E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects with Newly Diagnosed Acute Myeloid Leukemia |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000886 |
E.1.2 | Term | Acute myeloid leukemia |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The purpose of this study is to determine the safety and effectiveness of ulocuplumab (ulo) in combination with low dose cytarabine in the treatment of Newly Diagnosed Acute Myeloid Leukemia (AML). |
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E.2.2 | Secondary objectives of the trial |
-characterize the immunogenicity of ulo, and the PK profiles of ulo combined with LDAC
-evaluate the effects of ulo on ECG intervals, including QTc intervals
-assess overall survival (OS) in subjects treated with ulo 800 mg or 1000 mg combined with LDAC
-Phase 1-escalation: evaluate the preliminary efficacy on the basis of objective response in subjects treated with ulo combined with LDAC
-Phase 2-expansion:
*assess the safety and tolerability of ulo in subjects treated with ulo at two different dose levels 800 mg and 1000 mg combined with LDAC
*assess rates of overall remission (OR=PR+CR+CRi) as well as duration of complete remission (CR/CRi) in subjects treated with ulo at two different dose levels 800 mg and 1000 mg combined with LDAC
*assess efficacy (in terms of rates of CR/CRi and OR and duration of remission, respectively, in subjects treated with LDAC alone, to compare with historical controls of LDAC in the same patient population. OS will be assessed too in this group |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Additional research is optional for all study participants, except where retention and/or collection is prohibited by local laws or regulations, ethics committees, or institutional requirements.
This collection for additional research is intended to expand the translational R&D capability at Bristol-Myers Squibb, and will support as yet undefined research aims that will advance our understanding of disease and options for treatment. It may also be used to support health authority requests for analysis, and advancement of pharmacodiagnostic development to better target drugs to the right patients. This may also include genetic/genomic exploration aimed at exploring disease pathways, progression and response to treatment etc.
See also 5.10.1 of the main protocol |
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E.3 | Principal 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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E.4 | Principal exclusion criteria |
• Acute promyelocytic leukemia
• Current Myelodysplastic syndrome |
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase 1 (escalation cohort):
• Number of patients experiencing a ulocuplumab-related dose limiting toxicity (DLT) during the DLT evaluation period based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03)
• Number of Adverse Events (AEs)
• Number of Grade 3 or higher Adverse Events (AEs)
• Number of Adverse Events (AEs) leading to discontinuation
• Number of Serious Adverse Events (SAEs)
• Number of Adverse Events (AEs) leading to death
• Number of Laboratory Abnormalities
Phase 2 (expansion cohort) :
• Overall response based on the Rate of Complete Remission (CR/CRi)
Complete Remission (CR), Complete Remission with incomplete blood count recovery (CRi), Rate of Complete Remission (CR/CRi) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
For all end points: up to 30 days after discontinuation of treatment |
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E.5.2 | Secondary end point(s) |
1) anti-drug antibody(ADA) positive for ulocuplumab
2) Maximum observed serum concentration (Cmax)
3) Trough observed serum concentration (Ctrough)
4) Time of maximum observed ulocuplumab serum concentration (Tmax)
5) Area under the ulocuplumab concentration-time curve from time zero to the last quantifiable concentration (AUC(0-T))
6) Area under the ulocuplumab concentration-time curve in one dosing interval (AUC{TAU})
7) Area under the ulocuplumab concentration-time curve from time zero to infinity (AUC(INF))
8) Elimination half life (T-HALF)
9) Total body clearance (CLT) of ulocuplumab
10) Volume of distribution at steady state (Vss)
11) Change from Baseline in electrocardiogram(ECG) intervals
12) Overall Remission (OR) as determined by investigator assessment using AML response criteria
13) Duration of complete Remission (CR/CRi) as determined by investigator assessment using AML response criteria
Complete Remission (CR), Complete Remission with incomplete blood count recovery (CRi)
14) Overall Survival (OS)
Overall survival: Defined as the time between the date of randomization and the date of death due to any cause
Phase 1 (escalation cohort)
15) Investigator assessed best overall response(BOR) using AML response criteria
Phase 2 (expansion cohort)
16) Number of Adverse Events (AEs)
17) Number of Serious Adverse Events (SAEs)
18) Number of Adverse Events (AEs) leading to discontinuation
19) Number of Adverse Events (AEs) leading to death
20) Number of Laboratory Abnormalities |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
up to 30 days after discontinuation of treatment for all endpoints except
11)Baseline up to 30 days after discontinuation of treatment
14)Up to 2 years |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Biomarker Assessments, Immunogenicity Assessments |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
escalation cohort to assess the safety and tolerability of ulocuplumab in combination with LDAC |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Brazil |
Canada |
Hong Kong |
Israel |
Japan |
Korea, Republic of |
Taiwan |
United States |
France |
Romania |
Italy |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The last visit for each subject will be defined as the end of follow up visit which is no less than 30 days after the subject’s end-of-treatment visit. The study will end after the last subject completes the last visit. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 7 |