Low Dose ASTX727 for Myelodysplastic Syndrome

Recruiting at 42 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

160 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug ASTX727 LD for treating myelodysplastic syndrome?

The research on low-dose melphalan, a component of ASTX727, shows that it can lead to complete remission in some patients with high-risk myelodysplastic syndromes, suggesting potential effectiveness. Additionally, DNA methyltransferase inhibitors, similar to components in ASTX727, have shown positive responses in 20% to 30% of higher-risk MDS patients. ^{1 2 3 4 5}

What is the purpose of this trial?

Multicenter, open-label study of various ASTX727 LD doses and schedules to assess safety, pharmacodynamics, pharmacokinetics, and hematologic response in subjects with International Prognostic Scoring System (IPSS) risk category of low-risk or Intermediate-1 MDS. This study will be conducted in two phases. In phase 1 subjects will be randomized into 3 cohorts in a 28-day cycles. Phase 2, 80 new subjects will be randomized in a 1:1 ratio into 2 doses/schedules.

Research Team

Yuri Sano, MD, PhD

Principal Investigator

Astex Pharmaceuticals, Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Low-dose melphalan for treatment of high-risk myelodysplastic syndromes. [2013]

2. United States pubmed.ncbi.nlm.nih.gov

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

3. England pubmed.ncbi.nlm.nih.gov

Therapeutic strategies in low and high-risk MDS: What does the future have to offer? [2021]

4. United States pubmed.ncbi.nlm.nih.gov

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

5. United States pubmed.ncbi.nlm.nih.gov

Phase II multicenter study of arsenic trioxide in patients with myelodysplastic syndromes. [2018]