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

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

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 Overview

• Status: Terminated
• Conditions: Leukemia
• Intervention / Treatment: Drug: Cytarabine; Drug: BMS-936564

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo, Brazil, 01246-000
    • Local Institution
  • Sao Paulo, Brazil, 01236-030
    • IEP São Lucas
  • Sao Paulo, Brazil, 05651-901
    • Local Institution
  • Parana
    • Curitiba, Parana, Brazil, 81520-060
      • Liga Paranaense De Combate Ao Cancer Erasto Gaertner
  • RIO Grande DO SUL
    • Porto Alegre, RIO Grande DO SUL, Brazil, 90110-270
      • Instituto Do Cancer Mae De Deus / Cor Hospital Mae De Deus
  • Sao Paulo
    • Barretos, Sao Paulo, Brazil, 14784-400
      • Fundacao Pio Xii Hosp Cancer De Barretos
• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Local Institution
• China
  • Hong Kong, China
    • Local Institution
• Israel
  • Jerusalem, Israel, 91031
    • Local Institution
  • Tel Aviv, Israel, 94239
    • Local Institution
• Italy
  • Catania, Italy, 95123
    • Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele
  • Milan, Italy, 20162
    • Local Institution
  • Napoli, Italy, 80131
    • Azienda Ospedaliera Di Rilievo Nazionale A. Cardarelli
  • Roma, Italy, 00133
    • Local Institution
• Japan
  • Aichi
    • Nagoya-shi, Aichi, Japan, 4600001
      • Local Institution
  • Hiroshima
    • Fukuyama-shi, Hiroshima, Japan, 7200001
      • Local Institution
  • Kanagawa
    • Isehara, Kanagawa, Japan, 2591193
      • Local Institution
  • Osaka
    • Hirakata-shi, Osaka, Japan, 5731191
      • Local Institution
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 1138677
      • Local Institution
    • Shinagawa-ku, Tokyo, Japan, 1418625
      • Local Institution
    • Shinjuku-Ku, Tokyo, Japan, 1608582
      • Local Institution
    • Tachikawa, Tokyo, Japan, 1900014
      • Local Institution
• Korea, Republic of
  • Seoul, Korea, Republic of, 06591
    • Local Institution
  • Seoul, Korea, Republic of, 06351
    • Local Institution
• Romania
  • Bucharest, Romania, 020125
    • Local Institution
• Taiwan
  • Kaohsiung, Taiwan, 833
    • Local Institution
  • New Taipei City, Taiwan, 235
    • Local Institution
  • New Taipei City, Taiwan, 25173
    • Local Institution
  • Taoyuan City, Taiwan, 33305
    • Local Institution
• United States
  • California
    • Los Angeles, California, United States, 90095-3075
      • Ucla Center Health Sci
  • Florida
    • Orlando, Florida, United States, 32806
      • UF Health Cancer Center at Orlando Health
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Norton Cancer Institute
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Adult Bone Marrow Transplant Clinic
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Hospital & Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ulocuplumab + low dose Cytarabine; Ulocuplumab + low dose Cytarabine (LDAC) Phase 1 (escalation cohort) - closed for enrollment	Drug: Cytarabine; Drug: BMS-936564; Other Names: Ulocuplumab; MDX-1338
Experimental: Ulocuplumab Dose A + low dose Cytarabine; Ulocuplumab Dose A + low dose Cytarabine Phase 2 (expansion cohort)	Drug: Cytarabine; Drug: BMS-936564; Other Names: Ulocuplumab; MDX-1338
Experimental: Ulocuplumab Dose B + low dose Cytarabine; Ulocuplumab Dose B + low dose Cytarabine Phase 2 (expansion cohort)	Drug: Cytarabine; Drug: BMS-936564; Other Names: Ulocuplumab; MDX-1338
Other: low dose Cytarabine only; Low Dose Cytarabine only Phase 2 (expansion cohort)	Drug: Cytarabine; Drug: BMS-936564; Other Names: Ulocuplumab; MDX-1338

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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
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
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
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
Number of Deaths - Phase 1	The number of participants who died.	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	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	From first dose until a minimum follow-up of up to 2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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)
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
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
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
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	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	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	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	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	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.	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	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.	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)	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)	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)	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)	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.	From first dose until a minimum follow-up of up to 2 months

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2015
• Primary Completion (Actual): June 4, 2019
• Study Completion (Actual): June 4, 2019

Study Registration Dates

• First Submitted: November 27, 2014
• First Submitted That Met QC Criteria: November 27, 2014
• First Posted (Estimate): December 2, 2014

Study Record Updates

• Last Update Posted (Actual): September 16, 2021
• Last Update Submitted That Met QC Criteria: August 18, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia, Myeloid; Leukemia; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Cytarabine
• Other Study ID Numbers: CA212-016

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No