The primary purpose of the study is to evaluate the preliminary safety and efficacy of oral decitabine/cedazuridine in combination with magrolimab.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
2
Oral FDC tablets administration
IV administration
Yale University
New Haven, Connecticut, United States
BRCR Medical Center
Plantation, Florida, United States
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States
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.
Time frame: From signing of informed consent to 30 days after last dose of study drug (Up to 8 weeks)
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.
Time frame: From signing of informed consent to 30 days after last dose of study drug (Up to 8 weeks)
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.
Time frame: Up to 44 months
Area Under the Plasma Concentration-Time Curve (AUC) of Oral Decitabine/Cedazuridine and Magrolimab
Time frame: 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)
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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.
Time frame: Up to 44 months
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.
Time frame: Up to 44 months
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.
Time frame: Up to 44 months
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.
Time frame: Up to 44 months
Percentage of Participants With Minimal Residual Disease (MRD)-Negative Status
Time frame: Day 1 of each 28-day Cycle starting from Cycle 3 up to end of study (up to 44 months)
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.
Time frame: Up to 44 months
Overall Survival (OS)
OS is defined as time from the date of randomization to the date of death from any cause.
Time frame: Up to 44 months
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.
Time frame: Up to Day 42
Number of Participants With p53 Mutation
Time frame: Up to Day 42