Study of the Glutaminase Inhibitor CB-839 in Hematological Tumors

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02071888
• Other study ID #: CX-839-002
• Status: Completed
• Phase: Phase 1
• Start date: February 2014
• Est. completion date: April 2016

Study information

• Verified date: July 2018
• Source: Calithera Biosciences, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• CB-839
Glutaminase inhibitor
• CB-839 and low dose dexamethasone
CB-839 and low dose dexamethasone
• CB-839, pomalidomide, and low dose dexamethasone
CB-839, pomalidomide, and low dose dexamethasone

Locations

Country	Name	City	State
United States	Winship Cancer Institute of Emory School of Medicine	Atlanta	Georgia
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	John Theruer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Weill Cornell Medical College	New York	New York
United States	University of Pennsylvania, Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Mayo Clinic	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Calithera Biosciences, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Pharmacokinetics: Area under the Curve (AUC) of CB-839 concentration in blood		Study Days 1, 15, and 22
Secondary	Pharmacodynamics: % inhibition of glutaminase in blood		Study Days 1 and 15
Secondary	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

External Links

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