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

Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02305563
• Other study ID #: CA212-016
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: January 27, 2015
• Est. completion date: June 4, 2019

Study information

• Verified date: August 2021
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 70
• Est. completion date: June 4, 2019
• Est. primary completion date: June 4, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid, Acute

Intervention

Drug:
• BMS-936564

• Cytarabine

Locations

Country	Name	City	State
Brazil	Fundacao Pio Xii Hosp Cancer De Barretos	Barretos	Sao Paulo
Brazil	Liga Paranaense De Combate Ao Cancer Erasto Gaertner	Curitiba	Parana
Brazil	Instituto Do Cancer Mae De Deus / Cor Hospital Mae De Deus	Porto Alegre	RIO Grande DO SUL
Brazil	IEP Sao Lucas	Sao Paulo
Brazil	Local Institution	Sao Paulo
Brazil	Local Institution	Sao Paulo
Canada	Local Institution	Halifax	Nova Scotia
China	Local Institution	Hong Kong
Israel	Local Institution	Jerusalem
Israel	Local Institution	Tel Aviv
Italy	Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele	Catania
Italy	Local Institution	Milan
Italy	Azienda Ospedaliera Di Rilievo Nazionale A. Cardarelli	Napoli
Italy	Local Institution	Roma
Japan	Local Institution	Bunkyo-ku	Tokyo
Japan	Local Institution	Fukuyama-shi	Hiroshima
Japan	Local Institution	Hirakata-shi	Osaka
Japan	Local Institution	Isehara	Kanagawa
Japan	Local Institution	Nagoya-shi	Aichi
Japan	Local Institution	Shinagawa-ku	Tokyo
Japan	Local Institution	Shinjuku-Ku	Tokyo
Japan	Local Institution	Tachikawa	Tokyo
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Romania	Local Institution	Bucharest
Taiwan	Local Institution	Kaohsiung
Taiwan	Local Institution	New Taipei City
Taiwan	Local Institution	New Taipei City
Taiwan	Local Institution	Taoyuan City
United States	University Of Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Duke University Adult Bone Marrow Transplant Clinic	Durham	North Carolina
United States	The University Of Texas MD Anderson Cancer Center	Houston	Texas
United States	Ucla Center Health Sci	Los Angeles	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Froedtert Hospital & Medical College of Wisconsin	Milwaukee	Wisconsin
United States	NYU Langone Medical Center	New York	New York
United States	UF Health Cancer Center at Orlando Health	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Brazil,  Canada,  China,  Israel,  Italy,  Japan,  Korea, Republic of,  Romania,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	From first dose to end of cycle 1 (28 days)
Primary	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).	From first dose to 30 days post last dose
Primary	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).	From first dose to 30 days post last dose
Primary	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).	From first dose to 30 days post last dose
Primary	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).	From first dose to 30 days post last dose
Primary	Number of Deaths - Phase 1	The number of participants who died.	From first dose to 30 days post last dose
Primary	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	From first dose to 30 days post last dose
Primary	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	From first dose until a minimum follow-up of up to 2 months
Secondary	Best Overall Response (BOR) - Phase 1	Investigator assessed best overall response prior to the initiation of any alternative therapy for Phase 1 participants.	From first dose until a minimum follow-up of up to 2 months
Secondary	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).	From first dose until a minimum follow-up of up to 2 months
Secondary	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).	From first dose until a minimum follow-up of up to 2 months
Secondary	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).	From first dose until a minimum follow-up of up to 2 months
Secondary	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).	From first dose until a minimum follow-up of up to 2 months
Secondary	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).	From first dose until a minimum follow-up of up to 2 months
Secondary	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	From first dose until a minimum follow-up of up to 2 months
Secondary	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	Cycle 1 Day 1
Secondary	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	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)
Secondary	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	Cycle 1 Day 1
Secondary	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	Cycle 1 Day 1
Secondary	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	Cycle 1 Day 1
Secondary	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/?z; Measure type and method of dispersion are Geometric mean and %CV, respectively	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)
Secondary	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/?z	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)
Secondary	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	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)
Secondary	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	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)
Secondary	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	From first dose until a minimum follow-up of up to 2 months
Secondary	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.	From first dose until a minimum follow-up of up to 2 months
Secondary	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	From first dose until a minimum follow-up of up to 2 months
Secondary	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.	From first dose until a minimum follow-up of up to 2 months
Secondary	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)	From first dose until a minimum follow-up of up to 2 months
Secondary	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)	From first dose until a minimum follow-up of up to 2 months
Secondary	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)	From first dose until a minimum follow-up of up to 2 months
Secondary	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)	From first dose until a minimum follow-up of up to 2 months
Secondary	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.	From first dose until a minimum follow-up of up to 2 months

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