A Phase 1/2, Open-label Randomized Study of Ulocuplumab (BMS-936564) in Combination With Low Dose Cytarabine in Subjects With Newly Diagnosed Acute Myeloid Leukemia
Overview
- Phase
- Phase 1
- Intervention
- BMS-936564
- Conditions
- Leukemia
- Sponsor
- Bristol-Myers Squibb
- Enrollment
- 70
- Locations
- 16
- Primary Endpoint
- Number of Participants With >= Grade 3 AEs - Phase 1
- Status
- Terminated
- Last Updated
- 4 years ago
Overview
Brief Summary
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).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Newly Diagnosed Acute Myeloid Leukemia (AML)
- •Considered inappropriate for intensive remission induction therapy by an investigator
- •Not eligible for stem cell transplantation
Exclusion Criteria
- •Acute promyelocytic leukemia
- •Current Myelodysplastic syndrome only subjects
- •Unstable angina or uncontrolled congestive heart failure
- •Any other malignancy, excluding basal or squamous cell carcinoma of the skin, in situ melanoma, cervical carcinoma in situ, localized prostate cancer, or superficial bladder cancer stage 0, from which the subject has not been disease-free for at least 3 years
- •Respiratory disease requiring continuous supplemental oxygen
- •Other protocol defined inclusion/exclusion criteria could apply
Arms & Interventions
low dose Cytarabine only
Low Dose Cytarabine only Phase 2 (expansion cohort)
Intervention: BMS-936564
Ulocuplumab + low dose Cytarabine
Ulocuplumab + low dose Cytarabine (LDAC) Phase 1 (escalation cohort) - closed for enrollment
Intervention: BMS-936564
Ulocuplumab + low dose Cytarabine
Ulocuplumab + low dose Cytarabine (LDAC) Phase 1 (escalation cohort) - closed for enrollment
Intervention: Cytarabine
Ulocuplumab Dose A + low dose Cytarabine
Ulocuplumab Dose A + low dose Cytarabine Phase 2 (expansion cohort)
Intervention: BMS-936564
low dose Cytarabine only
Low Dose Cytarabine only Phase 2 (expansion cohort)
Intervention: Cytarabine
Ulocuplumab Dose A + low dose Cytarabine
Ulocuplumab Dose A + low dose Cytarabine Phase 2 (expansion cohort)
Intervention: Cytarabine
Ulocuplumab Dose B + low dose Cytarabine
Ulocuplumab Dose B + low dose Cytarabine Phase 2 (expansion cohort)
Intervention: BMS-936564
Ulocuplumab Dose B + low dose Cytarabine
Ulocuplumab Dose B + low dose Cytarabine Phase 2 (expansion cohort)
Intervention: Cytarabine
Outcomes
Primary Outcomes
Number of Participants With >= Grade 3 AEs - Phase 1
Time Frame: From first dose to 30 days post last dose
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).
Number of Participants With Dose-Limiting Toxicities (DLTs) in Treatment Cycle 1 - Phase 1
Time Frame: From first dose to end of cycle 1 (28 days)
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).
Number of Participants With Adverse Events (AEs) - Phase 1
Time Frame: From first dose to 30 days post last dose
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).
Number of Deaths - Phase 1
Time Frame: From first dose to 30 days post last dose
The number of participants who died.
Number of Participants With AEs Leading to Discontinuation - Phase 1
Time Frame: From first dose to 30 days post last dose
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).
Number of Participants With Serious Adverse Events (SAEs) - Phase 1
Time Frame: From first dose to 30 days post last dose
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).
Number of Participants With Laboratory Abnormalities - Phase 1
Time Frame: From first dose to 30 days post last dose
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
Best Overall Response (BOR) - Phase 2
Time Frame: From first dose until a minimum follow-up of up to 2 months
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
Secondary Outcomes
- Number of Deaths- Phase 2(From first dose until a minimum follow-up of up to 2 months)
- Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2(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))
- Best Overall Response (BOR) - Phase 1(From first dose until a minimum follow-up of up to 2 months)
- Number of Participants With AEs - Phase 2(From first dose until a minimum follow-up of up to 2 months)
- Number of Participants With AEs Leading to Discontinuation - Phase 2(From first dose until a minimum follow-up of up to 2 months)
- Number of Participants With SAEs - Phase 2(From first dose until a minimum follow-up of up to 2 months)
- Number of Participants With Laboratory Abnormalities - Phase 2(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(From first dose until a minimum follow-up of up to 2 months)
- Maximum Observed Serum Concentration (Cmax) - Phases 1 and 2(Cycle 1 Day 1)
- Time of Maximum Observed Ulocuplumab Serum Concentration (Tmax) - Phases 1 and 2(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(Cycle 1 Day 1)
- Area Under the Ulocuplumab Concentration-time Curve in One Dosing Interval [AUC(TAU)] - Phases 1 and 2(Cycle 1 Day 1)
- Area Under the Ulocuplumab Concentration-time Curve From Time Zero to Infinity [AUC(INF)] - Phases 1 and 2(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(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(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(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(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(From first dose until a minimum follow-up of up to 2 months)
- Total Body Clearance of Ulocuplumab (CLT) - Phases 1 and 2(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))
- 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(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(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(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(From first dose until a minimum follow-up of up to 2 months)
- Overall Survival (OS) - Phases 1 and 2(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(From first dose until a minimum follow-up of up to 2 months)