Myelodysplastic Syndrome ( a group of bone marrow disorders in which the production of blood cells is seriously disturbed)
Conditions
Interventions
Magrolimab + azacitidine, or azacitidine + placebo as follows:
Magrolimab will be dosed intravenously (IV).
• Priming doses of magrolimab: 1 mg/kg on Days 1 and 4
15 mg/kg on Day 8
30
mg/kg on Days 11 and 15
and then 30 mg/kg weekly for a total of 5 doses (on
Days 22, 29, 36, 43, and 50).
• Maintenance doses of magrolimab: 30 mg/kg on Day 57, and 30 mg/kg every 2
weeks thereafter.
Placebo
• Saline plac
Sponsors
Gilead Sciences
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Participants with MDS defined according to World Health Organization classification, with an IPSS-R prognostic risk category of intermediate, high, or very high risk. Note: participants who require AML-like therapy are not eligible. Prior and concurrent therapy with hydroxyurea, oral etoposide, erythroid, and/or myeloid growth factors is allowed. 2. White blood cell (WBC) count = 18 years. 6. Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 2. 7. Willing to undergo blood transfusions as deemed clinically necessary. 8. Pretreatment blood cross-match including ABO (any of the 4 blood groups A, B, AB, and O comprising the ABO system)/Rh (Rhesus factor), DAT (direct antiglobulin test), and phenotyping or genotyping completed. 9. Biochemical indices within the ranges shown below: a. Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase = 40 mL/min/1.73 m2 10. All participants must have a documented hemoglobin >=9.0 g/dL within 24 hours prior to the first two doses of magrolimab/placebo infusion. Participants who do not meet these criteria must be transfused and have their hemoglobin rechecked to meet the minimum haemoglobin threshold prior to administering each of the first 2 doses of magrolimab/placebo. Transfusions are allowed in order to meet hemoglobin eligibility. 11. Female participants of childbearing potential must not be nursing or planning to be pregnant and must have a negative urine or serum pregnancy test within 30 days before randomization and within 72 hours before the first administration of study treatment. 12. Male participants and female participants of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified methods of contraception as described in protocol Appendix H. 13. Willing to consent to mandatory pretreatment and on-treatment bone marrow biopsies (trephines), unless not feasible as determined by the Investigator and discussed with the Sponsor.
Exclusion criteria
Exclusion criteria: 1. Prior treatment with CD47 or SIRPa-targeting agents. 2. Prior therapy for the treatment of MDS with an IPSS-R prognostic risk category of intermediate, high or very high risk (excluding hydroxyurea or oral etoposide), prior treatment with hypomethylating agents and/or low dose cytarabine. NOTE: Localized noncentral nervous system (CNS) radiotherapy, erythroid and/or myeloid growth factors, previous hormonal therapy with luteinizing hormone-releasing hormone (LHRH) agonists for prostate cancer, and treatment with bisphosphonates and receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors are not criteria for exclusion. Prior lenalidomide is also not exclusionary. 3.Immediately eligible for an allogeneic SCT, as determined by the Investigator, with an available donor. 4. Contraindications to azacitidine, including advanced malignant hepatic tumors or known hypersensitivity to azacitidine or mannitol. 5. Known inherited or acquired bleeding disorders. 6. Previous SCT within 6 months prior to randomization, active graft-versus-host disease, or requiring transplant-related immunosuppression. 7. Clinical suspicion of active CNS involvement by MDS. 8. 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. 9. 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. 10. History of psychiatric illness or substance abuse likely to interfere with the ability to comply with protocol requirements or give informed consent. 11. Pregnancy or active breastfeeding. 12. Known active or chronic hepatitis B or C infection or HIV infection in medical history. 13. Active hepatitis B virus (HBV) and/or active hepatitis C virus (HCV), and/or HIV following testing at screening: a) Participants who test positive for hepatitis B surface antigen (HBsAg). Participants who test positive for hepatitis B core antibody (anti-HBc) will require HBV DNA by quantitative polymerase chain reaction (PCR) for confirmation of active disease. b) Participants who test positive for HCV antibody. These participants will require HCV RNA by quantitative PCR for confirmation of active disease. c) Participants who test positive for HIV antibody. d) Participants not currently on antiviral therapy and who have an undetectable viral load in the prior 3 months may be eligible for the study.
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| See protocol section 3. Objectives and endpoints | — |
Primary
| Measure | Time frame |
|---|---|
| Endpoints: * CR rate as assessed by Investigators: The CR rate is the proportion of participants who reach morphologic CR (morphological blast of | — |
Countries
Netherlands
Outcome results
None listed