Study of the Glutaminase Inhibitor CB-839 in Leukemia

February 7, 2017 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 Relapsed and/or Treatment-Refractory Leukemia

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 leukemia.

This study is an open-label Phase 1 evaluation of CB-839 in subjects with leukemia. Part 1 is a dose escalation study to identify the recommended Phase 2 dose as a single agent and in combination with azacitidine. Patients enrolled into Part 2 will be treated with the recommended Phase 2 dose. As an extension of Part 2, patients with relapsed/ refractory or newly diagnosed AML will be treated with CB-839 in combination with azacitidine.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

43

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
    • Colorado
      • Denver, Colorado, United States, 80218
        • Colorado Blood Cancer Institute
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University Feinberg School of Medicine
    • New York
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology, PLLC
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas MD Anderson Cancer Center

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

Inclusion Criteria

  • Diagnosis of AML or ALL, relapsed or refractory after at least 1 prior treatment regimen. Newly-diagnosed patients ≥ 60 years old who have refused or are considered unfit for standard chemotherapy regimens or stem cell transplantation are also eligible.
  • Patients must have no available approved therapies that confer clinical benefit
  • All patients must have bone marrow involvement of their tumor, with documented blast percentage of > 5%.
  • Peripheral blood blast count must be ≤ 30,000 cells/µL.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
  • Adequate hepatic, renal, and cardiac function

Exclusion Criteria

  • Any other current malignancy
  • Patients with acute promyelocytic leukemia (APL)
  • Treatment with an unapproved, investigational agent within 21 days of the first dose of study drug
  • Allogeneic hematopoietic stem cell transplant or Donor Lymphocyte Infusion within 90 days prior to to the first dose of study drug
  • Active GVHD
  • Unable to receive medications by mouth
  • Major surgery within 28 days before Cycle 1 Day 1
  • 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 Day 1
  • Refractory nausea and vomiting or other situation that may preclude adequate absorption
  • Conditions that could interfere with treatment and procedures

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 Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CB-839
CB-839 administered as oral capsules two (BID) or three times daily (TID) in 21-day cycles until disease progression or unacceptable toxicity
Drug: CB-839
Single-agent CB-839
Other Names:
  • Glutaminase inhibitor
Experimental: CB-Aza
CB-839 administered as oral capsules twice daily (BID) in combination with azacitidine in 28-day cycles until disease progression or unacceptable toxicity
Drug: CB-839
Single-agent CB-839
Other Names:
  • Glutaminase inhibitor
Drug: CB-Aza
CB-839 in combination with standard dose azacitidine
Other Names:
  • combo CB-839 and azacitidine

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 an expected average of 6 months
Every 21 days from study start until disease progression or unacceptable toxicity, assessed 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: % of Tumor Cells in Bone Marrow
Time Frame: Every 21 days from study start, assessed for an expected average of 6 months
Every 21 days from study start, 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 (Actual)

March 1, 2014

Primary Completion (Actual)

October 1, 2016

Study Completion (Actual)

December 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 (Estimate)

February 9, 2017

Last Update Submitted That Met QC Criteria

February 7, 2017

Last Verified

February 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CX-839-003

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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