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
* 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
Brief Title
Magrolimab Monotherapy or Magrolimab in Combination With Azacitidine in Participants With Hematological Malignancies
Categories
Completion Date
Completion Date Type
Actual
Conditions
Hematological Malignancies
Eligibility Criteria
Key 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.
* 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.
Inclusion Criteria
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.
Inclusion/
* 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.
Inclusion/
Gender
All
Gender Based
false
Keywords
CD47
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT03248479
Org Class
Industry
Org Full Name
Gilead Sciences
Org Study Id
5F9005
Overall Status
Terminated
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 1b Trial of Magrolimab Monotherapy or Magrolimab in Combination With Azacitidine in Patients With Hematological Malignancies
Primary Outcomes
Outcome Description
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.
Outcome Measure
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
Outcome Time Frame
Up to 4 years
Outcome Description
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.
Outcome Measure
Complete Remission (CR) Rate For Participants With AML
Outcome Time Frame
Up to 5 years
Outcome Description
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%.
Outcome Measure
CR Rate for Participants With MDS
Outcome Time Frame
Up to 5 years
Outcome Description
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.
Outcome Measure
Percentage of Participants With Red Blood Cell (RBC) Transfusion Independence for Participants With Low-Risk MDS
Outcome Time Frame
Up to 8 weeks
Secondary Ids
Secondary Id
2017-000678-12
Secondary Outcomes
Outcome Time Frame
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
Outcome Measure
Serum Concentration for Magrolimab in TN/U AML and TN MDS Participants
Outcome Description
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.
Outcome Time Frame
Up to 5 years
Outcome Measure
Percentage of Participants Who Developed Anti-Magrolimab Antibodies
Outcome Description
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.
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.
Outcome Time Frame
Up to 5 years
Outcome Measure
Duration of Complete Remission (DCR) in Participants With AML and MDS
Outcome Description
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.
Percentages were rounded off.
Outcome Time Frame
Up to 5 years
Outcome Measure
Percentage of MDS Participants With Objective Response Rate (ORR) as Defined by IWG 2006 MDS Response Criteria
Outcome Description
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%.
Outcome Time Frame
Up to 5 years
Outcome Measure
Percentage of AML Participants With Objective Response Rate (ORR)
Outcome Description
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).
Outcome Time Frame
Up to 5 years
Outcome Measure
Percentage of Participants With Complete Remission With Partial Hematologic Recovery (CRh) for AML Participants
Outcome Description
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.
KM estimates were used in the outcome measure analysis.
Outcome Time Frame
Up to 5 years
Outcome Measure
Duration of Response (DOR) for Participants With AML
Outcome Description
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.
KM estimates were used in the outcome measure analysis.
Outcome Time Frame
Up to 5 years
Outcome Measure
Duration of Response for Participants With MDS
Outcome Description
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.
KM estimates were used in the outcome measure analysis.
Outcome Time Frame
Up to 5 years
Outcome Measure
Overall Survival (OS) for Participants With AML or MDS
Outcome Description
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.
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.
Outcome Time Frame
Up to 5 years
Outcome Measure
Progression Free Survival (PFS) for Participants With AML or MDS
Outcome Description
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.
Outcome Time Frame
Up to 5 years
Outcome Measure
Relapse Free Survival (RFS) for Participants With AML or MDS
Outcome Description
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.
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.
Outcome Time Frame
Up to 5 years
Outcome Measure
Event Free Survival (EFS) for Participants With AML or MDS
Outcome Time Frame
Baseline and Day 1
Outcome Measure
Change From Baseline in Hemoglobin on Therapy
Outcome Time Frame
Up to 12 Weeks
Outcome Measure
12-week RBC Transfusion Independence Rates
Outcome Description
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.
Outcome Time Frame
Up to 5 years
Outcome Measure
Minimal Residual Disease (MRD) Negative Response Rate
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Amit Verma
Investigator Email
amit.verma@einsteinmed.org
Investigator Phone
718-405-8505 / 718-904-2900