Study of the Glutaminase Inhibitor CB-839 in Hematological Tumors

Status:	Completed
Conditions:	Blood Cancer, Lymphoma, Lymphoma, Hematology, Hematology, Hematology
Therapuetic Areas:	Hematology, Oncology
Healthy:	No
Age Range:	18 - Any
Updated:	7/20/2018
Start Date:	February 2014
End Date:	April 2016

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

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.

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

We found this trial at

sites

Tennessee Oncology, PLLC

250 25th Ave N, Ste 100
Nashville, Tennessee 37023

615-320-5090