Study of the Glutaminase Inhibitor CB-839 in Hematological Tumors

Phase 1

Completed

• Conditions: Other B-cell NHL Subtypes, Including WM; T-cell NHL; Non-Hodgkin's Lymphoma (NHL); Multiple Myeloma; Waldenstrom's Macroglobulinemia (WM)
• Interventions: Drug: CB-839; Drug: CB-839 and low dose dexamethasone; Drug: CB-839, pomalidomide, and low dose dexamethasone

• Registration Number: NCT02071888
• Lead Sponsor: Calithera Biosciences, Inc

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-02
• Study First Submitted: 2014-02-14
• Study First Submitted QC: 2014-02-24
• Study First Posted: 2014-02-26
• Primary Completion: 2016-04
• Study Completion: 2016-04
• Status Verified: 2018-07
• Last Update Submitted: 2018-07-16
• Last Update Posted: 2018-07-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CB-839 and low dose dexamethasone	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
CB-839, pomalidomide, and low dose dexamethasone	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
CB-839, pomalidomide, and low dose dexamethasone	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 pomalidomide and dexamethasone until disease progression or unacceptable toxicity
CB-839	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
CB-839 and low dose dexamethasone	CB-839	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
CB-839, pomalidomide, and low dose dexamethasone	CB-839	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

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (7)

Winship Cancer Institute of Emory School of Medicine; 🇺🇸 Atlanta, Georgia, United States

John Theruer Cancer Center at Hackensack University Medical Center; 🇺🇸 Hackensack, New Jersey, United States

Mayo Clinic; 🇺🇸 Scottsdale, Arizona, United States

University of Pennsylvania, Abramson Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States

Weill Cornell Medical College; 🇺🇸 New York, New York, United States

Colorado Blood Cancer Institute; 🇺🇸 Denver, Colorado, United States

Tennessee Oncology, PLLC; 🇺🇸 Nashville, Tennessee, United States