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.
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.
Brief Title
Study of the Glutaminase Inhibitor CB-839 in Leukemia
Categories
Completion Date
Completion Date Type
Actual
Conditions
Acute Myeloid Leukemia (AML)
Acute Lymphocytic Leukemia (ALL)
Eligibility Criteria
Inclusion Criteria
* 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
Exclusion Criteria
* 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
* 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
Exclusion Criteria
* 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
Inclusion Criteria
Inclusion Criteria
* 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
* 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
Gender
All
Gender Based
false
Keywords
leukemia
glutaminase
glutamine
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Estimated
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02071927
Org Class
Industry
Org Full Name
Calithera Biosciences, Inc
Org Study Id
CX-839-003
Overall Status
Completed
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
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
Primary Outcomes
Outcome Measure
Safety and tolerability of CB-839: Incidence of adverse events
Outcome Time Frame
Every 21 days from study start until disease progression or unacceptable toxicity, assessed an expected average of 6 months
Secondary Outcomes
Outcome Time Frame
Study Days 1, 15, and 22
Outcome Measure
Pharmacokinetics: Area under the Curve (AUC) of CB-839 concentration in blood
Outcome Time Frame
Study Days 1 and 15
Outcome Measure
Pharmacodynamics: % inhibition of glutaminase in blood
Outcome Time Frame
Every 21 days from study start, assessed for an expected average of 6 months
Outcome Measure
Clinical Activity: % of Tumor Cells in Bone Marrow
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Amit Verma
Investigator Email
amit.verma@einsteinmed.org
Investigator Phone
718-405-8505 / 718-904-2900