
design_group_description: * 35 mg decitabine/100 mg cedazuridine taken by mouth once daily per the schedule determined in the Phase I portion of the study. Cycle 1 Day 1 may take place between Day 42 and Day 100 post-transplant. MRD-positive patients will receive up to 5 cycles of DEC-C prior to the Day 180 bone marrow evaluation.<br/>* Bone marrow biopsy with MyeloSeq-HD will be obtained on Day 180 post-transplant. If the Day 180 MyeloSeq-HD shows that MRD is still detectable in the opinion of the MGI board-certified molecular pathologist but below 0.5% and patient has tolerated initial treatment without toxicity, the patient may continue treatment. If it shows a lack of MRD, the patient will be moved to the post-treatment surveillance arm. If it shows any mutation detection prior to transplant that persists with a variant allele frequency of ≥ 0.2%VAF, the patient will receive up to an additional 6 cycles of DEC-C.
design_group_title: Phase II MRD Positive: DEC-C
design_group_type: Experimental
design_group_description: * In phase II, up to 77 patients who do not have MRD positivity on Day 30 post-transplant (i.e., the absence of at least one somatically acquired mutation detected prior to transplant that persists at Day 30 post-transplant with a variant allele frequency of ≥ 0.2%) will be placed on the observation arm and treated with standard of care.<br/>* Patients on the observation arm will be followed every 3 months for 2 years and every 6 months for 3 years for progression and survival
design_group_title: Phase II MRD Negative: Observation Arm
design_group_type: Active Comparator
Sponsor: Washington University School of Medicine
Collaborators: Taiho Oncology, Inc.
Drug name mappings:
name: 地西他滨/西达尿苷
lang: CN
name: Decitabine/Cedazuridine
lang: EN