Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2022-501548-14-00 | Other Identifier | EU CTIS Number |
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Termination due to discontinuation of magrolimab development in MDS.
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The primary purpose of the study is to evaluate the preliminary safety and efficacy of oral decitabine/cedazuridine in combination with magrolimab.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Oral Decitabine/Cedazuridine + Magrolimab | Experimental | Participants 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). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Decitabine/Cedazuridine | Drug | Oral FDC tablets administration |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | 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. | Up to 44 months |
| Measure | Description | Time Frame |
|---|---|---|
| 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 (up to 44 months) | |
| Overall Response Rate (ORR) |
Not provided
Inclusion Criteria:
Exclusion Criteria:
- 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:
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.
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.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Yale University | New Haven | Connecticut | 06520 | United States | ||
| BRCR Medical Center |
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Out of 2 enrolled participants, only 1 received treatment.
2 participants were enrolled at 2 sites in the United States.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Oral Decitabine/Cedazuridine + Magrolimab | Participants were to 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 19, 2022 |
Not provided
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| Magrolimab | Drug | IV administration |
|
|
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. |
| 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. | 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. | 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. | Up to 44 months |
| 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 (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. | 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. | 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. | Up to Day 42 |
| Number of Participants With p53 Mutation | Up to Day 42 |
| Plantation |
| Florida |
| 33322 |
| United States |
| Masonic Cancer Center, University of Minnesota | Minneapolis | Minnesota | 55455 | United States |
| COMPLETED |
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| NOT COMPLETED |
|
|
The study was terminated by the Sponsor. Based on the low enrollment number (n=2), no data, except region of enrollment, is reported here to protect and maintain participant privacy/confidentiality.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Oral Decitabine/Cedazuridine + Magrolimab | Participants were to receive 35 mg decitabine/100 mg cedazuridine as a FDC tablet, orally, QD on Days 1-5 of each 28-day cycle in combination with magrolimab, IV infusion of 1 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | The study was terminated by the Sponsor. Based on the low enrollment number (n=2), no data is reported here to protect and maintain participant privacy/confidentiality. | Mean | Standard Deviation | years |
| |||||||||||||||||||||
| Sex: Female, Male | The study was terminated by the Sponsor. Based on the low enrollment number (n=2), no data is reported here to protect and maintain participant privacy/confidentiality. | Count of Participants | Participants |
| ||||||||||||||||||||||
| Ethnicity (NIH/OMB) | The study was terminated by the Sponsor. Based on the low enrollment number (n=2), no data is reported here to protect and maintain participant privacy/confidentiality. | Count of Participants | Participants |
| ||||||||||||||||||||||
| Race (NIH/OMB) | The study was terminated by the Sponsor. Based on the low enrollment number (n=1), no data is reported here to protect and maintain participant privacy/confidentiality. | Count of Participants | Participants |
| ||||||||||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | 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. | The safety population included the participant who received at least one dose of study treatment. | Posted | Count of Participants | Participants | From signing of informed consent to 30 days after last dose of study drug (Up to 8 weeks) |
|
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| ||||||||||||||||||||||||||
| Primary | 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. | The safety population included participants who received at least one dose of study treatment. | Posted | Count of Participants | Participants | From signing of informed consent to 30 days after last dose of study drug (Up to 8 weeks) |
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| Primary | 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. | As pre-specified in the protocol, analysis of the CR rate was to be conducted 8 months after the enrollment of approximately 100 participants in the study. As only 1 participant received study drug, hence no data was collected for this outcome measure. | Posted | Up to 44 months |
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| Secondary | Area Under the Plasma Concentration-Time Curve (AUC) of Oral Decitabine/Cedazuridine and Magrolimab | Data for this outcome measure was not collected and analyzed as planned as the study was terminated due to discontinuation of magrolimab development in MDS. | Posted | 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) |
|
| ||||||||||||||||||||||||||||||
| 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). 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. | As only 1 participant received study drug, data for this outcome measure was not collected and analyzed as planned as the study was terminated due to discontinuation of magrolimab development in MDS. | Posted | Up to 44 months |
| ||||||||||||||||||||||||||||||
| Secondary | 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. | As only 1 participant received study drug, data for this outcome measure was not collected and analyzed as planned as the study was terminated due to discontinuation of magrolimab development in MDS. | Posted | Up to 44 months |
|
| |||||||||||||||||||||||||||||
| Secondary | 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. | As only 1 participant received study drug, data for this outcome measure was not collected and analyzed as planned as the study was terminated due to discontinuation of magrolimab development in MDS. | Posted | Up to 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. | As only 1 participant received study drug, data for this outcome measure was not collected and analyzed as planned as the study was terminated due to discontinuation of magrolimab development in MDS. | Posted | Up to 44 months |
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| Secondary | Percentage of Participants With Minimal Residual Disease (MRD)-Negative Status | Before Cycle 3 was initiated for 1 participant who received study drug, the study was prematurely terminated due to discontinuation of magrolimab development in MDS. Hence, no data was collected for this outcome | Posted | Day 1 of each 28-day Cycle starting from Cycle 3 up to end of study (up to 44 months) |
|
| ||||||||||||||||||||||||||||||
| Secondary | 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. | As only 1 participant received study drug, data for this outcome measure was not collected and analyzed as planned as the study was terminated due to discontinuation of magrolimab development in MDS. | Posted | Up to 44 months |
|
| |||||||||||||||||||||||||||||
| Secondary | Overall Survival (OS) | OS is defined as time from the date of randomization to the date of death from any cause. | As only 1 participant received study drug, data for this outcome measure was not collected and analyzed as planned as the study was terminated due to discontinuation of magrolimab development in MDS. | Posted | Up to 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. | As only 1 participant received study drug, data for this outcome measure was not collected and analyzed as planned as the study was terminated due to discontinuation of magrolimab development in MDS. | Posted | Up to Day 42 |
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| Secondary | Number of Participants With p53 Mutation | As only 1 participant received study drug, data for this outcome measure was not collected and analyzed as planned as the study was terminated due to discontinuation of magrolimab development in MDS. | Posted | Up to Day 42 |
|
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From signing of informed consent to 30 days after last dose of study drug (Up to 8 weeks)
The safety population included the participant who received at least one dose of study treatment.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Oral Decitabine/Cedazuridine + Magrolimab | Participants were to receive 35 mg decitabine/100 mg cedazuridine as a FDC tablet, orally, QD on Days 1-5 of each 28-day cycle in combination with magrolimab, IV infusion of 1 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. | 0 | 1 | 0 | 1 | 1 | 1 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Platelet count decreased | Investigations | Systematic Assessment |
| ||
| Blood bilirubin increased | Investigations | Systematic Assessment |
| ||
| Intermittent dizziness | Nervous system disorders | Systematic Assessment |
| ||
| Intermittent anaemia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Intermittent platelet count decreased | Investigations | Systematic Assessment |
| ||
| Neutrophil count decreased | Investigations | Systematic Assessment |
| ||
| White blood cell count decreased | Investigations | Systematic Assessment |
|
The study was terminated prematurely due to discontinuation of magrolimab development in MDS.
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Taiho Central | Taiho Oncology, Inc. | 844-878-2446 | medicalinformation@taihooncology.com |
| Sep 6, 2024 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D009190 | Myelodysplastic Syndromes |
| ID | Term |
|---|---|
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000723076 | decitabine and cedazuridine drug combination |
| C000629291 | magrolimab |
Not provided
Not provided
Not provided
| More than one race |
| Unknown or Not Reported |
|
| Units | Counts |
|---|---|
| Participants |
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| Participants |
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