An Investigational Immuno-therapy Study of Ulocuplumab in Combination With Low Dose Cytarabine in Patients With Newly Diagnosed Acute Myeloid Leukemia
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| ClinicalTrials.gov Identifier: NCT02305563 |
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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
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Leukemia | Drug: BMS-936564 Drug: Cytarabine | Phase 1 Phase 2 |
| 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 |
|---|---|
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Experimental: Ulocuplumab + low dose Cytarabine
Ulocuplumab + low dose Cytarabine (LDAC) Phase 1 (escalation cohort) - closed for enrollment
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Drug: BMS-936564
Other Names:
Drug: Cytarabine |
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Experimental: Ulocuplumab Dose A + low dose Cytarabine
Ulocuplumab Dose A + low dose Cytarabine Phase 2 (expansion cohort)
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Drug: BMS-936564
Other Names:
Drug: Cytarabine |
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Experimental: Ulocuplumab Dose B + low dose Cytarabine
Ulocuplumab Dose B + low dose Cytarabine Phase 2 (expansion cohort)
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Drug: BMS-936564
Other Names:
Drug: Cytarabine |
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low dose Cytarabine only
Low Dose Cytarabine only Phase 2 (expansion cohort)
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Drug: BMS-936564
Other Names:
Drug: Cytarabine |
- 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 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 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 Deaths - Phase 1 [ Time Frame: From first dose to 30 days post last dose ]The number of participants who died.
- 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
- 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.
- 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).
- 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).
- 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).
- 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).
- 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).
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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.
- 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
- 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.
- 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)
- 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)
- 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)
- 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)
- 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.
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.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
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
Show 38 study locations
| Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
Documents provided by Bristol-Myers Squibb:
| 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 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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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 |