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

Phase 1

Completed

• Conditions: Precursor T-Cell Lymphoblastic Lymphoma; Lymphoblastic Leukemia, Acute T-cell
• Interventions: Drug: BMS-906024; Drug: Dexamethasone

• Registration Number: NCT01363817
• Lead Sponsor: Bristol-Myers Squibb

Brief Summary

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

Minimum Age: 10 years and older at selected sites

Study Timeline

• Study First Submitted: 2011-04-22
• Study First Submitted QC: 2011-05-31
• Study First Posted: 2011-06-02
• Study Start: 2011-09-28
• Primary Completion: 2018-02-07
• Study Completion: 2018-02-07
• Status Verified: 2019-07
• Last Update Submitted: 2019-07-29
• Last Update Posted: 2019-07-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 31

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

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Escalation Phase: BMS-906024	BMS-906024	BMS-906024 escalating doses starting at 0.3 mg solution for intravenous (IV) administration once weekly continuously until disease progression or unacceptable toxicity
Expansion Phase: BMS-906024 + Dexamethasone	BMS-906024	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
Expansion Phase: BMS-906024 + Dexamethasone	Dexamethasone	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

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (5)

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

The University Of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Local Institution; 🇫🇷 Paris Cedex 10, France

Johann Wolfgang Goethe Universitaet; 🇩🇪 Frankfurt/main, Germany