Brief Title
Study of the Glutaminase Inhibitor CB-839 in Hematological Tumors
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 Advanced and/or Treatment-Refractory Hematological Malignancies
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 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 two or 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 and will enroll patients with advanced and/or treatment-refractory Non-Hodgkin's
Lymphoma (NHL), Multiple Myeloma (MM), or Waldenström's macroglobulinemia (WM)
In Part 2, all patients will receive the recommended Phase 2 dose. This part 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.
As an extension of Part 2, a cohort of patients with relapsed and refractory MM will be
enrolled to receive low dose dexamethasone and CB-839. A second cohort of patients with
relapsed or refractory disease following at least 2 prior treatment regimens will be enrolled
to receive CB-839 in combination with standard-dose pomalidomide and low-dose dexamethasone
to further evaluate this triple combination.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Safety and tolerability of CB-839: Incidence of adverse events
Secondary Outcome
Pharmacokinetics: Area under the Curve (AUC) of CB-839 concentration in blood
Condition
Non-Hodgkin's Lymphoma (NHL)
Intervention
CB-839
Study Arms / Comparison Groups
CB-839
Description: CB-839 is administered as oral capsules three times daily (TID) or twice daily with food (BIDf) in 21-day cycles until disease progression or unacceptable toxicity
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
25
Start Date
February 2014
Completion Date
April 2016
Primary Completion Date
April 2016
Eligibility Criteria
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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Keith W Orford, MD, PhD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT02071888
Organization ID
CX-839-002
Responsible Party
Sponsor
Study Sponsor
Calithera Biosciences, Inc
Study Sponsor
Keith W Orford, MD, PhD, Study Director, Calithera Biosciences
Verification Date
July 2018