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 - Full Text View

Purpose

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

Condition	Intervention	Phase
Lymphoblastic Leukemia, Acute T-cell Precursor T-Cell Lymphoblastic Lymphoma	Drug: BMS-906024 Drug: Dexamethasone	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Chronic Lymphocytic Leukemia Leukemia Lymphoma

Drug Information available for: Dexamethasone Dexamethasone acetate Dexamethasone sodium phosphate

U.S. FDA Resources

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:

Number of subjects with adverse events as a measure of safety and tolerability [ Time Frame: 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. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Disease assessments in bone marrow & by computed tomography (CT)/ magnetic resonance imaging (MRI) [ Time Frame: Disease assessments at least every 8 weeks during treatment ] [ Designated as safety issue: No ]
Pharmacokinetics of BMS-906024 and its metabolite BMS-911557: maximum observed concentration (Cmax) [ Time Frame: Pharmacokinetics at multiple time points during the first 4 weeks of dosing ] [ Designated as safety issue: No ]
Pharmacokinetics of BMS-906024 and its metabolite BMS-911557: minimum observed concentration (Cmin) [ Time Frame: Pharmacokinetics at multiple time points during the first 4 weeks of dosing ] [ Designated as safety issue: No ]
Pharmacokinetics of BMS-906024 and its metabolite BMS-911557: area under the concentration-time curve (AUC) [ Time Frame: Pharmacokinetics at multiple time points during the first 4 weeks of dosing ] [ Designated as safety issue: No ]
Pharmacokinetics of BMS-906024 and its metabolite BMS-911557: time to reach maximum observed concentration (Tmax) [ Time Frame: Pharmacokinetics at multiple time points during the first 4 weeks of dosing ] [ Designated as safety issue: No ]
Pharmacokinetics of BMS-906024 and its metabolite BMS-911557: terminal phase elimination half-life (T-Half) [ Time Frame: Pharmacokinetics at multiple time points during the first 4 weeks of dosing ] [ Designated as safety issue: No ]
Pharmacokinetics of BMS-906024 and its metabolite BMS-911557: accumulation index (ratio of AUC at steady state to AUC after first dose) [ Time Frame: Pharmacokinetics at multiple time points during the first 4 weeks of dosing ] [ Designated as safety issue: No ]
Pharmacodynamics (percent change from baseline in mRNA expression of Notch pathway-related genes in blood cells) [ Time Frame: Pharmacodynamic sampling: in blood during the first 8 weeks of dosing ] [ Designated as safety issue: No ]

Estimated Enrollment:	42
Study Start Date:	September 2011
Estimated Study Completion Date:	April 2014
Estimated Primary Completion Date:	April 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Escalation Phase: 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	Drug: BMS-906024 Other Name: Notch inhibitor
Experimental: Expansion Phase: BMS-906024 + 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	Drug: BMS-906024 Other Name: Notch inhibitor Drug: Dexamethasone Other Name: Baycadron

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01363817

Contacts

Contact: For participation information at a USA site use a phone number below. For site information outside the USA please email:		Clinical.Trials@bms.com
Contact: First line of email MUST contain NCT# & Site#. Only trial sites that are recruiting have contact information at this time.

Locations

United States, Massachusetts
Dana Farber Cancer Institute	Recruiting
Boston, Massachusetts, United States, 02215
Contact: Daniel Deangelo, Site 002 617-632-5918
United States, New York
Memorial Sloan Kettering Cancer Center	Recruiting
New York, New York, United States, 10065
Contact: Dan Douer, Site 003 212-639-2471
United States, Texas
The University Of Texas Md Anderson Cancer Center	Recruiting
Houston, Texas, United States, 77030
Contact: Patrick Zweidler-Mckay, Site 001 713-792-5683
France
Local Institution	Recruiting
Marseille Cedex 9, France, 13273
Contact: Site 005
Local Institution	Recruiting
Paris Cedex 10, France, 75475
Contact: Site 004
Germany
Local Institution	Recruiting
Frankfurt/Main, Germany, 60590
Contact: Site 006

Sponsors and Collaborators

Bristol-Myers Squibb

Investigators

Study Director:

Bristol-Myers Squibb

More Information

Additional Information:

BMS Clinical Trial Information This link exits the ClinicalTrials.gov site

BMS clinical trial educational resource This link exits the ClinicalTrials.gov site

Investigator Inquiry form This link exits the ClinicalTrials.gov site

For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT01363817 History of Changes
Other Study ID Numbers:	CA216-002, 2010-022727-29
Study First Received:	April 22, 2011
Last Updated:	March 28, 2013
Health Authority:	United States: Food and Drug Administration Germany: Federal Institute for Drugs and Medical Devices France: Ministry of Health

Additional relevant MeSH terms:

Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphoma
Lymphoma, Non-Hodgkin
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate

BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on June 18, 2013