A Phase 1 Study of the Safety, Pharmacokinetics, and Pharmacodynamics of Escalating Oral Doses of the Glutaminase Inhibitor CB-839 in Patients With Advanced and/or Treatment-Refractory Hematological Malignancies

Location:

Phoenix/Scottsdale, Ariz.

Trial status:

Open for Enrollment

Why is this study being done?

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 advanced hematologic malignancies. This study is an open-label Phase 1 evaluation of CB-839 in subjects with hematological tumors. Patients will receive CB-839 capsules orally three times daily. The study will be conducted in 2 parts. Part 1 is a dose escalation study to identify the recommended Phase 2 dose. In Part 2, all patients will receive the recommended Phase 2 dose. Both Parts 1 and 2 will enroll patients with advanced and/or treatment-refractory Non-Hodgkin's Lymphoma (NHL), Multiple Myeloma (MM), or Waldenström's macroglobulinemia (WM). 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.

Who is eligible to participate?

Disease-Specific Inclusion Criteria Patients must have one of the following diseases that is either relapsed or refractory to 2 or more prior treatments: - NHL: At least one measurable lesion - WM: Measurable IgM, with a minimum level of ≥ 2x ULN - MM: Serum M-protein ≥ 0.5 g/dL and/or urine M-protein ≥ 200 mg/24 hr. In Part 2, disease that is considered measurable per the IMWG criteria Other Inclusion Criteria - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 - Life Expectancy of at least 3 months - Adequate hepatic, renal, cardiac and hematological function Exclusion Criteria - Any other current malignancy - Treatment with an unapproved, investigational therapeutic agent, immunotherapy or biological therapy within 21 days prior to the first dose of study drug - Recent bone marrow transplant - Unable to receive medications by mouth - Major surgery within 28 days before the first dose of study drug - 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 the first dose of study drug - Refractory nausea and vomiting or other situation that may preclude adequate absorption - Other conditions that could interfere with treatment

Last updated:

6/20/2014

NCT ID:

NCT02071888

IRB Number:

14-000452