Study to Evaluate the Safety and Tolerability of Weekly Intravenous (IV) Doses of BMS-906024 in Subjects With Acute T-cell Lymphoblastic Leukemia or T-cell Lymphoblastic Lymphoma

Study Overview
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Brief Summary
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The purpose of this study is to identify a safe and tolerable dose of BMS-906024, either alone or in combination with Dexamethasone in subjects with T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma who no longer respond to or have relapsed from standard therapies

Detailed Description
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Minimum Age: 10 years and older at selected sites

Official Title
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Phase 1 Ascending Multiple-Dose Study to Evaluate the Safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) of BMS-906024 in Subjects With Relapsed/Refractory T-cell Acute Lymphoblastic Leukemia or T-cell Lymphoblastic Lymphoma

Conditions
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Lymphoblastic Leukemia, Acute T-cell, Precursor T-Cell Lymphoblastic Lymphoma

Intervention / Treatment
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* Drug: BMS-906024
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com. Inclusion Criteria: Subjects with T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma refractory to or relapsed from standard therapies Life expectancy of at least 2 months Performance status (PS) 0-1 (a measure of the ability to carry out activities of daily living); subjects with PS 2 are eligible if due to disease related symptoms Prior anti-cancer treatment permitted (with specific criteria) Adequate organ function Exclusion Criteria: Infection Elevated triglycerides Gastro-intestinal disease with increased risk of diarrhea (e.g. inflammatory bowel disease) Unable to tolerate bone marrow biopsy Taking medications known to increase risk of Torsades De Pointes (an abnormal heart rhythm)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Escalation Phase: BMS-906024<br>BMS-906024 escalating doses starting at 0.3 mg solution for intravenous (IV) administration once weekly continuously until disease progression or unacceptable toxicity | Drug: BMS-906024<br> <br> * Other names: Notch inhibitor;|
| Experimental: Expansion Phase: BMS-906024 + Dexamethasone<br>BMS-906024 maximum tolerated dose (To be determined) solution for IV administration once weekly and Dexamethasone 20mg/day tablet by mouth (Oral) for 3-4 days every week for 3-4 weeks per cycle continuously until disease progression or unacceptable toxicity | Drug: BMS-906024<br> <br> * Other names: Notch inhibitor;Drug: Dexamethasone<br> <br> * Other names: Baycadron;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events as a measure of safety and tolerability |  | Weekly assessments until study discontinuation due to disease progression or unacceptable adverse events as well as an assessment 30 days after treatment discontinuation with an average time on study expected to be < 1 year. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease assessments in bone marrow & by computed tomography (CT)/ magnetic resonance imaging (MRI) |  | Disease assessments at least every 8 weeks during treatment | 
| Pharmacokinetics of BMS-906024 and its metabolite BMS-911557: maximum observed concentration (Cmax) |  | Pharmacokinetics at multiple time points during the first 4 weeks of dosing | 
| Pharmacokinetics of BMS-906024 and its metabolite BMS-911557: minimum observed concentration (Cmin) |  | Pharmacokinetics at multiple time points during the first 4 weeks of dosing | 
| Pharmacokinetics of BMS-906024 and its metabolite BMS-911557: area under the concentration-time curve (AUC) |  | Pharmacokinetics at multiple time points during the first 4 weeks of dosing | 
| Pharmacokinetics of BMS-906024 and its metabolite BMS-911557: time to reach maximum observed concentration (Tmax) |  | Pharmacokinetics at multiple time points during the first 4 weeks of dosing | 
| Pharmacokinetics of BMS-906024 and its metabolite BMS-911557: terminal phase elimination half-life (T-Half) |  | Pharmacokinetics at multiple time points during the first 4 weeks of dosing | 
| Pharmacokinetics of BMS-906024 and its metabolite BMS-911557: accumulation index (ratio of AUC at steady state to AUC after first dose) |  | Pharmacokinetics at multiple time points during the first 4 weeks of dosing | 
| Pharmacodynamics (percent change from baseline in mRNA expression of Notch pathway-related genes in blood cells) |  | Pharmacodynamic sampling: in blood during the first 8 weeks of dosing |