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DNA Methyltransferase Inhibitor

DEC-C Pre-emptive Therapy for Myelodysplastic Syndrome

Phase 1 & 2

Recruiting

Led By Meagan Jacoby, M.D., Ph.D.

Research Sponsored by Washington University School of Medicine

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Inclusion Criteria DEC-C Intervention Arm: 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 ≥ 0.5% Within Days 42-100 post-transplant. 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.

At least 18 years of age.

Must not have

Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.

Concomitant administration of drugs metabolized by cytidine deaminase

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1 year post-transplant

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing whether a treatment of decitabine and cedazaridine (DEC-C) can decrease the risk of progression in post-transplant myelodysplastic syndromes (MDS) patients with persistent mutations (molecular MRD). To detect molecular MRD, the investigators will use MyeloSeq-HD sequencing 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.

Who is the study for?

Adults diagnosed with myelodysplastic syndromes who have had a stem cell transplant. They must have specific mutations detectable by MyeloSeq-HD, stable mild GVHD (if present), good kidney and liver function, and agree to use contraception. Excluded are pregnant or breastfeeding individuals, those on certain drugs, or with uncontrolled illnesses.

What is being tested?

The trial tests if early treatment with DEC-C can prevent disease progression in MDS patients post-transplant showing persistent mutations via MyeloSeq-HD testing. It aims to see if this approach lowers relapse rates and improves survival without the disease getting worse.

What are the potential side effects?

DEC-C may cause side effects similar to other chemotherapy agents such as nausea, fatigue, low blood counts leading to increased infection risk, liver issues, and potential harm to an unborn child.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 18 years old or older.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have any serious illnesses like heart failure or uncontrolled infections.

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I am taking medication that affects my body's enzyme levels.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 1 year post-transplant

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~1 year post-transplant

This trial's timeline: 3 weeks for screening, Varies for treatment, and 1 year post-transplant for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Maximum tolerated dose (MTD) (Phase I only)

Number of patients with dose-limiting toxicities (Phase I only)

Progression-free survival (PFS) (Phase II recommended dose only)

+2 more

Secondary study objectives

Neoplasm, Residual

Overall survival (OS)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

4Treatment groups

Experimental Treatment

Active Control

Group I: Phase II MRD Positive: DEC-CExperimental Treatment2 Interventions

* 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 ≥ 0.5%VAF, the patient will receive up to an additional 6 cycles of DEC-C.

Group II: Phase I Dose Level 2: DEC-CExperimental Treatment2 Interventions

* 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 ≥ 0.5%. 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 ≥ 0.5%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 III: Phase I Dose Level 1: DEC-CExperimental Treatment2 Interventions

Group IV: Phase II MRD Negative: Observation ArmActive Control1 Intervention

* 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 ≥ 0.5%) 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

0 / 4Eligibility criteria met