Study of the Glutaminase Inhibitor CB-839 in Leukemia
A Phase 1 Study of the Safety, Pharmacokinetics, and Pharmacodynamics of Escalating Oral Doses of the Glutaminase Inhibitor CB-839 in Patients With Relapsed and/or Treatment-Refractory Leukemia
1 other identifier
interventional
43
1 country
5
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Mar 2014
Typical duration for phase_1
5 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 14, 2014
CompletedFirst Posted
Study publicly available on registry
February 26, 2014
CompletedStudy Start
First participant enrolled
March 1, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2016
CompletedFebruary 9, 2017
February 1, 2017
2.6 years
February 14, 2014
February 7, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Safety and tolerability of CB-839: Incidence of adverse events
Every 21 days from study start until disease progression or unacceptable toxicity, assessed an expected average of 6 months
Secondary Outcomes (3)
Pharmacokinetics: Area under the Curve (AUC) of CB-839 concentration in blood
Study Days 1, 15, and 22
Pharmacodynamics: % inhibition of glutaminase in blood
Study Days 1 and 15
Clinical Activity: % of Tumor Cells in Bone Marrow
Every 21 days from study start, assessed for an expected average of 6 months
Study Arms (2)
CB-839
EXPERIMENTALCB-839 administered as oral capsules two (BID) or three times daily (TID) in 21-day cycles until disease progression or unacceptable toxicity
CB-Aza
EXPERIMENTALCB-839 administered as oral capsules twice daily (BID) in combination with azacitidine in 28-day cycles until disease progression or unacceptable toxicity
Interventions
Eligibility Criteria
You may qualify if:
- Diagnosis of AML or ALL, relapsed or refractory after at least 1 prior treatment regimen. Newly-diagnosed patients ≥ 60 years old who have refused or are considered unfit for standard chemotherapy regimens or stem cell transplantation are also eligible.
- Patients must have no available approved therapies that confer clinical benefit
- All patients must have bone marrow involvement of their tumor, with documented blast percentage of \> 5%.
- Peripheral blood blast count must be ≤ 30,000 cells/µL.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
- Adequate hepatic, renal, and cardiac function
You may not qualify if:
- Any other current malignancy
- Patients with acute promyelocytic leukemia (APL)
- Treatment with an unapproved, investigational agent within 21 days of the first dose of study drug
- Allogeneic hematopoietic stem cell transplant or Donor Lymphocyte Infusion within 90 days prior to to the first dose of study drug
- Active GVHD
- Unable to receive medications by mouth
- Major surgery within 28 days before Cycle 1 Day 1
- Uncontrolled, active infection; patients who are known to have HIV infection/ seropositivity, Hepatitis A, B, or C, or CMV reactivation
- Significant neurotoxicity/neuropathy (Grade 3 or higher) within 14 days prior to Day 1
- Refractory nausea and vomiting or other situation that may preclude adequate absorption
- Conditions that could interfere with treatment and procedures
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (5)
Colorado Blood Cancer Institute
Denver, Colorado, 80218, United States
Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Tennessee Oncology, PLLC
Nashville, Tennessee, 37203, United States
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Related Publications (1)
Aden D, Sureka N, Zaheer S, Chaurasia JK, Zaheer S. Metabolic Reprogramming in Cancer: Implications for Immunosuppressive Microenvironment. Immunology. 2025 Jan;174(1):30-72. doi: 10.1111/imm.13871. Epub 2024 Oct 27.
PMID: 39462179DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Keith W Orford, MD, PhD
Calithera Biosciences
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 14, 2014
First Posted
February 26, 2014
Study Start
March 1, 2014
Primary Completion
October 1, 2016
Study Completion
December 1, 2016
Last Updated
February 9, 2017
Record last verified: 2017-02