Study of the Glutaminase Inhibitor CB-839 in Leukemia

Acute Myeloid Leukemia (AML) Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02071927
• Other study ID #: CX-839-003
• Status: Completed
• Phase: Phase 1
• First received: February 14, 2014
• Last updated: February 7, 2017
• Start date: March 2014
• Est. completion date: December 2016

Study information

• Verified date: February 2017
• Source: Calithera Biosciences, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: December 2016
• Est. primary completion date: October 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Lymphocytic Leukemia (ALL)
• Acute Myeloid Leukemia (AML)
• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myeloid, Acute
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• CB-839
Single-agent CB-839
• CB-Aza
CB-839 in combination with standard dose azacitidine

Locations

Country	Name	City	State
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Northwestern University Feinberg School of Medicine	Chicago	Illinois
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Tennessee Oncology, PLLC	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Calithera Biosciences, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Pharmacokinetics: Area under the Curve (AUC) of CB-839 concentration in blood		Study Days 1, 15, and 22
Secondary	Pharmacodynamics: % inhibition of glutaminase in blood		Study Days 1 and 15
Secondary	Clinical Activity: % of Tumor Cells in Bone Marrow		Every 21 days from study start, assessed for an expected average of 6 months

External Links

•   Link