Clinical trial NCT05835011: A Study of Oral Decitabine/Cedazuridine in Combination With Magrolimab in Participants With Intermediate- to Very High-Risk Myelodysplastic Syndromes (MDS)
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Myelodysplastic Syndromes
Lead sponsor: Astex Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2023-04-28
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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.
7. Hemoglobin ≥9 grams per deciliter (g/dL) on the first day of drug administration, transfusions allowed.
8. Willing to undergo blood transfusions as per parameters of protocol and clinically necessary.
9. 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.

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.

Primary outcomes:
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
timeFrame: From signing of informed consent to 30 days after last dose of study drug (Up to 8 weeks)
measure: Number of Participants With Dose-Limiting Toxicities (DLTs)
timeFrame: From signing of informed consent to 30 days after last dose of study drug (Up to 8 weeks)
measure: Complete Response (CR) Rate
timeFrame: Up to 44 months
Secondary outcomes:
measure: Area Under the Plasma Concentration-Time Curve (AUC) of Oral Decitabine/Cedazuridine and Magrolimab
timeFrame: 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)
measure: Overall Response Rate (ORR)
timeFrame: Up to 44 months
measure: Rate of Hematologic Improvement (HI)
timeFrame: Up to 44 months
measure: Duration of Progression Free Survival (PFS)
timeFrame: Up to 44 months
measure: Leukemia-free Survival (LFS)
timeFrame: Up to 44 months
measure: Percentage of Participants With Minimal Residual Disease (MRD)-Negative Status
timeFrame: Day 1 of each 28-day Cycle starting from Cycle 3 up to end of study (up to 44 months)
measure: Duration of Response (DOR)
timeFrame: Up to 44 months
measure: Overall Survival (OS)
timeFrame: Up to 44 months
measure: Number of Participants With International Prognostic Scoring System for Myelodysplastic Syndromes (IPSS-M) Score
timeFrame: Up to Day 42
measure: Number of Participants With p53 Mutation
timeFrame: Up to Day 42
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Plantation
country: United States
facility: BRCR Medical Center
state: Florida
city: Minneapolis
country: United States
facility: Masonic Cancer Center, University of Minnesota
state: Minnesota
Study officials:
References: