Study of the Glutaminase Inhibitor CB-839 in Hematological Tumors

NCT ID: NCT02071888

Last Updated: 2018-07-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-28
• Study Completion Date: 2016-04-30

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.

Conditions

Non-Hodgkin's Lymphoma (NHL); Multiple Myeloma; Waldenstrom's Macroglobulinemia (WM); Other B-cell NHL Subtypes, Including WM; T-cell NHL

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

CB-839

Intervention Type: DRUG

Glutaminase inhibitor

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

Group Type: EXPERIMENTAL

CB-839

Intervention Type: DRUG

Glutaminase inhibitor

CB-839 and low dose dexamethasone

Intervention Type: DRUG

CB-839 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

Group Type: EXPERIMENTAL

CB-839

Intervention Type: DRUG

Glutaminase inhibitor

CB-839 and low dose dexamethasone

Intervention Type: DRUG

CB-839 and low dose dexamethasone

CB-839, pomalidomide, and low dose dexamethasone

Intervention Type: DRUG

CB-839, pomalidomide, and low dose dexamethasone

Interventions

CB-839

Glutaminase inhibitor

Intervention Type: DRUG

CB-839 and low dose dexamethasone

CB-839 and low dose dexamethasone

Intervention Type: DRUG

CB-839, pomalidomide, and low dose dexamethasone

CB-839, pomalidomide, and low dose dexamethasone

Intervention Type: DRUG

Other Intervention Names

CBd; CBPd

Eligibility Criteria

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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Calithera Biosciences, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Keith W Orford, MD, PhD

Role: STUDY_DIRECTOR

Calithera Biosciences

Locations

Mayo Clinic

Scottsdale, Arizona, United States

Colorado Blood Cancer Institute

Denver, Colorado, United States

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

Weill Cornell Medical College

New York, New York, United States

University of Pennsylvania, Abramson Cancer Center

Philadelphia, Pennsylvania, United States

Tennessee Oncology, PLLC

Nashville, Tennessee, United States

Countries

United States

Other Identifiers

CX-839-002

Identifier Type: -

Identifier Source: org_study_id