Pre-emptive Therapy With DEC-C to Improve Outcomes in MDS Patients With Measurable Residual Disease Post Allogeneic Hematopoietic Cell Transplant

NCT ID: NCT04742634

Last Updated: 2025-11-25

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 209 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-12
• Study Completion Date: 2033-11-30

Brief 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.

Conditions

Myelodysplastic Syndromes

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase I Dose Level 1: DEC-C

• 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.
• 35 mg decitabine/100 mg cedazuridine taken by mouth once daily on Days 1, 2, 3 of a 28 day cycle.

Group Type: EXPERIMENTAL

DEC-C

Intervention Type: DRUG

• DEC-C will be provided by Taiho Pharmaceuticals.
• Cycle 1 Day 1 may take place between Day 42 & Day 100 post-transplant.

MyeloSeq-HD

Intervention Type: DEVICE

-Laboratory test developed at Washington University School of Medicine

Phase I Dose Level 2: DEC-C

• 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.
• 35 mg decitabine/100 mg cedazuridine taken by mouth once daily on Days 1-4 of a 28 day cycle.

Group Type: EXPERIMENTAL

DEC-C

Intervention Type: DRUG

• DEC-C will be provided by Taiho Pharmaceuticals.
• Cycle 1 Day 1 may take place between Day 42 & Day 100 post-transplant.

MyeloSeq-HD

Intervention Type: DEVICE

-Laboratory test developed at Washington University School of Medicine

Phase II MRD Positive: DEC-C

• 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.
• 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.

Group Type: EXPERIMENTAL

DEC-C

Intervention Type: DRUG

• DEC-C will be provided by Taiho Pharmaceuticals.
• Cycle 1 Day 1 may take place between Day 42 & Day 100 post-transplant.

MyeloSeq-HD

Intervention Type: DEVICE

-Laboratory test developed at Washington University School of Medicine

Phase II MRD Negative: Observation Arm

• 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.
• 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

Group Type: ACTIVE_COMPARATOR

MyeloSeq-HD

Intervention Type: DEVICE

-Laboratory test developed at Washington University School of Medicine

Interventions

DEC-C

• DEC-C will be provided by Taiho Pharmaceuticals.
• Cycle 1 Day 1 may take place between Day 42 & Day 100 post-transplant.

Intervention Type: DRUG

MyeloSeq-HD

-Laboratory test developed at Washington University School of Medicine

Intervention Type: DEVICE

Other Intervention Names

decitabine + cedazuridine; ASTX727; INQOVI®

Eligibility Criteria

Inclusion Criteria

Eligibility Criteria for MyeloSeq-HD Assay (Step 1)

• Diagnosis of myelodysplastic syndromes (MDS) based on World Health Organization classification (2016 revision) who have received an allogeneic hematopoietic cell transplant. Any stem cell source, conditioning regimen, and immunosuppression regimen as determined by the treating physician, per institutional guidelines, is permitted. Patients may have received any therapy, or no therapy, prior to transplant.
• 18 to 75 years of age.
• Must have undergone gene panel testing prior to the start of transplant conditioning and must have at least one somatically acquired mutation that is interrogated by the MyeloSeq-HD panel. If the patient has a variant that is known to be a germline/inherited myeloid predisposition gene in that patient, this variant cannot and will not be used as evidence of MRD positivity. If the pre-transplant gene panel testing is a next-generation sequencing panel other than the MyeloSeq platform, the outside report will be reviewed by the PI and the molecular pathologists at the McDonnell Genome Institute to ensure eligibility.
• Willing to comply with the treatment assignment:

• Intent to proceed with DEC-C therapy if one or more variants detected prior to transplant persists at Day 30 post-transplant with a variant allele frequency of ≥ 0.2%.
• Not currently receiving any investigational agents.
• Ability to understand and willingness to sign an IRB-approved written informed consent document (or that of legally authorized representative, if applicable).

• One or more somatically acquired variants that were present prior to transplant detected by the MyeloSeq-HD panel at Day 30 post-transplant, with a variant allele frequency of ≥ 0.2%
• Within Days 42-100 post-transplant.
• ≤ 5 % bone marrow myeloblasts on the Day 30 post-transplant biopsy.
• Absolute neutrophil count (ANC) ≥ 1.0 X 109/L and platelets ≥ 50 X 109/L.
• Only patients with adequately controlled GVHD ≤ Grade 2 are eligible for the DEC-C intervention arm. Patients with active grade 3 or higher GVHD are ineligible for the DEC-C intervention arm.
• ECOG performance status ≤ 2
• Adequate renal and hepatic function as described below:

• Total bilirubin ≤ 1.5 x IULN
• AST(SGOT)/ALT(SGPT) ≤ 3.0 IULN
• Creatinine clearance ≥ 30 mL/min using Cockcroft-Gault Formula below:

CrCl = [(140-age) x body weight in kg]/(serum creatinine in mg/dL x 72) x 0.85 if female

*NOTE: If, in the opinion of the treating physician, bilirubin is elevated secondary to hemolysis or Gilbert's disease, the patient may be eligible after discussion with the Washington University PI

• Decitabine has been shown to be teratogenic in animal studies and use of IV decitabine in the first trimester of pregnancy has been associated with major birth defects. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Men and women treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of the study, and 6 months after completion of the study.

• EITHER ≤ 5 % bone marrow myeloblasts on the Day 30 post-transplant biopsy OR enrolled in the study with > 5% bone marrow myeloblasts on the Day 30 post-transplant biopsy but not meeting eligibility criteria for the intervention arm.
• Not receiving any investigational agents.

Exclusion Criteria

• Currently receiving any other investigational agents.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to DEC-C or other agents used in the study.
• Concomitant administration of drugs metabolized by cytidine deaminase
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum/urine pregnancy test no more than 10 days prior of the start of the first cycle of DEC-C.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Taiho Oncology, Inc.

INDUSTRY

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Meagan Jacoby, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Meagan Jacoby, M.D., Ph.D.

Role: CONTACT

mjacoby@wustl.edu

314-747-8465

Facility Contacts

Meagan Jacoby, M.D., Ph.D.

Role: primary

mjacoby@wustl.edu

314-747-8465

Related Links

http://www.siteman.wustl.edu

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Other Identifiers

202103255

Identifier Type: -

Identifier Source: org_study_id