Study of the Glutaminase Inhibitor CB-839 in Hematological Tumors
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: CB-839 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 |
Drug: CB-839
Glutaminase inhibitor
|
| Experimental: CB-839 and low dose dexamethasone CB-839 is administered as oral capsules twice daily with food (BIDf) in 28 day cycles in combination with dexamethasone until disease progression or unacceptable toxicity |
Drug: CB-839
Glutaminase inhibitor
Drug: CB-839 and low dose dexamethasone
CB-839 and low dose dexamethasone
Other Names:
|
| Experimental: CB-839, pomalidomide, and low dose dexamethasone CB-839 is administered as oral capsules twice daily with food (BIDf) in 28 day cycles in combination with pomalidomide and dexamethasone until disease progression or unacceptable toxicity |
Drug: CB-839
Glutaminase inhibitor
Drug: CB-839 and low dose dexamethasone
CB-839 and low dose dexamethasone
Other Names:
Drug: CB-839, pomalidomide, and low dose dexamethasone
CB-839, pomalidomide, and low dose dexamethasone
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Safety and tolerability of CB-839: Incidence of adverse events [Every 21 days from study start until disease progression or unacceptable toxicity, assessed for an expected average of 6 months]
Secondary Outcome Measures
- Pharmacokinetics: Area under the Curve (AUC) of CB-839 concentration in blood [Study Days 1, 15, and 22]
- Pharmacodynamics: % inhibition of glutaminase in blood [Study Days 1 and 15]
- Clinical activity: Change in tumor size from baseline [Every 9 weeks (NHL) or 3 weeks (MM and WM), assessed for an expected average of 6 months]
Eligibility Criteria
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
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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
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Life Expectancy of at least 3 months
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Adequate hepatic, renal, cardiac and hematological function
Exclusion Criteria
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Any other current malignancy
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Treatment with an unapproved, investigational therapeutic agent, immunotherapy or biological therapy within 21 days prior to the first dose of study drug
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Recent bone marrow transplant
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Unable to receive medications by mouth
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Major surgery within 28 days before the first dose of study drug
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Uncontrolled, active infection; patients who are known to have HIV infection/ seropositivity, Hepatitis A, B, or C, or CMV reactivation
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Significant neurotoxicity/neuropathy (Grade 3 or higher) within 14 days prior to the first dose of study drug
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Refractory nausea and vomiting or other situation that may preclude adequate absorption
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Other conditions that could interfere with treatment
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mayo Clinic | Scottsdale | Arizona | United States | 85259-5499 |
| 2 | Colorado Blood Cancer Institute | Denver | Colorado | United States | 80218 |
| 3 | Winship Cancer Institute of Emory School of Medicine | Atlanta | Georgia | United States | 30322 |
| 4 | John Theruer Cancer Center at Hackensack University Medical Center | Hackensack | New Jersey | United States | 07601 |
| 5 | Weill Cornell Medical College | New York | New York | United States | 10065 |
| 6 | University of Pennsylvania, Abramson Cancer Center | Philadelphia | Pennsylvania | United States | 19104 |
| 7 | Tennessee Oncology, PLLC | Nashville | Tennessee | United States | 37203 |
Sponsors and Collaborators
- Calithera Biosciences, Inc
Investigators
- Study Director: Keith W Orford, MD, PhD, Calithera Biosciences
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- CX-839-002