An Investigational Immuno-therapy Study of Ulocuplumab in Combination With Low Dose Cytarabine in Patients With Newly Diagnosed Acute Myeloid Leukemia

Phase 1

Terminated

• Conditions: Leukemia
• Interventions: Drug: BMS-936564; Drug: Cytarabine

• Registration Number: NCT02305563
• Lead Sponsor: Bristol-Myers Squibb

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-11-27
• Study First Submitted QC: 2014-11-27
• Study First Posted: 2014-12-02
• Study Start: 2015-01-27
• Primary Completion: 2019-06-04
• Study Completion: 2019-06-04
• Results First Submitted: 2020-06-03
• Status Verified: 2021-08
• Results First Submitted QC: 2021-08-18
• Last Update Submitted: 2021-08-18
• Results First Posted: 2021-09-16
• Last Update Posted: 2021-09-16

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

• Newly Diagnosed Acute Myeloid Leukemia (AML)
• Considered inappropriate for intensive remission induction therapy by an investigator
• Not eligible for stem cell transplantation

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ulocuplumab Dose A + low dose Cytarabine	Cytarabine	Ulocuplumab Dose A + low dose Cytarabine Phase 2 (expansion cohort)
Ulocuplumab Dose A + low dose Cytarabine	BMS-936564	Ulocuplumab Dose A + low dose Cytarabine Phase 2 (expansion cohort)
low dose Cytarabine only	BMS-936564	Low Dose Cytarabine only Phase 2 (expansion cohort)
Ulocuplumab + low dose Cytarabine	BMS-936564	Ulocuplumab + low dose Cytarabine (LDAC) Phase 1 (escalation cohort) - closed for enrollment
Ulocuplumab Dose B + low dose Cytarabine	Cytarabine	Ulocuplumab Dose B + low dose Cytarabine Phase 2 (expansion cohort)
Ulocuplumab Dose B + low dose Cytarabine	BMS-936564	Ulocuplumab Dose B + low dose Cytarabine Phase 2 (expansion cohort)
low dose Cytarabine only	Cytarabine	Low Dose Cytarabine only Phase 2 (expansion cohort)
Ulocuplumab + low dose Cytarabine	Cytarabine	Ulocuplumab + low dose Cytarabine (LDAC) Phase 1 (escalation cohort) - closed for enrollment

Primary Outcome Measures

Name	Time	Method
Number of Participants With >= Grade 3 AEs - Phase 1	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	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	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	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	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	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	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	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 Outcome Measures

Name	Time	Method
Number of Deaths- Phase 2	From first dose until a minimum follow-up of up to 2 months	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).
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)	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
Best Overall Response (BOR) - Phase 1	From first dose until a minimum follow-up of up to 2 months	Investigator assessed best overall response prior to the initiation of any alternative therapy for Phase 1 participants.
Number of Participants With AEs - Phase 2	From first dose until a minimum follow-up of up to 2 months	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 Participants With AEs Leading to Discontinuation - Phase 2	From first dose until a minimum follow-up of up to 2 months	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 SAEs - Phase 2	From first dose until a minimum follow-up of up to 2 months	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 2	From first dose until a minimum follow-up of up to 2 months	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).
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	Serum samples from ulocuplumab treated participants were evaluated for the presence of anti-ulocuplumab antibodies
Maximum Observed Serum Concentration (Cmax) - Phases 1 and 2	Cycle 1 Day 1	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 of Maximum Observed Ulocuplumab Serum Concentration (Tmax) - Phases 1 and 2	Cycle 1 Day 1	The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration.; EOT = end of treatment
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	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
Area Under the Ulocuplumab Concentration-time Curve in One Dosing Interval [AUC(TAU)] - Phases 1 and 2	Cycle 1 Day 1	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
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)	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
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)	The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration.; EOT = end of treatment; T-HALF determined as 0.693/λz
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)	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
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	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
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 ECG endpoints; Heart rate measured in beats per minute (bpm)
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	Change from baseline of ECG endpoints; PR interval measured in milliseconds (msec)
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)	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
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	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.
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	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
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 ECG endpoints; QRS interval measured in milliseconds (msec)
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	Change from baseline of ECG endpoints; QT interval measured in milliseconds (msec)
Overall Survival (OS) - Phases 1 and 2	From first dose until a minimum follow-up of up to 2 months	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.
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	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.

Trial Locations

Locations (16)

Ucla Center Health Sci; 🇺🇸 Los Angeles, California, United States

Fundacao Pio Xii Hosp Cancer De Barretos; 🇧🇷 Barretos, Sao Paulo, Brazil

Liga Paranaense De Combate Ao Cancer Erasto Gaertner; 🇧🇷 Curitiba, Parana, Brazil

IEP Sao Lucas; 🇧🇷 Sao Paulo, Brazil

Azienda Ospedaliera Di Rilievo Nazionale A. Cardarelli; 🇮🇹 Napoli, Italy

Local Institution; 🇨🇳 Taoyuan City, Taiwan

Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele; 🇮🇹 Catania, Italy

Instituto Do Cancer Mae De Deus / Cor Hospital Mae De Deus; 🇧🇷 Porto Alegre, RIO Grande DO SUL, Brazil

Cleveland Clinic Taussig Cancer Center; 🇺🇸 Cleveland, Ohio, United States

NYU Langone Medical Center; 🇺🇸 New York, New York, United States

Norton Cancer Institute; 🇺🇸 Louisville, Kentucky, United States

Duke University Adult Bone Marrow Transplant Clinic; 🇺🇸 Durham, North Carolina, United States

University Of Cincinnati; 🇺🇸 Cincinnati, 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

UF Health Cancer Center at Orlando Health; 🇺🇸 Orlando, Florida, United States