Clinical trial NCT01363817: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lymphoblastic Leukemia, Acute T-cell
Precursor T-Cell Lymphoblastic Lymphoma
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2011-06-02
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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)

Primary outcomes:
measure: Number of subjects with adverse events as a measure of safety and tolerability
timeFrame: 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 outcomes:
measure: Disease assessments in bone marrow & by computed tomography (CT)/ magnetic resonance imaging (MRI)
timeFrame: Disease assessments at least every 8 weeks during treatment
measure: Pharmacokinetics of BMS-906024 and its metabolite BMS-911557: maximum observed concentration (Cmax)
timeFrame: Pharmacokinetics at multiple time points during the first 4 weeks of dosing
measure: Pharmacokinetics of BMS-906024 and its metabolite BMS-911557: minimum observed concentration (Cmin)
timeFrame: Pharmacokinetics at multiple time points during the first 4 weeks of dosing
measure: Pharmacokinetics of BMS-906024 and its metabolite BMS-911557: area under the concentration-time curve (AUC)
timeFrame: Pharmacokinetics at multiple time points during the first 4 weeks of dosing
measure: Pharmacokinetics of BMS-906024 and its metabolite BMS-911557: time to reach maximum observed concentration (Tmax)
timeFrame: Pharmacokinetics at multiple time points during the first 4 weeks of dosing
measure: Pharmacokinetics of BMS-906024 and its metabolite BMS-911557: terminal phase elimination half-life (T-Half)
timeFrame: Pharmacokinetics at multiple time points during the first 4 weeks of dosing
measure: Pharmacokinetics of BMS-906024 and its metabolite BMS-911557: accumulation index (ratio of AUC at steady state to AUC after first dose)
timeFrame: Pharmacokinetics at multiple time points during the first 4 weeks of dosing
measure: Pharmacodynamics (percent change from baseline in mRNA expression of Notch pathway-related genes in blood cells)
timeFrame: Pharmacodynamic sampling: in blood during the first 8 weeks of dosing
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Houston
country: United States
facility: The University Of Texas MD Anderson Cancer Center
state: Texas
city: Marseille Cedex 9
country: France
facility: Local Institution
city: Paris Cedex 10
country: France
facility: Local Institution
city: Frankfurt/main
country: Germany
facility: Johann Wolfgang Goethe Universitaet
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: