Study of the Glutaminase Inhibitor CB-839 in Hematological Tumors

July 16, 2018 updated by: Calithera Biosciences, Inc

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

25

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85259-5499
        • Mayo Clinic
    • Colorado
      • Denver, Colorado, United States, 80218
        • Colorado Blood Cancer Institute
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Winship Cancer Institute of Emory School of Medicine
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • John Theruer Cancer Center at Hackensack University Medical Center
    • New York
      • New York, New York, United States, 10065
        • Weill Cornell Medical College
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania, Abramson Cancer Center
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology, PLLC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / 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:
  • CBd
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:
  • CBd
Drug: CB-839, pomalidomide, and low dose dexamethasone
CB-839, pomalidomide, and low dose dexamethasone
Other Names:
  • CBPd

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Safety and tolerability of CB-839: Incidence of adverse events
Time Frame: Every 21 days from study start until disease progression or unacceptable toxicity, assessed for an expected average of 6 months
Every 21 days from study start until disease progression or unacceptable toxicity, assessed for an expected average of 6 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Pharmacokinetics: Area under the Curve (AUC) of CB-839 concentration in blood
Time Frame: Study Days 1, 15, and 22
Study Days 1, 15, and 22
Pharmacodynamics: % inhibition of glutaminase in blood
Time Frame: Study Days 1 and 15
Study Days 1 and 15
Clinical activity: Change in tumor size from baseline
Time Frame: Every 9 weeks (NHL) or 3 weeks (MM and WM), assessed for an expected average of 6 months
Every 9 weeks (NHL) or 3 weeks (MM and WM), assessed for an expected average of 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Calithera Biosciences, Inc

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2014

Primary Completion (ACTUAL)

April 1, 2016

Study Completion (ACTUAL)

April 1, 2016

Study Registration Dates

First Submitted

February 14, 2014

First Submitted That Met QC Criteria

February 24, 2014

First Posted (ESTIMATE)

February 26, 2014

Study Record Updates

Last Update Posted (ACTUAL)

July 18, 2018

Last Update Submitted That Met QC Criteria

July 16, 2018

Last Verified

July 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CX-839-002

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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