Magrolimab Monotherapy or Magrolimab in Combination With Azacitidine in Participants With Hematological Malignancies

Phase 1

Terminated

Conditions: Hematological Malignancies

Interventions: Drug: Magrolimab
Drug: Azacitidine

Registration Number: NCT03248479

Lead Sponsor: Gilead Sciences

Brief Summary: The primary objectives of this study are:

* To confirm the safety and tolerability of magrolimab monotherapy in a relapsed/refractory (R/R) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) population, and of magrolimab in combination with azacitidine in previously untreated participants with AML or MDS and participants with R/R AML and MDS

* To evaluate the efficacy of magrolimab monotherapy in R/R AML/MDS, and of magrolimab in combination with azacitidine in previously untreated participants with AML/MDS, or R/R AML/MDS as measured by complete remission (CR) rate for participants with AML and higher-risk MDS, and duration of complete response for participants with AML and higher-risk MDS, and duration of CR for participants with AML and higher-risk MDS

* To evaluate the safety, tolerability, and efficacy of magrolimab monotherapy or combination with azacitidine in low-risk MDS participants as measured by red blood cell (RBC) transfusion independence rate

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 258

Inclusion Criteria

Meets the criteria below for the appropriate cohort:
- Relapsed/Refractory Cohorts: Pathologically confirmed relapsed or refractory (primary refractory and/or relapsed refractory) acute myeloid leukemia (AML) or confirmed intermediate, high, or very high risk myelodysplastic syndromes (MDS) that is relapsed, refractory or intolerant to conventional therapy.
- Treatment-naive/Unfit Cohorts: Previously untreated individuals with histological confirmation of AML who are ineligible for treatment with a standard cytarabine and anthracycline induction regimen; or previously untreated individuals with intermediate, high, or very high risk MDS. Prior and concurrent therapy with hydroxyurea, oral etoposide, erythroid and/or myeloid growth factors is allowed.
- Rollover Cohort: Individuals on active magrolimab therapy on the Phase 1 AML (SCI-CD47-002; NCT02678338) trial who are deriving clinical benefit by Investigator assessment.
- RBC transfusion dependent low risk MDS cohort: Transfusion-dependent MDS individuals who are very low or low risk by Revised International Prognostic Scoring System (IPSS-R) with previous treatment with an erythroid stimulating agent or lenalidomide.
White blood cell (WBC) count ≤ 20 x 10^3/mcL
Adequate performance status and hematological, liver, and kidney function.

Key

Exclusion Criteria

Prior treatment with cluster of differentiation 47 (CD47) or signal regulatory protein alpha (SIRPα) targeting agents (with exception of magrolimab for individuals in the Rollover cohort).
Treatment-naive/Unfit Cohorts Only: Any prior anti-leukemic therapy (excluding hydroxyurea or oral etoposide), prior treatment with hypomethylating agents and/or low dose cytarabine.
Acute promyelocytic leukemia.
Known inherited or acquired bleeding disorders.
Previous allogeneic hematopoietic stem cell transplant within 6 months prior to enrollment, active graft versus host disease (GVHD), or requiring transplant-related immunosuppression.
Clinical suspicion of active central nervous system (CNS) involvement by leukemia.
Known active or chronic hepatitis B or C infection or HIV.
Pregnancy or active breastfeeding.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TN MDS Cohort Higher Risk QW 30 mg/kg	Magrolimab	Participants who are treatment-naive (TN) with higher risk myelodysplastic syndrome (MDS) will receive 1 mg/kg magrolimab on Cycle 1 (Days 1, 4); 15 mg/kg on Cycle 1 Day 8; 30 mg/kg on Cycle 1 Days 11, 15, 22, and then weekly (QW) starting Cycle 2 up to end of the study. Participants will receive azacitidine 75 mg/m\^2 on Days 1 to 7 of each cycle (each cycle was of 28 days). Maximum treatment duration was up to 4 years.
TN MDS Cohort Higher Risk QW 30 mg/kg	Azacitidine	Participants who are treatment-naive (TN) with higher risk myelodysplastic syndrome (MDS) will receive 1 mg/kg magrolimab on Cycle 1 (Days 1, 4); 15 mg/kg on Cycle 1 Day 8; 30 mg/kg on Cycle 1 Days 11, 15, 22, and then weekly (QW) starting Cycle 2 up to end of the study. Participants will receive azacitidine 75 mg/m\^2 on Days 1 to 7 of each cycle (each cycle was of 28 days). Maximum treatment duration was up to 4 years.
TN MDS Cohort Higher Risk Q2W 30 mg/kg	Magrolimab	Participants who are TN with higher risk MDS will receive 1 mg/kg magrolimab on Cycle 1 (Days 1, 4); 15 mg/kg on Cycle 1 Day 8; 30 mg/kg on Cycle 1 Days 11, 15, 22, and then weekly starting Cycle 2 and given every 2 weeks (Q2W) from Cycle 3 up to end of the study. Participants will receive azacitidine 75 mg/m\^2 on Days 1 to 7 of each cycle (each cycle was of 28 days). Maximum treatment duration was up to 4 years.
TN MDS Cohort Higher Risk Q2W 30 mg/kg	Azacitidine	Participants who are TN with higher risk MDS will receive 1 mg/kg magrolimab on Cycle 1 (Days 1, 4); 15 mg/kg on Cycle 1 Day 8; 30 mg/kg on Cycle 1 Days 11, 15, 22, and then weekly starting Cycle 2 and given every 2 weeks (Q2W) from Cycle 3 up to end of the study. Participants will receive azacitidine 75 mg/m\^2 on Days 1 to 7 of each cycle (each cycle was of 28 days). Maximum treatment duration was up to 4 years.
TN/U AML Cohort: Magrolimab + Azacitidine	Magrolimab	Participants who are treatment-naive or unfit (TN/U) with acute myeloid leukemia (AML) will receive 1 mg/kg magrolimab on Cycle 1 (Days 1, 4); 15 mg/kg on Cycle 1 Day 8; 30 mg/kg on Cycle 1 Days 11, 15, 22, and then QW starting Cycle 2 and then given QW and Q2W from Cycle 3 up to end of the study. Participants will receive azacitidine 75 mg/m\^2 on Days 1 to 7 of each cycle (each cycle was of 28 days). Maximum treatment duration was up to 4 years.
TN/U AML Cohort: Magrolimab + Azacitidine	Azacitidine	Participants who are treatment-naive or unfit (TN/U) with acute myeloid leukemia (AML) will receive 1 mg/kg magrolimab on Cycle 1 (Days 1, 4); 15 mg/kg on Cycle 1 Day 8; 30 mg/kg on Cycle 1 Days 11, 15, 22, and then QW starting Cycle 2 and then given QW and Q2W from Cycle 3 up to end of the study. Participants will receive azacitidine 75 mg/m\^2 on Days 1 to 7 of each cycle (each cycle was of 28 days). Maximum treatment duration was up to 4 years.
R/R AML Cohort: Magrolimab + Azacitidine	Magrolimab	Participants with relapsed/refractory (r/r) AML will receive magrolimab 1 mg/kg for Cycle 1 Week 1 (Days 1, 4); 15 mg/kg on Cycle 1 Day 8, 30 mg/kg on Cycle 1 Days 11, 15 and 22 through end of Cycle 2 and then 30 mg/kg QW in Cycle 2 and then 30 mg/kg QW and Q2W starting Cycle 3 and thereafter (each cycle was of 28 days). Participants will receive azacitidine 75 mg/m\^2 on Days 1 to 7 of each cycle (each cycle was of 28 days). Maximum treatment duration was up to 4 years.
R/R AML Cohort: Magrolimab + Azacitidine	Azacitidine	Participants with relapsed/refractory (r/r) AML will receive magrolimab 1 mg/kg for Cycle 1 Week 1 (Days 1, 4); 15 mg/kg on Cycle 1 Day 8, 30 mg/kg on Cycle 1 Days 11, 15 and 22 through end of Cycle 2 and then 30 mg/kg QW in Cycle 2 and then 30 mg/kg QW and Q2W starting Cycle 3 and thereafter (each cycle was of 28 days). Participants will receive azacitidine 75 mg/m\^2 on Days 1 to 7 of each cycle (each cycle was of 28 days). Maximum treatment duration was up to 4 years.
R/R AML Cohort: Magrolimab	Magrolimab	Participants with r/r AML will receive magrolimab 1 mg/kg for Cycle 1 Week 1 (Days 1, Day 4); 15 mg/kg on Cycle 1 Day 8, 30 mg/kg on Cycle 1 Day 11 and Day 15, 30 mg/kg weekly on Cycle 1 Day 22 through end of Cycle 2, and 30 mg/kg Q2W starting Cycle 3 and thereafter (each cycle was of 28 days). Maximum treatment duration was up to 4 years.
Rollover AML Cohort: Magrolimab	Magrolimab	Participants may receive the same dose level and schedule (30 mg/kg) (i.e., twice weekly) of magrolimab monotherapy in each cycle (each cycle was of 28 days) as previously received on the Phase 1 AML study (SCI-CD47-002), or may transition to once-weekly dosing in this study at the discretion of the Investigator in each 28-day cycle and with Sponsor approval. Maximum treatment duration was up to 4 years.
R/R MDS Cohort: Magrolimab + Azacitidine	Magrolimab	Participants with r/r MDS will receive magrolimab 1 mg/kg for Cycle 1 Week 1 (Days 1, 4); 15 mg/kg on Cycle 1 Day 8, 30 mg/kg on Cycle 1 Days 11, 15 and 22 through end of Cycle 2 and then 30 mg/kg QW in Cycle 2 and then 30 mg/kg Q2W starting Cycle 3 and thereafter (each cycle was of 28 days). Participants will receive azacitidine 75 mg/m\^2 on Days 1 to 7 of each cycle (each cycle was of 28 days). Maximum treatment duration was up to 4 years.
R/R MDS Cohort: Magrolimab + Azacitidine	Azacitidine	Participants with r/r MDS will receive magrolimab 1 mg/kg for Cycle 1 Week 1 (Days 1, 4); 15 mg/kg on Cycle 1 Day 8, 30 mg/kg on Cycle 1 Days 11, 15 and 22 through end of Cycle 2 and then 30 mg/kg QW in Cycle 2 and then 30 mg/kg Q2W starting Cycle 3 and thereafter (each cycle was of 28 days). Participants will receive azacitidine 75 mg/m\^2 on Days 1 to 7 of each cycle (each cycle was of 28 days). Maximum treatment duration was up to 4 years.
R/R MDS Cohort: Magrolimab to Magrolimab + Azacitidine	Magrolimab	Participants with r/r MDS will receive magrolimab 1 mg/kg for Cycle 1 Week 1 (Days 1, 4); 15 mg/kg on Cycle 1 Day 8, 30 mg/kg on Cycle 1 Days 11, 15 and 22 through end of Cycle 2 and then 30 mg/kg QW in Cycle 2 and then 30 mg/kg Q2W starting Cycle 3 and thereafter (each cycle was of 28 days). Participants will receive azacitidine 75 mg/m\^2 on Days 1 to 7 of each cycle (each cycle was of 28 days). Maximum treatment duration was up to 4 years. Participants with r/r MDS who do not have an objective response with magrolimab at the first protocol response assessment can have azacitidine added to magrolimab for subsequent cycles.
R/R MDS Cohort: Magrolimab to Magrolimab + Azacitidine	Azacitidine	Participants with r/r MDS will receive magrolimab 1 mg/kg for Cycle 1 Week 1 (Days 1, 4); 15 mg/kg on Cycle 1 Day 8, 30 mg/kg on Cycle 1 Days 11, 15 and 22 through end of Cycle 2 and then 30 mg/kg QW in Cycle 2 and then 30 mg/kg Q2W starting Cycle 3 and thereafter (each cycle was of 28 days). Participants will receive azacitidine 75 mg/m\^2 on Days 1 to 7 of each cycle (each cycle was of 28 days). Maximum treatment duration was up to 4 years. Participants with r/r MDS who do not have an objective response with magrolimab at the first protocol response assessment can have azacitidine added to magrolimab for subsequent cycles.
R/R MDS Cohort: Magrolimab	Magrolimab	Participants with r/r MDS will receive 1 mg/kg magrolimab on Cycle 1 Week 1 (Days 1, 4); 15 mg/kg on Cycle 1 Day 8; 30 mg/kg on Cycle 1 Days 11, 15, 22, through end of Cycle 2 and then 30 mg/kg QW in Cycle 2 and then 30 mg/kg Q2W starting Cycle 3 and thereafter (each cycle was of 28 days). Maximum treatment duration was up to 4 years.
Low Risk MDS Cohort: Magrolimab + Azacitidine	Magrolimab	Participants with low risk MDS will receive 1 mg/kg magrolimab on Cycle 1 Week 1 Day 1; 30 mg/kg on Cycle 1 Days 8, 15 and 22; 60 mg/kg on Day 1 of Cycle 2 and subsequent cycles (each cycle was of 28 days) (each cycle was of 28 days) up to the end of the study. Participants will receive azacitidine 75 mg/m\^2 on Days 1 to 5 of each cycle. For participants who could not tolerate 60 mg/kg dose, the dose of magrolimab was reduced to 45 mg/kg. Maximum treatment duration was up to 4 years.
Low Risk MDS Cohort: Magrolimab + Azacitidine	Azacitidine	Participants with low risk MDS will receive 1 mg/kg magrolimab on Cycle 1 Week 1 Day 1; 30 mg/kg on Cycle 1 Days 8, 15 and 22; 60 mg/kg on Day 1 of Cycle 2 and subsequent cycles (each cycle was of 28 days) (each cycle was of 28 days) up to the end of the study. Participants will receive azacitidine 75 mg/m\^2 on Days 1 to 5 of each cycle. For participants who could not tolerate 60 mg/kg dose, the dose of magrolimab was reduced to 45 mg/kg. Maximum treatment duration was up to 4 years.
Low Risk MDS Cohort: Magrolimab to Magrolimab + Azacitidine	Magrolimab	Participants with low risk MDS will receive 1 mg/kg magrolimab on Cycle 1 Week 1 Day 1; 30 mg/kg on Cycle 1 Days 8, 15 and 22; 60 mg/kg on Day 1 of Cycle 2 and subsequent cycles (each cycle was of 28 days) (each cycle was of 28 days) up to the end of the study. Participants will receive azacitidine 75 mg/m\^2 on Days 1 to 5 of each cycle. For participants who could not tolerate 60 mg/kg dose, the dose of magrolimab was reduced to 45 mg/kg. Maximum treatment duration was up to 4 years. Participants with r/r MDS who do not have an objective response with magrolimab at the first protocol response assessment can have azacitidine added to magrolimab for subsequent cycles.
Low Risk MDS Cohort: Magrolimab to Magrolimab + Azacitidine	Azacitidine	Participants with low risk MDS will receive 1 mg/kg magrolimab on Cycle 1 Week 1 Day 1; 30 mg/kg on Cycle 1 Days 8, 15 and 22; 60 mg/kg on Day 1 of Cycle 2 and subsequent cycles (each cycle was of 28 days) (each cycle was of 28 days) up to the end of the study. Participants will receive azacitidine 75 mg/m\^2 on Days 1 to 5 of each cycle. For participants who could not tolerate 60 mg/kg dose, the dose of magrolimab was reduced to 45 mg/kg. Maximum treatment duration was up to 4 years. Participants with r/r MDS who do not have an objective response with magrolimab at the first protocol response assessment can have azacitidine added to magrolimab for subsequent cycles.
Low Risk MDS Cohort: Magrolimab	Magrolimab	Participants with low risk MDS will receive 1 mg/kg magrolimab on Cycle 1 Week 1 Day 1; 30 mg/kg on Cycle 1 Days 8, 15 and 22; 60 mg/kg on Day 1 of Cycle 2 and subsequent cycles (each cycle was of 28 days) (each cycle was of 28 days) up to the end of the study. Maximum treatment duration was up to 4 years.

Primary Outcome Measures

Name	Time	Method
Complete Remission (CR) Rate For Participants With AML	Up to 5 years	The CR rate is the percentage of participants who achieved CR without minimal residual disease (CRMRD-), and CR as per European Leukemia Net (ELN) AML recommendations. CRMRD- per ELN was defined as neutrophils ≥1.0 × 10\^9/L; platelets ≥100 × 10\^9/L and \<5% bone marrow blasts. If studied pretreatment, CR with negativity for a genetic marker by real-time quantitative polymerase chain reaction (RT-qPCR) or similar modality or CR with negativity by multi-color flow cytometry. CR per ELN criteria is defined as neutrophils ≥1.0 × 10\^9/L; platelets ≥100 × 10\^9/L and \<5% bone marrow blasts. Absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; MRD positive or unknown.
CR Rate for Participants With MDS	Up to 5 years	The CR rate was the percentage of MDS participants who achieved CR per International Working Group (IWG) 2006 criteria. CR per IWG criteria is defined as bone marrow ≤5% myeloblasts with normal maturation of all cell lines. Persistent dysplasia will be noted. Peripheral blood should have: Hemoglobin (Hgb) ≥11 g/dL, platelets ≥100 × 10\^9/L, neutrophils ≥1.0 × 10\^9/L and blasts 0%.
Percentage of Participants With Red Blood Cell (RBC) Transfusion Independence for Participants With Low-Risk MDS	Up to 8 weeks	RBC transfusion independence was defined by the lack of RBC transfusions for at least an 8 week consecutive period at any time after starting therapy.
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)	Up to 4 years	TEAEs were defined as any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug and before the first date of new anti-cancer therapy including stem-cell transplant (SCT) and/or any AEs leading to premature discontinuation of study drug.

Secondary Outcome Measures

Name	Time	Method
Minimal Residual Disease (MRD) Negative Response Rate	Up to 5 years	The MRD-negative response rate was defined as the percentage of participants who reach MRD-negative disease status prior to initiation of other new anti-cancer therapy including SCT and achieve a morphologic CR or marrow CR for MDS participants and achieve CR/CRi/CRh/MLFS for AML participants. MRD-negative disease status will be assessed using a multiparameter flow cytometry-based assay performed by a central laboratory. CR/CRi/MLFS/CRh were defined in outcome measures 2, 9, 10 respectively. Marrow CR was defined in outcome measure 8.
Serum Concentration for Magrolimab in TN/U AML and TN MDS Participants	Predose and/or after 1 hour of infusion (duration 3 hours (± 30 minutes) for 1mg/kg; 2 hours for 15 mg/kg, 30 mg/kg and 60 mg/kg) in Cycles (each cycle of 28 days) 1 to 7, 9, 11, 13, 15, on Days 1, 2, 3, 4, 8, 11, 15, 16, 17, 18, 22, EOT, Safety Follow-up
Percentage of Participants Who Developed Anti-Magrolimab Antibodies	Up to 5 years	As per the pre-specified analysis, this outcome measure was analyzed based on different dosing regimens and timepoints when magrolimab was given alone and in combination with the azacitidine. Therefore, the data is reported for magrolimab as monotherapy and magrolimab plus azacitidine. Also, the arms are based on the frequency of magrolimab administered: QW, Q2W, QW to Q2W, Q4W, BIW and BIW to QW as applicable in different cohorts.
Duration of Complete Remission (DCR) in Participants With AML and MDS	Up to 5 years	For AML participants: The DCR was defined as the time measurement criteria were first met for CR (including morphologic CR, CRMRD-, cytogenetic complete remission (cCR), and molecular complete remission (mCR) until the first date that recurrent disease or death with evidence of no disease recurrence was objectively documented. CR and CRMRD- were defined in outcome measure 2. cCR was defined as complete disappearance of chromosomal abnormality without appearance of new ones. mCR was defined as morphological blast of ≤ 5% and recovery of absolute neutrophil count (ANC), platelets, and hemoglobin from complete blood counts as well as peripheral blast. For MDS participants: The DCR was defined as the time measurement criteria were first met for CR until the first date that recurrent disease or death with evidence of no disease recurrence is objectively documented. Kaplan-Meier (KM) estimates were used in the outcome measure analysis.
Percentage of MDS Participants With Objective Response Rate (ORR) as Defined by IWG 2006 MDS Response Criteria	Up to 5 years	ORR was the percentage of participants who achieved CR, partial remission (PR), marrow CR or hematological improvement (HI) prior to initiation of a new anticancer therapy including SCT per IWG 2006 criteria per investigator's evaluation. CR was defined in outcome measure 2. PR was defined as all CR criteria if abnormal before treatment except the bone marrow blasts decreased by 50% over pretreatment but still \> 5% and cellularity and morphology not relevant. Marrow CR is defined as bone marrow ≤5% myeloblasts and decrease by ≥50% over pretreatment, stable disease with any hematological improvement, peripheral blood: if hematological improvement responses, they were noted in addition to marrow CR. Stable Disease: Failure to achieve at least PR, but no evidence of progression for \> 8 weeks. Percentages were rounded off.
Percentage of AML Participants With Objective Response Rate (ORR)	Up to 5 years	ORR is the percentage of participants who achieve CR, CR with incomplete hematologic (count) recovery (CRi), CR with partial hematologic (count) recovery (CRh), Partial Response (PR), Morphologic Leukemia-Free State (MLFS) prior to initiation of a new anti-cancer therapy including SCT per European Leukemia Net (ELN) AML 2017 recommendations per investigator's evaluation. CR was defined in outcome measure 2. CRi was defined as neutrophils ≥ 1.0 × 10\^9/L or platelets ≥ 100 × 10\^9/L bone marrow blasts \< 5%. Absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; MRD positive or unknown. CRh was defined in outcome measure 10. PR was defined in outcome measure 8. MLFS was defined as bone marrow blasts \< 5%. Absence of blasts with Auer rods; absence of extramedullary disease; no hematologic recovery required; marrow should not merely be "aplastic"; at least 200 cells should be enumerated or cellularity should be at least 10%.
Overall Survival (OS) for Participants With AML or MDS	Up to 5 years	The length of overall survival will be measured from the date of study treatment initiation until the date of death from any cause. KM estimates were used in the outcome measure analysis.
Percentage of Participants With Complete Remission With Partial Hematologic Recovery (CRh) for AML Participants	Up to 5 years	CRh was defined as CR with partial platelet and absolute neutrophil count recovery while on study prior to initiation of any new anti-acute myeloid leukemia (AML) therapy or stem cell transplant (SCT).
Duration of Response for Participants With MDS	Up to 5 years	The DOR was measured from the time measurement criteria were first met for objective response as assessed by IWG MDS criteria until the first date that recurrent disease or death with evidence of no disease recurrence is objectively documented. KM estimates were used in the outcome measure analysis.
Duration of Response (DOR) for Participants With AML	Up to 5 years	The DOR was defined as time measurement criteria were met for complete remission (CR) (including morphologic CR, CRMRD-, cytogenetic complete remission (cCR), and molecular complete remission (mCR), incomplete blood count recovery (CRi), partial hematologic recovery (CRh), partial remission (PR), marrow CR, or morphologic leukemia-free state (MLFS), whichever was first recorded, until the first date that recurrent or progressive disease, or death with evidence of no disease magrolimab progression is objectively documented. CR and CRMRD- were defined in outcome measure 2. cCR and mCR were defined in outcome measure 7. Marrow CR and PR were defined in outcome measure 8. CRi and MLFS were defined in outcome measure 9. CRh was defined in outcome measure 10. KM estimates were used in the outcome measure analysis.
Progression Free Survival (PFS) for Participants With AML or MDS	Up to 5 years	The length of PFS is defined as the time from the date of study treatment initiation until the date of documented disease progression (PD) or death from any cause, whichever occurs first. PD for MDS: \<5% blasts: if blasts increase ≥50% to \>5%; 5%-10% blasts: if blasts increase ≥50% to \>10%; 10%-20% blasts: if blasts increase ≥50% to \>20%; 20%-30% blasts: if blasts increase ≥50% to \>30%. Participants with at least 50% decrement from maximum remission/response in granulocytes / platelets or reduction in Hgb by ≥ 2 g/dL or transfusion dependence. PD for AML was defined as any evidence for an increase in bone marrow blast percentage and/or increase of absolute blast counts in the blood: \> 50% increase in marrow blasts over baseline (a minimum 15% point increase is required in cases with \< 30% blasts at baseline; or persistent marrow blast percentage of \>70% over at least 3 months; without at least a 100% improvement in absolute neutrophil count.
Relapse Free Survival (RFS) for Participants With AML or MDS	Up to 5 years	The length of RFS is defined from the first date of attaining a CR (including morphologic CR, CRMRD-, cCR, and mCR) until the date of AML relapse or death from any cause, whichever occurs first.
Event Free Survival (EFS) for Participants With AML or MDS	Up to 5 years	For AML, EFS was defined as the time from the date of study treatment initiation until the date of documented disease progression, death from any cause, or treatment failure (defined as failure to achieve CR/CRi/CRh by Cycle 5 Day 1), whichever occurred first. CR/CRi/CRh were defined in outcome measures 2, 9 and 10 respectively. For MDS, EFS was defined as the time from the date of study treatment initiation to transformation to AML or death from any cause, whichever occurred first. Participants who were not observed to have one of these events during the study were censored at their last response assessment date with evidence of no transformation to AML. KM estimates were used in the outcome measure analysis.
Change From Baseline in Hemoglobin on Therapy	Baseline and Day 1
12-week RBC Transfusion Independence Rates	Up to 12 Weeks

Trial Locations

Locations (27): The University of Chicago
🇺🇸
Chicago, Illinois, United States
City of Hope National Medical Center
🇺🇸
Duarte, California, United States
University of California Davis Comprehensive Cancer Center
🇺🇸
Sacramento, California, United States
Chao Family Comprehensive Cancer Center - UC Irvine Medical Center
🇺🇸
Orange, California, United States
UCLA Clinical and Translational Research Center (CTRC)
🇺🇸
Los Angeles, California, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Mid America Division, Inc.
🇺🇸
Kansas City, Missouri, United States
Tennesssee Oncology - Centennial Clinic Location
🇺🇸
Nashville, Tennessee, United States
University of California San Diego (UCSD)
🇺🇸
La Jolla, California, United States
Stanford University Medical Center
🇺🇸
Stanford, California, United States
University of Colorado Cancer Center
🇺🇸
Aurora, Colorado, United States
H. Lee Moffitt Cancer Center & Research Institute
🇺🇸
Tampa, Florida, United States
University Of Miami - Miller School Of Medicine, Sylvester Comprehensive Cancer Center
🇺🇸
Miami, Florida, United States
Dana Farber Cancer Institute/ Boston Children's Hospital
🇺🇸
Boston, Massachusetts, United States
Roswell Park Cancer Institute
🇺🇸
Buffalo, New York, United States
Weill Cornell Medical College - New York-Presbyterian Hospital
🇺🇸
New York, New York, United States
Icahn School of Medicine at Mount Sinai
🇺🇸
New York, New York, United States
Herbert Irving Comprehensive Cancer Center-Columbia University Medical Center
🇺🇸
New York, New York, United States
University of North Carolina at Chapel Hill
🇺🇸
Chapel Hill, North Carolina, United States
Ohio State University Medical Center
🇺🇸
Columbus, Ohio, United States
Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
Texas Oncology - Baylor Charles A. Simmons Cancer Center
🇺🇸
Dallas, Texas, United States
Stephenson Cancer Center
🇺🇸
Oklahoma City, Oklahoma, United States
The University of Texas MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Oxford Centre for Respiratory Medicine Churchill Hospital, Oxford University Hospitals NHS Trust
🇬🇧
Oxford, United Kingdom
Medical College of WI Froedtert Hospital
🇺🇸
Milwaukee, Wisconsin, United States
Montefiore Medical Center
🇺🇸
Bronx, New York, United States