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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02305563
Recruitment Status : Terminated (Business objectives have changed, slow accrual, the standard of care for the patient population changed and we were unable to accrue any longer.)
First Posted : December 2, 2014
Results First Posted : September 16, 2021
Last Update Posted : September 16, 2021
Sponsor:
Information provided by (Responsible Party):
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).

Condition or disease Intervention/treatment Phase
Leukemia Drug: BMS-936564 Drug: Cytarabine Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 27, 2015
Actual Primary Completion Date : June 4, 2019
Actual Study Completion Date : June 4, 2019


Arm Intervention/treatment
Experimental: Ulocuplumab + low dose Cytarabine
Ulocuplumab + low dose Cytarabine (LDAC) Phase 1 (escalation cohort) - closed for enrollment
Drug: BMS-936564
Other Names:
  • Ulocuplumab
  • MDX-1338

Drug: Cytarabine
Experimental: Ulocuplumab Dose A + low dose Cytarabine
Ulocuplumab Dose A + low dose Cytarabine Phase 2 (expansion cohort)
Drug: BMS-936564
Other Names:
  • Ulocuplumab
  • MDX-1338

Drug: Cytarabine
Experimental: Ulocuplumab Dose B + low dose Cytarabine
Ulocuplumab Dose B + low dose Cytarabine Phase 2 (expansion cohort)
Drug: BMS-936564
Other Names:
  • Ulocuplumab
  • MDX-1338

Drug: Cytarabine
low dose Cytarabine only
Low Dose Cytarabine only Phase 2 (expansion cohort)
Drug: BMS-936564
Other Names:
  • Ulocuplumab
  • MDX-1338

Drug: Cytarabine



Primary Outcome Measures :
  1. 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).

  2. 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).


  3. 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).


  4. 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).


  5. 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).


  6. Number of Deaths - Phase 1 [ Time Frame: From first dose to 30 days post last dose ]
    The number of participants who died.

  7. 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


  8. 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 Outcome Measures :
  1. Best Overall Response (BOR) - Phase 1 [ Time Frame: 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.

  2. Number of Participants With AEs - Phase 2 [ Time Frame: 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).


  3. Number of Participants With AEs Leading to Discontinuation - Phase 2 [ Time Frame: 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).


  4. Number of Participants With SAEs - Phase 2 [ Time Frame: 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).


  5. Number of Deaths- Phase 2 [ Time Frame: 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).


  6. Number of Participants With Laboratory Abnormalities - Phase 2 [ Time Frame: 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).


  7. Number of Participants With Anti-drug Antibodies (ADA) Positive for Ulocuplumab - Phases 1 and 2 [ Time Frame: 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

  8. Maximum Observed Serum Concentration (Cmax) - Phases 1 and 2 [ Time Frame: 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


  9. Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2 [ 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) ]

    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


  10. Time of Maximum Observed Ulocuplumab Serum Concentration (Tmax) - Phases 1 and 2 [ Time Frame: Cycle 1 Day 1 ]

    The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration.

    EOT = end of treatment


  11. Area Under the Ulocuplumab Concentration-time Curve From Time Zero to the Last Quantifiable Concentration [AUC(0-T)] - Phases 1 and 2 [ Time Frame: 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


  12. Area Under the Ulocuplumab Concentration-time Curve in One Dosing Interval [AUC(TAU)] - Phases 1 and 2 [ Time Frame: 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


  13. Area Under the Ulocuplumab Concentration-time Curve From Time Zero to Infinity [AUC(INF)] - Phases 1 and 2 [ 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) ]

    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


  14. Elimination Half-life (T-HALF) - Phases 1 and 2 [ 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) ]

    The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration.

    EOT = end of treatment

    T-HALF determined as 0.693/λz


  15. Total Body Clearance of Ulocuplumab (CLT) - Phases 1 and 2 [ 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) ]

    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


  16. Volume of Distribution at Steady State (Vss) - Phases 1 and 2 [ 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) ]

    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


  17. 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 [ Time Frame: 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


  18. 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 [ Time Frame: 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.

  19. Rate of Complete Remission (CR/CRi) and Overall Rate of Remission in Participants Treated With LDAC Only - Phase 2 [ Time Frame: 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


  20. Duration of Response in Participants With CR/CRi Treated With LDAC Only - Phase 2 [ Time Frame: 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.

  21. Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2 [ Time Frame: 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)


  22. Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2 [ Time Frame: 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)


  23. Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2 [ Time Frame: 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)


  24. Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2 [ Time Frame: 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)


  25. Overall Survival (OS) - Phases 1 and 2 [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02305563


Locations
Show Show 38 study locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Layout table for investigator information
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  Study Documents (Full-Text)

Documents provided by Bristol-Myers Squibb:
Study Protocol  [PDF] July 27, 2017
Statistical Analysis Plan  [PDF] September 29, 2017

Additional Information:
Layout table for additonal information
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT02305563    
Other Study ID Numbers: CA212-016
First Posted: December 2, 2014    Key Record Dates
Results First Posted: September 16, 2021
Last Update Posted: September 16, 2021
Last Verified: August 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid
Cytarabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs