NCT04742634 · Washington University School of Medicine
Pre-emptive Therapy With DEC-C to Improve Outcomes in MDS Patients With Measurable Residual Disease Post Allogeneic Hematopoietic Cell Transplant
What this study is about
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).
View original scientific description
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
DRUG
DEC-C
* DEC-C will be provided by Taiho Pharmaceuticals. * Cycle 1 Day 1 may take place between Day 42 \& Day 100 post-transplant.
DEVICE
MyeloSeq-HD
-Laboratory test developed at Washington University School of Medicine
Primary outcome measures
Number of patients with dose-limiting toxicities (Phase I only)
Time frame: Completion of cycle 1 (each cycle is 28 days) for all phase I participants (estimated to be 13 months)
-Dose-limiting toxicities (DLTs) are defined as any of the following adverse events that occur during the DLT observation period (Cycle 1) during the phase I portion of the study, determined to be possibly, probably, or definitely related to the study drug: * Grade 4 neutropenia or grade 4 thrombocytopenia in the absence of increased blasts and/or evidence of persistent MDS at the end of Cycle 1. * Any grade 3 or higher non-hematologic toxicity except for grade 3 vomiting or diarrhea not requiring tube feeding, total parenteral nutrition, or requiring or prolonging hospitalization, or grade 3 or 4 isolated electrolyte abnormalities that last \<72 hours. * Any other non-hematologic toxicity that is clinically significant and/or unacceptable that does not respond to supportive care, results in disruption of dosing schedule more than 28 days, or is judged to be a DLT by the Investigator. * Confirmed Hy's law cases will be considered a DLT
Maximum tolerated dose (MTD) (Phase I only)
Time frame: Completion of cycle 1 (each cycle is 28 days) for all phase I participants (estimated to be 13 months)
-The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which ≥ 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity during the first cycle.
Recommended phase II dose (Phase I only)
Time frame: Completion of cycle 1 (each cycle is 28 days) for all phase I participants (estimated to be 13 months)
-The recommended phase II dose will be less than or equal to the maximum tolerated dose
Progression-free survival (PFS) (Phase II recommended dose only)
Time frame: 1 year post-transplant
-Progression-free survival: Defined as the interval from the date of transplant to disease progression or death, whichever is first. Patients without documented disease progression or death at the time of analysis will be censored at the date of last adequate tumor assessment.
Rate of relapse (Phase II recommended dose only)
Time frame: 1 year post-transplant
-Disease progression/relapse post-transplant is defined as \>5% myeloblasts in the bone marrow, evidence of extramedullary disease, reemergence of pre-transplant cytogenetic abnormalities, or intervention by the treating physician (such as withdrawal of immunosuppression) for reemergence of pre-transplantation morphologic abnormalities that are likely relapsed disease in the opinion of the treating physician. Censoring rules for the Relapse endpoint include: Patients who do not relapse will be censored at the date of last disease assessment where no relapse was documented; Patients who die without relapse will be censored at the date of death if no relapse was observed prior to death. Patients who withdraw consent or are lost to follow-up will be censored at the date of last disease assessment showing no evidence of relapse; Patients who start a new anti-cancer therapy before documented relapse will be censored at the date of last disease assessment before the start of the new therapy.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- are not met.
- 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). Eligibility Criteria for Step 2 Step 2A 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 ≥ 0.2%
- 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. Step 2B Inclusion Criteria (Observation Arm)
- 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. Step 2A
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.
Where
- St Louis, Missouri
Collaborators
Taiho Oncology, Inc.
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Mar 23, 2026 · Source of record for eligibility and locations