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

Myelodysplastic Syndromes Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05835011
• Other study ID #: ASTX727-10
• Secondary ID: 2022-501548-14-0
• Status: Terminated
• Phase: Phase 2
• Start date: July 14, 2023
• Est. completion date: August 21, 2023

Study information

• Verified date: May 2024
• Source: Astex Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 100
• Est. completion date: August 21, 2023
• Est. primary completion date: August 21, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. 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.

2. Projected life expectancy of at least 3 months.

3. Overall Revised International Prognostic Scoring System for myelodysplastic syndromes (IPSS-R) score =3.5 MDS (immediate risk or higher).

4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of =2.

5. Hematopoietic stem cell transplant (HSCT) eligible without any pre-arranged HSCT on Cycle 1 Day 1, or HSCT ineligible.

6. 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.

Exclusion Criteria:

• Medical Conditions:

1. 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:

1. 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.

2. 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.

2. 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.

3. Known inherited or acquired bleeding disorders that require medication or medical intervention.

4. 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:

5. Immediate eligibility for an allogeneic SCT, as determined by the investigator, with an available donor.

6. Prior therapy for MDS with chemotherapy, allogenic SCT, or =1 full cycle of treatment with any HMA.

7. 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.

8. Prior anti-cluster of differentiation 47 (CD47) treatment.

9. Previous SCT within 6 months before first dose administration, active graft-versus-host disease, or requiring transplant-related immunosuppression.

-Other Exclusions:

10. Known or suspected hypersensitivity to decitabine, cedazuridine, magrolimab, or any of their excipients.

11. 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.

12. Clinical suspicion of active central nervous system (CNS) involvement by MDS.

13. History of psychiatric illness or substance abuse likely to interfere with the ability to comply with protocol requirements or give informed consent.

14. Pregnant or actively breastfeeding.

Related Conditions & MeSH terms

• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• Decitabine/Cedazuridine
Oral FDC tablets administration
• Magrolimab
IV administration

Locations

Country	Name	City	State
United States	Masonic Cancer Center, University of Minnesota	Minneapolis	Minnesota
United States	Yale University	New Haven	Connecticut
United States	BRCR Medical Center	Plantation	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Astex Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events (AEs) Graded According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0		Up to approximately 44 months
Primary	Number of Participants With Dose-Limiting Toxicities (DLTs)	DLTs are defined as any of the following toxicities at least possible 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 toxicity that result in treatment delay of >2 weeks after Cycle 1 (28 days) is complete due to drug-related toxicity.	Cycles 1 and 2 (Cycle=28 days)
Primary	Complete Response (CR) Rate		Up to approximately 44 months
Secondary	Area Under the Plasma Concentration-Time Curve (AUC) of Oral Decitabine/Cedazuridine and Magrolimab		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 (approximately 44 months)
Secondary	Overall Response Rate (ORR)	ORR is defined as percentage of participants with CR, partial response (PR), marrow complete response (mCR), and hematologic improvement (HI).	Up to approximately 44 months
Secondary	Rate of Hematologic Improvement (HI)	HI will include HI with Erythroid (HI-E), HI with Neutrophil (HI-N), or HI with Platelet (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.	Up to approximately 44 months
Secondary	Duration of Progression Free Survival (PFS)		Up to approximately 44 months
Secondary	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.	Up to approximately 44 months
Secondary	Percentage of Participants With Minimal Residual Disease (MRD)-Negative Status		Day 1 of each 28-day Cycle starting from Cycle 3 up to end of study (approximately 44 months)
Secondary	Duration of Response (DOR)		Up to approximately 44 months
Secondary	Overall Survival (OS)		Up to approximately 44 months
Secondary	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.	At screening
Secondary	Number of Participants With p53 Mutation		At screening