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Myelodysplastic SyndromesPhase 2NCT05835011

A Study of Oral Decitabine/Cedazuridine in Combination With Magrolimab in Participants With Intermediate- to Very High-Risk Myelodysplastic Syndromes (MDS)

A Phase 2 study testing Decitabine/Cedazuridine and Magrolimab in people with Myelodysplastic Syndromes, run by Astex Pharmaceuticals, Inc. at 3 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The primary purpose of the study is to evaluate the preliminary safety and efficacy of oral decitabine/cedazuridine in combination with magrolimab. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Myelodysplastic Syndromes
What is being tested?
Decitabine/Cedazuridine and Magrolimab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
3 sitesUnited States
Study dates
27 Jun 2023to 21 Aug 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histological confirmation of previously untreated MDS (i.e., no hypomethylating agent [HMA], chemotherapy, or allogenic stem cell transplant [SCT] per World Health Organization 2016 classification with <20% bone marrow (BM) blasts per marrow biopsy/aspirate at screening.
  • Projected life expectancy of at least 3 months.
  • Overall Revised International Prognostic Scoring System for myelodysplastic syndromes (IPSS-R) score ≥3.5 MDS (immediate risk or higher).
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤2.
  • Hematopoietic stem cell transplant (HSCT) eligible without any pre-arranged HSCT on Cycle 1 Day 1, or HSCT ineligible.
  • Blood type and screen (any of the 4 blood groups A, B, AB, and O [ABO]/rhesus factor [Rh]) along with extended red blood cell phenotyping or genotyping completed prior to study drug treatment.
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  • Hemoglobin ≥9 grams per deciliter (g/dL) on the first day of drug administration, transfusions allowed.
  • Willing to undergo blood transfusions as per parameters of protocol and clinically necessary.
  • White blood cell count ≤20×103/microliters (μL) prior to first dose and throughout study. Hydroxyurea could have been used to achieve this goal prior to and during the first 56 days of magrolimab administration.

Who cannot join

  • Medical Conditions:
  • Known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive), or hepatitis C (e.g., hepatitis C virus ribonucleic acid [HCV RNA] is detected), or chronic hepatitis B or C infection or human immunodeficiency virus (HIV) infection in medical history, with the following exceptions:
  • Those with a history of hepatitis with a negative polymerase chain reaction (either qualitative or quantitative) OR have documentation of stable disease with aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase <2.0×upper limit of normal (ULN) may be eligible for this study.
  • Participants with history of HIV who have an undetectable viral load for the prior 3 months, and who agree to maintain antiviral therapy, may be eligible for the study.
  • Significant medical diseases or conditions, as assessed by the investigators and sponsor, that would substantially increase the risk benefit ratio of participating in the study. This includes, but is not limited to, acute myocardial infarction within the last 6 months, unstable angina, uncontrolled diabetes mellitus, significant active infections, and congestive heart failure New York Heart Association Class III-IV.
  • Known inherited or acquired bleeding disorders that require medication or medical intervention.
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  • Second malignancy, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, or other malignancies for which participants are not on active anticancer therapies and have had no evidence of active malignancy for at least ≥1 year.
  • -Prior/Concomitant Therapy:
  • Immediate eligibility for an allogeneic SCT, as determined by the investigator, with an available donor.
  • Prior therapy for MDS with chemotherapy, allogenic SCT, or ≥1 full cycle of treatment with any HMA.
  • History of therapy-related MDS, MDS evolving from a pre-existing myeloproliferative neoplasm (MPN), MDS/MPN including chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia, juvenile myelomonocytic leukemia, and unclassifiable MDS/MPN.
  • Prior anti-cluster of differentiation 47 (CD47) treatment.
  • Previous SCT within 6 months before first dose administration, active graft-versus-host disease, or requiring transplant-related immunosuppression.
  • -Other Exclusions:
  • Known or suspected hypersensitivity to decitabine, cedazuridine, magrolimab, or any of their excipients.
  • Known significant mental illness or other condition such as active alcohol or other substance abuse or addiction that, in the opinion of the investigator, predisposes the participant to high-risk of noncompliance with the protocol.
  • Clinical suspicion of active central nervous system (CNS) involvement by MDS.
  • History of psychiatric illness or substance abuse likely to interfere with the ability to comply with protocol requirements or give informed consent.
  • Pregnant or actively breastfeeding.

Trial locations and contacts

3 sites in 1 country.

United States3 sites
  • Masonic Cancer Center, University of Minnesota

    Minneapolis, Minnesota, 55455

  • Yale University

    New Haven, Connecticut, 06520

  • BRCR Medical Center

    Plantation, Florida, 33322

Other trials in United States

About this study

Official title: A Phase 2 Study of Oral Decitabine/Cedazuridine in Combination With Magrolimab for Previously Untreated Subjects With Intermediate- to Very High-Risk Myelodysplastic Syndromes (MDS)

The primary purpose of the study is to evaluate the preliminary safety and efficacy of oral decitabine/cedazuridine in combination with magrolimab.

Being tested
Decitabine/Cedazuridine, Magrolimab
Medical subject headings
Myelodysplastic Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Decitabine/CedazuridineDrug

    Also called ASTX727, INQOVI

    Oral FDC tablets administration

  • MagrolimabDrug

    Also called Hu5F9-G4

    IV administration

Study groups in NCT05835011
Study groupRoleWhat they receive
Oral Decitabine/Cedazuridine + MagrolimabExperimentalParticipants will receive 35 milligrams (mg) decitabine/100 mg cedazuridine as a fixed dose combination (FDC) tablet, orally, once daily (QD) on Days 1-5 of each 28-day cycle in combination with magrolimab, intravenous (IV) infusion of 1 milligrams per kilogram (mg/kg) on Days 1 and 4, 15 mg/kg on Day 8, 30 mg/kg on Days 11, 15, 22, 29, 36, 43, and 50, followed by a maintenance dose of 30 mg/kg on Day 57 and every 14 days thereafter until toxicity, progressive disease, withdrawal, death or end of study (approximately 44 months).
Receives: Drug: Decitabine/Cedazuridine; Drug: Magrolimab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Adverse Events (AEs) Graded According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0

    An AE is any untoward medical occurrence in a subject or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention.

    Measured: From signing of informed consent to 30 days after last dose of study drug (Up to 8 weeks)

  2. Number of Participants With Dose-Limiting Toxicities (DLTs)

    DLTs are defined as any of the following toxicities at least possibly related to the treatment regimen: drug-related Grade ≥3 non-hematologic event; grade 4 neutropenia and thrombocytopenia that was not present prior to dosing, that last 28 days or longer and is not related to underlying disease; or any drug-related toxicity that result in treatment delay of >2 weeks after Cycle 1 (28 days) is complete.

    Measured: From signing of informed consent to 30 days after last dose of study drug (Up to 8 weeks)

  3. Complete Response (CR) Rate

    CR defined as per International Working Group (IWG) criteria 2006: Bone marrow (BM) ≤5% myeloblasts with normal maturation of all cell lines; Persistent dysplasia; Peripheral blood; Hemoglobin (Hgb) ≥11 g/dL; Platelets ≥100×109/L; Neutrophils ≥1.0×109/Lb; Blasts 0%. Per the response criteria the response must last ≥4 weeks.

    Measured: Up to 44 months

Secondary outcomes (10)
  1. Area Under the Plasma Concentration-Time Curve (AUC) of Oral Decitabine/Cedazuridine and Magrolimab

    Measured: Decitabine/Cedazuridine: Multiple timepoints pre-dose and post dose up to Day 5 of Cycle 1 and Day 4 of Cycle 2 (Cycle=28 days); Magrolimab: Multiple timepoints pre-dose and post dose up to end of treatment (up to 44 months)

  2. Overall Response Rate (ORR)

    ORR is defined as percentage of participants with CR, partial response (PR), marrow complete response (mCR), and hematologic improvement (HI). CR: Bone marrow (BM) ≤5% myeloblasts with normal maturation of all cell lines; Persistent dysplasia; Peripheral blood; Hemoglobin (Hgb) ≥11 g/dL; Platelets ≥100×109/L; Neutrophils ≥1.0×109/Lb; Blasts 0%. PR: all CR criteria if abnormal before treatment except: BM blasts decreased by ≥50% over pretreatment but still >5%; cellularity and morphology not relevant. mCR: BM ≤5% myeloblasts and decrease by ≥50% over pretreatment; peripheral blood- if HI responses, they are noted in addition to marrow CR. HI include HI with Erythroid (HI-E), HI with Neutrophil (HI-N), or HI with Platelet (HI-P). Per the response criteria the response must last ≥4 weeks for CR, PR and mCR. For HI, the response must last ≥8 weeks.

    Measured: Up to 44 months

  3. Rate of Hematologic Improvement (HI)

    HI include HI-E, HI-N, or HI-P based on the 2006 International Working Group Criteria (IWG 2006). HI-E: Hemoglobin (Hgb) increase ≥1.5g/dL, Relevant reduction of red blood cell (RBC) units transfusions by absolute ≥4 RBC transfusions/8 week compared with pretreatment transfusion number previous 8 week. Only RBC transfusions given for Hgb ≤9.0 g/dL. HI-P: Absolute increase ≥30x10^9/L starting >20x10^9/L platelets (PLTs); Increase from <20x10^9/L to >20x10^9/L and by≥100%. HI-N: ≥100% increase, absolute increase>0.5x10^9/L. Per the response criteria the response must last ≥8 weeks.

    Measured: Up to 44 months

  4. Duration of Progression Free Survival (PFS)

    PFS is defined as time from the date of randomization to the date of disease progression. Disease progression is: For participants with less than 5% blasts: ≥50 increase in blasts to >5% blasts; 5%-10% blasts: ≥50% increase in blasts to >10% blasts; 10%-20% blasts: ≥50% increase in blasts to >20% blasts; 20%-30% blasts: ≥50% increase in blasts to >30% blasts and any of the following: at least 50% decrement from maximum remission/response in granulocytes or platelets; Reduction in Hgb by ≥2 g/dL; transfusion dependence. Per the response criteria the response must last ≥4 weeks.

    Measured: Up to 44 months

  5. Leukemia-free Survival (LFS)

    LFS is defined as the number of days from date of randomization to date when bone marrow or peripheral blood blasts reach ≥20%, or death.

    Measured: Up to 44 months

  6. Percentage of Participants With Minimal Residual Disease (MRD)-Negative Status

    Measured: Day 1 of each 28-day Cycle starting from Cycle 3 up to end of study (up to 44 months)

  7. Duration of Response (DOR)

    DOR is defined as the time from the date that measurement criteria are first met for CR or PR until the first subsequent date that progressive disease or death is documented.

    Measured: Up to 44 months

  8. Overall Survival (OS)

    OS is defined as time from the date of randomization to the date of death from any cause.

    Measured: Up to 44 months

  9. Number of Participants With International Prognostic Scoring System for Myelodysplastic Syndromes (IPSS-M) Score

    The IPSS-M is an algorithm that uses clinical features of participants with MDS and assigns a prognostic score (0=good and increasing in risk by half-grades with the top score outlined below) for three prognostic variables: Marrow blasts (score 0-2.0); Karyotype (score 0-1.0); Cytopenias: neutrophil, platelets, and Hg counts (score 0-0.5). The three individual scores are summed resulting in a full range of 0- 3.5 and placed into risk categories: 0 = low risk; 0.5-1.0 = intermediate-1 risk; 1.5-2.0 = intermediate-2 risk; and >=2.5 = high risk. Higher scores indicate worst outcome.

    Measured: Up to Day 42

  10. Number of Participants With p53 Mutation

    Measured: Up to Day 42

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Apr 2023
  2. Study start27 Jun 2023
  3. Primary completion21 Aug 2023
  4. Study completion21 Aug 2023

Why it stopped: Termination due to discontinuation of magrolimab development in MDS.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05835011
Sponsor's protocol ID
ASTX727-10
Other IDs
2022-501548-14-00
Status last verified
Sep 2024
First submitted
18 Apr 2023
Last updated
2 Oct 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Decitabine/Cedazuridine and Magrolimab in people with Myelodysplastic Syndromes, run by Astex Pharmaceuticals, Inc. at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 2 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Adverse Events (AEs) Graded According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0 (time frame: From signing of informed consent to 30 days after last dose of study drug (Up to 8 weeks)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2024.

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