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Study of the Glutaminase Inhibitor CB-839 in Leukemia

Phase 1
Completed
Conditions
Acute Myeloid Leukemia (AML)
Acute Lymphocytic Leukemia (ALL)
Interventions
Drug: CB-Aza
Registration Number
NCT02071927
Lead Sponsor
Calithera Biosciences, Inc
Brief Summary

Many tumor cells, in contrast to normal cells, have been shown to require the amino acid glutamine to produce energy for growth and survival. To exploit the dependence of tumors on glutamine, CB-839, a potent and selective inhibitor of the first enzyme in glutamine utilization, glutaminase, will be tested in this Phase 1 study in patients with leukemia.

This study is an open-label Phase 1 evaluation of CB-839 in subjects with leukemia. Part 1 is a dose escalation study to identify the recommended Phase 2 dose as a single agent and in combination with azacitidine. Patients enrolled into Part 2 will be treated with the recommended Phase 2 dose. As an extension of Part 2, patients with relapsed/ refractory or newly diagnosed AML will be treated with CB-839 in combination with azacitidine.

All patients will be assessed for safety, pharmacokinetics (plasma concentration of drug), pharmacodynamics (inhibition of glutaminase), biomarkers (biochemical markers that may predict responsiveness in later studies), and tumor response.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
43
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
CB-839CB-839CB-839 administered as oral capsules two (BID) or three times daily (TID) in 21-day cycles until disease progression or unacceptable toxicity
CB-AzaCB-839CB-839 administered as oral capsules twice daily (BID) in combination with azacitidine in 28-day cycles until disease progression or unacceptable toxicity
CB-AzaCB-AzaCB-839 administered as oral capsules twice daily (BID) in combination with azacitidine in 28-day cycles until disease progression or unacceptable toxicity
Primary Outcome Measures
NameTimeMethod
Safety and tolerability of CB-839: Incidence of adverse eventsEvery 21 days from study start until disease progression or unacceptable toxicity, assessed an expected average of 6 months
Secondary Outcome Measures
NameTimeMethod
Pharmacodynamics: % inhibition of glutaminase in bloodStudy Days 1 and 15
Pharmacokinetics: Area under the Curve (AUC) of CB-839 concentration in bloodStudy Days 1, 15, and 22
Clinical Activity: % of Tumor Cells in Bone MarrowEvery 21 days from study start, assessed for an expected average of 6 months

Trial Locations

Locations (5)

Colorado Blood Cancer Institute

🇺🇸

Denver, Colorado, United States

Northwestern University Feinberg School of Medicine

🇺🇸

Chicago, Illinois, United States

Roswell Park Cancer Institute

🇺🇸

Buffalo, New York, United States

Tennessee Oncology, PLLC

🇺🇸

Nashville, Tennessee, United States

University of Texas MD Anderson Cancer Center

🇺🇸

Houston, Texas, United States

Colorado Blood Cancer Institute
🇺🇸Denver, Colorado, United States

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