The purpose of this study is to determine the safety and effectiveness of ulocuplumab in combination with low dose cytarabine in the treatment of Newly Diagnosed Acute Myeloid Leukemia (AML).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
70
Number of Participants With Dose-Limiting Toxicities (DLTs) in Treatment Cycle 1 - Phase 1
Safety data evaluated for DLTs. DLTs and all other toxicities were defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03). DLTs were defined based upon events that were considered to be related to ulocuplumab in combination with LDAC and that occurred during the first cycle of drug administration (28 days).
Time frame: From first dose to end of cycle 1 (28 days)
Number of Participants With Adverse Events (AEs) - Phase 1
The number of participants with an on-study adverse event (AE). Safety data are evaluated for AEs, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03).
Time frame: From first dose to 30 days post last dose
Number of Participants With >= Grade 3 AEs - Phase 1
The number of participants with an on-study adverse event \>= Grade level 3. Safety data are evaluated for \>= Grade 3 AEs, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03).
Time frame: From first dose to 30 days post last dose
Number of Participants With AEs Leading to Discontinuation - Phase 1
The number of participants with an on-study adverse event (AE) leading to discontinuation. Safety data are evaluated for AEs leading to discontinuation, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03).
Time frame: From first dose to 30 days post last dose
Number of Participants With Serious Adverse Events (SAEs) - Phase 1
The number of participants with an on-study serious adverse event (SAE). Safety data are evaluated for SAEs, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03).
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Ucla Center Health Sci
Los Angeles, California, United States
UF Health Cancer Center at Orlando Health
Orlando, Florida, United States
Norton Cancer Institute
Louisville, Kentucky, United States
NYU Langone Medical Center
New York, New York, United States
Duke University Adult Bone Marrow Transplant Clinic
Durham, North Carolina, United States
University Of Cincinnati
Cincinnati, Ohio, United States
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States
The University Of Texas MD Anderson Cancer Center
Houston, Texas, United States
Froedtert Hospital & Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Liga Paranaense De Combate Ao Cancer Erasto Gaertner
Curitiba, Paraná, Brazil
...and 28 more locations
Time frame: From first dose to 30 days post last dose
Number of Deaths - Phase 1
The number of participants who died.
Time frame: From first dose to 30 days post last dose
Number of Participants With Laboratory Abnormalities - Phase 1
The number of participants with an on-study laboratory abnormality. Safety data are evaluated for laboratory abnormalities, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03). grades 1, 2, 3, 4, 5, unknown, with 5 being the worst outcome
Time frame: From first dose to 30 days post last dose
Best Overall Response (BOR) - Phase 2
The phase 2 primary endpoint was based on the rate of Complete Remission (CR/CRi) prior to the initiation of any alternative therapy (including any subsequent ulocuplumab 800 mg for participants in the LDAC alone arm). The phase 2 primary analysis was conducted after all participants had an opportunity for 6 months of follow-up. Complete remission rate: CR + CRi, confidence interval based on the Clopper and Pearson method. CR = complete response CRi = complete response, incomplete blood count
Time frame: From first dose until a minimum follow-up of up to 2 months
Best Overall Response (BOR) - Phase 1
Investigator assessed best overall response prior to the initiation of any alternative therapy for Phase 1 participants.
Time frame: From first dose until a minimum follow-up of up to 2 months
Number of Participants With AEs - Phase 2
The number of participants with an on-study adverse event (AE). Safety data are evaluated for AEs, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03).
Time frame: From first dose until a minimum follow-up of up to 2 months
Number of Participants With AEs Leading to Discontinuation - Phase 2
The number of participants with an on-study adverse event (AE) leading to discontinuation. Safety data are evaluated for AEs leading to discontinuation, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03).
Time frame: From first dose until a minimum follow-up of up to 2 months
Number of Participants With SAEs - Phase 2
The number of participants with an on-study serious adverse event (SAE). Safety data are evaluated for SAEs, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03).
Time frame: From first dose until a minimum follow-up of up to 2 months
Number of Deaths- Phase 2
The number of participants who died. Safety data are evaluated for deaths, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03).
Time frame: From first dose until a minimum follow-up of up to 2 months
Number of Participants With Laboratory Abnormalities - Phase 2
The number of participants with an on-study laboratory abnormality, assessed from Grade 1-4 Serum Chemistry, Electrolytes, and Hematology Laboratory Test results, with grade 4 being the worst. Safety data are evaluated for laboratory abnormalities, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03).
Time frame: From first dose until a minimum follow-up of up to 2 months
Number of Participants With Anti-drug Antibodies (ADA) Positive for Ulocuplumab - Phases 1 and 2
Serum samples from ulocuplumab treated participants were evaluated for the presence of anti-ulocuplumab antibodies
Time frame: From first dose until a minimum follow-up of up to 2 months
Maximum Observed Serum Concentration (Cmax) - Phases 1 and 2
The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration EOT = end of treatment Measure type and method of dispersion are Geometric mean and %CV, respectively
Time frame: Cycle 1 Day 1
Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2
The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration. EOT = end of treatment Measure type and method of dispersion are Geometric mean and %CV, respectively
Time frame: Days 1, 8, 15 for cycle 1; Days 8, 15 for cycle 2; Days 1, 8 for cycles 3-5; Day 1 every 4th cycle thereafter; EOT; 30 days post last dose (follow-up)
Time of Maximum Observed Ulocuplumab Serum Concentration (Tmax) - Phases 1 and 2
The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration. EOT = end of treatment
Time frame: Cycle 1 Day 1
Area Under the Ulocuplumab Concentration-time Curve From Time Zero to the Last Quantifiable Concentration [AUC(0-T)] - Phases 1 and 2
The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration. EOT = end of treatment AUC(0-T) calculated by log- and linear-trapezoidal summation Measure type and method of dispersion are Geometric mean and %CV, respectively
Time frame: Cycle 1 Day 1
Area Under the Ulocuplumab Concentration-time Curve in One Dosing Interval [AUC(TAU)] - Phases 1 and 2
The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration. EOT = end of treatment Measure type and method of dispersion are Geometric mean and %CV, respectively
Time frame: Cycle 1 Day 1
Area Under the Ulocuplumab Concentration-time Curve From Time Zero to Infinity [AUC(INF)] - Phases 1 and 2
The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration. EOT = end of treatment AUC(INF) calculated by summing AUC(0-T) and the extrapolated area, computed by the quotient Clast/λz Measure type and method of dispersion are Geometric mean and %CV, respectively
Time frame: Days 1, 8, 15 for cycles 1 and 2; Days 1, 8 for cycles 3-5; Day 1 every 4th cycle thereafter; EOT; 30 days post last dose (follow-up)
Elimination Half-life (T-HALF) - Phases 1 and 2
The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration. EOT = end of treatment T-HALF determined as 0.693/λz
Time frame: Days 1, 8, 15 for cycles 1 and 2; Days 1, 8 for cycles 3-5; Day 1 every 4th cycle thereafter; EOT; 30 days post last dose (follow-up)
Total Body Clearance of Ulocuplumab (CLT) - Phases 1 and 2
The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration. EOT = end of treatment CLT calculated by dividing the total dose of ulocuplumab by its corresponding AUC(INF) value Measure type and method of dispersion are Geometric mean and %CV, respectively
Time frame: Days 1, 8, 15 for cycles 1 and 2; Days 1, 8 for cycles 3-5; Day 1 every 4th cycle thereafter; EOT; 30 days post last dose (follow-up)
Volume of Distribution at Steady State (Vss) - Phases 1 and 2
The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration. EOT = end of treatment Measure type and method of dispersion are Geometric mean and %CV, respectively
Time frame: Days 1, 8, 15 for cycles 1 and 2; Days 1, 8 for cycles 3-5; Day 1 every 4th cycle thereafter; EOT; 30 days post last dose (follow-up)
Overall Rate of Remission in Participants Treated With Ulocuplumab at Two Different Dose Levels 800 mg and 1000 mg in Combination With LDAC - Phase 2
This phase 2 secondary endpoint was based on the rate of Overall Remission (OR=PR+CR +CRi) prior to the initiation of any alternative therapy (including any subsequent ulocuplumab 800 mg for participants in the LDAC alone arm). The phase 2 analysis was conducted after all participants had an opportunity for 6 months of follow-up. Overall remission rate: CR + CRi, + PR confidence interval based on the Clopper and Pearson method. CR = complete response CRi = complete response, incomplete blood count PR = partial remission
Time frame: From first dose until a minimum follow-up of up to 2 months
Duration of Response in Participants With CR/CRi Treated With Ulocuplumab at Two Different Dose Levels 800 mg and 1000 mg in Combination With LDAC - Phase 2
This phase 2 secondary endpoint was based on the duration of complete remission prior to the initiation of any alternative therapy (including any subsequent ulocuplumab 800 mg for participants in the LDAC alone arm). The phase 2 analysis was conducted after all participants had an opportunity for 6 months of follow-up.
Time frame: From first dose until a minimum follow-up of up to 2 months
Rate of Complete Remission (CR/CRi) and Overall Rate of Remission in Participants Treated With LDAC Only - Phase 2
This phase 2 secondary endpoint was based on the rate of Complete Remission (CR/CRi) and rate of Overall Remission (OR=PR+CR +CRi) prior to the initiation of any alternative therapy (including any subsequent ulocuplumab 800 mg for participants in the LDAC alone arm). The phase 2 analysis was conducted after all participants had an opportunity for 6 months of follow-up. Overall remission rate: CR + CRi, + PR confidence interval based on the Clopper and Pearson method. CR = complete response CRi = complete response, incomplete blood count PR = partial remission
Time frame: From first dose until a minimum follow-up of up to 2 months
Duration of Response in Participants With CR/CRi Treated With LDAC Only - Phase 2
This phase 2 secondary endpoint was based on the duration of complete remission prior to the initiation of any alternative therapy (including any subsequent ulocuplumab 800 mg for participants in the LDAC alone arm). The phase 2 analysis was conducted after all participants had an opportunity for 6 months of follow-up.
Time frame: From first dose until a minimum follow-up of up to 2 months
Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2
Change from baseline of ECG endpoints Heart rate measured in beats per minute (bpm)
Time frame: From first dose until a minimum follow-up of up to 2 months
Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2
Change from baseline of ECG endpoints PR interval measured in milliseconds (msec)
Time frame: From first dose until a minimum follow-up of up to 2 months
Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2
Change from baseline of ECG endpoints QRS interval measured in milliseconds (msec)
Time frame: From first dose until a minimum follow-up of up to 2 months
Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2
Change from baseline of ECG endpoints QT interval measured in milliseconds (msec)
Time frame: From first dose until a minimum follow-up of up to 2 months
Overall Survival (OS) - Phases 1 and 2
OS is defined as the time between the first date of treatment and the date of death due to any cause. A participant who has not died was be censored at the last known alive date.
Time frame: From first dose until a minimum follow-up of up to 2 months