Low Dose ASTX727 for Myelodysplastic Syndrome

Not currently recruiting at 45 trial locations

Overseen By Astex Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Taiho Oncology, Inc.

Must not be taking: Azacitidine, Decitabine, Guadecitabine

Disqualifiers: Chronic myelomonocytic leukemia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to test a new drug, ASTX727 LD (a low-dose chemotherapy treatment), for individuals with Myelodysplastic Syndrome (MDS), a condition where the bone marrow fails to produce enough healthy blood cells. The goal is to determine the safety and effectiveness of various doses of this treatment. Participants will be divided into groups to receive different doses and schedules to observe their body's response. The trial seeks individuals diagnosed with MDS who require regular red blood cell transfusions or have low blood counts. As a Phase 1/Phase 2 trial, this research focuses on understanding the treatment's function in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial requires that any treatments for myelodysplastic syndrome (MDS) must be stopped at least 1 month before starting the study treatment. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

Is there any evidence suggesting that ASTX727 LD is likely to be safe for humans?

Research has shown that low-dose ASTX727 is generally safe for people with lower-risk myelodysplastic syndromes (MDS). Studies have found that a 5-day treatment plan is usually well-tolerated, with most people not experiencing severe side effects. Reports indicate fewer cases of neutropenia, a drop in white blood cells, with this treatment, which is a positive sign. Overall, the treatment appears to be a safe option for patients with this condition. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for myelodysplastic syndrome?

Researchers are excited about ASTX727 LD for myelodysplastic syndrome because it offers a novel approach to treatment. Unlike standard therapies, which often involve separate drugs for DNA methylation inhibition and cytotoxic effects, ASTX727 LD combines these actions in a single oral medication. This dual-action mechanism could simplify treatment regimens and improve patient compliance, as it may offer more consistent dosing and fewer side effects. Additionally, its oral administration is a significant advantage over traditional intravenous treatments, improving convenience for patients.

What evidence suggests that ASTX727 LD might be an effective treatment for Myelodysplastic Syndrome?

Research has shown that ASTX727 LD might benefit people with low-risk myelodysplastic syndromes (MDS). In one study, about 30% of patients experienced improved blood cell counts, and 33% did not require red blood cell transfusions for at least 8 weeks. The treatment appears manageable and may work well over time, with a reduced risk of causing low white blood cell counts. These findings suggest ASTX727 LD could be a promising option for individuals with this type of MDS. Participants in this trial will enroll in different phases to evaluate the effectiveness and safety of ASTX727 LD at various dosages. ^{1 2 3 4 6}

Who Is on the Research Team?

Yuri Sano, MD, PhD

Principal Investigator

Astex Pharmaceuticals, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with low-risk or Intermediate-1 Myelodysplastic Syndrome who have specific blood count criteria, can follow study procedures, and are not pregnant. They must agree to use birth control during and after the trial. People with certain other conditions or treatments, like recent investigational drugs or prior malignancies (with some exceptions), cannot join.

Inclusion Criteria

Able to understand and comply with the study procedures, understand the risks involved in the study, and provide written informed consent before the first study-specific procedure

Subjects must have had at least 1 of the following disease-related criteria during the 8 weeks before randomization: Red blood cell (RBC) transfusion dependence of 2 or more units of RBC transfusions, Hb of <9.0 g/dL in at least 2 blood counts prior to randomization or in 1 blood count if RBC transfusion was received, Absolute Neutrophil Count (ANC) of <0.5 × 10^9/L in at least 2 blood counts prior to randomization, Platelet counts of <50 × 10^9/L in at least 2 blood counts prior to randomization, Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, Adequate organ function, Women of child-bearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening, Women of child-bearing potential must agree to use contraceptive measures of birth control for 6 months after completing treatment; men must use contraceptive measures and agree not to father a child for at least 3 months after completing treatment

I am 18 or older with low to intermediate-1 risk MDS.

Exclusion Criteria

I do not have an active HIV or hepatitis infection.

I have been treated with azacitidine, decitabine, or guadecitabine before.

I haven't taken any experimental drugs in the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Stage A

Subjects are randomized into 3 cohorts of 6 subjects each testing different doses of oral decitabine with cedazuridine in 28-day cycles

28 days per cycle

Phase 1 Stage B

Additional 30 subjects randomized in a 1:1:1 ratio into 3 cohorts of 10 subjects in 28-day cycles

28 days per cycle

Phase 2

80 additional subjects randomized in a 1:1 ratio studying two different doses/schedules

18-24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ASTX727 LD

Trial Overview The study tests different doses of ASTX727 LD in people with MDS over two phases: Phase 1 randomizes participants into three groups for a 28-day cycle; Phase 2 involves 80 new subjects split evenly between two dose schedules to evaluate safety and effectiveness.

How Is the Trial Designed?

Group I: Phase 2 Experimental Treatment 2 Interventions

80 additional subjects randomized in a 1:1 ratio studying two different doses

Group II: Phase 1 Stage B Experimental Treatment 1 Intervention

3 cohorts of 10 subjects each in 28-day cycles of ASTX727 LD

Group III: Phase 1 Stage A Experimental Treatment 1 Intervention

3 cohorts of 6 subjects each in a schedule in 28-day cycles of ASTX727 LD

Who Is Running the Clinical Trial?

Taiho Oncology, Inc.

Lead Sponsor

Trials

79

Recruited

12,700+

Tim Whitten

Taiho Oncology, Inc.

Chief Executive Officer since 2018

MBA and Pharmacy degree

Harold Keer

Taiho Oncology, Inc.

Chief Medical Officer

MD, PhD

Astex Pharmaceuticals, Inc.

Lead Sponsor

Trials

97

Recruited

7,400+

Dr. Harren Jhoti

Astex Pharmaceuticals, Inc.

Chief Executive Officer since 2007

PhD in Biochemistry from Birkbeck College, London

Dr. Harold N. Keer

Astex Pharmaceuticals, Inc.

Chief Medical Officer since 2020

MD

Published Research Related to This Trial

In lower-risk myelodysplastic syndromes (MDS) patients, erythropoiesis stimulating agents (ESAs) can improve survival, and decision tools help determine the best initial treatment approach, whether with ESAs or other therapies.

For higher-risk MDS patients, DNA methyltransferase inhibitors show a response rate of 20% to 30%, and azacitidine has been proven to provide a survival advantage over conventional treatments, marking a significant advancement in therapy options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of MDS: something old, something new, something borrowed... Sekeres, MA.[2018]

Erythropoiesis-stimulating agents (ESAs) like erythropoietin are commonly used as first-line treatments for lower-risk myelodysplastic syndromes (MDS), showing favorable responses in about 50% of patients, although these responses can be short-lived.

New treatments like sotatercept and luspatercept, which inhibit the transforming growth factor (TGF)-β superfamily, offer a promising alternative by stimulating erythroid differentiation and potentially alleviating anemia in patients who do not respond to ESAs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increasing the effectiveness of hematopoiesis in myelodysplastic syndromes: erythropoiesis-stimulating agents and transforming growth factor-β superfamily inhibitors. Mies, A., Platzbecker, U.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10428680/

P719: RANDOMIZED PHASE 1-2 STUDY TO ASSESS ... The Hematologic Improvement (HI) % for all dosing schedules was 30% (14/47), and the RBC transfusion-independent % over 8 weeks was 33% (7/21). Of the 47 ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265023012065

MDS-641 Randomized Phase 1-2 Study to Assess Safety ... This Phase 1/2 study suggests LD-5Day regimen is tolerable (less neutropenia) and potentially an optimal regimen for LR-MDS (longer term efficacy analysis vs ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03502668

NCT03502668 | Phase 1-2 Study of Low Dose ASTX727 ... Multicenter, open-label study of various ASTX727 LD doses and schedules to assess safety, pharmacodynamics, pharmacokinetics, and hematologic response in ...

4. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/4619/499194/Reclassification-of-Ascertain-ASTX727-02

Reclassification of Ascertain (ASTX727-02) Myelodysplastic ... Outcomes including clinical response, overall survival (OS), and leukemia free survival (LFS) based on IPSS-R and IPSS-M scoring systems.

5. astx.com astx.com/2022-ash-astx727-03-phase-1-study-evaluating-oral-decitabine-cedazuridine-astx727-low-dose-ld-in-lower-risk-myelodysplastic-syndromes-lr-mds-patients/

ASTX727-03: Phase 1 Study Evaluating Oral Decitabine ... The Phase 1 part of this study explores the optimal dosing schedule of LD oral decitabine/cedazuridine in patients with LR-MDS.

6. clinical-lymphoma-myeloma-leukemia.com clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(23)01206-5/abstract

MDS-641 Randomized Phase 1-2 Study to Assess Safety ... MDS-641 Randomized Phase 1-2 Study to Assess Safety and Efficacy of Low-Dose (LD) Oral Decitabine/Cedazuridine (ASTX727) in Lower-Risk Myelodysplastic Syndromes ...