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Study of the Glutaminase Inhibitor CB-839 in Leukemia

Primary Purpose

Acute Myeloid Leukemia (AML), Acute Lymphocytic Leukemia (ALL)

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CB-839
CB-Aza
Sponsored by
Calithera Biosciences, Inc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia (AML) focused on measuring leukemia, glutaminase, glutamine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Colorado Blood Cancer Institute
  • Northwestern University Feinberg School of Medicine
  • Roswell Park Cancer Institute
  • Tennessee Oncology, PLLC
  • University of Texas MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

CB-839

CB-Aza

Arm Description

CB-839 administered as oral capsules two (BID) or three times daily (TID) in 21-day cycles until disease progression or unacceptable toxicity

CB-839 administered as oral capsules twice daily (BID) in combination with azacitidine in 28-day cycles until disease progression or unacceptable toxicity

Outcomes

Primary Outcome Measures

Safety and tolerability of CB-839: Incidence of adverse events

Secondary Outcome Measures

Pharmacokinetics: Area under the Curve (AUC) of CB-839 concentration in blood
Pharmacodynamics: % inhibition of glutaminase in blood
Clinical Activity: % of Tumor Cells in Bone Marrow

Full Information

First Posted
February 14, 2014
Last Updated
February 7, 2017
Sponsor
Calithera Biosciences, Inc
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1. Study Identification

Unique Protocol Identification Number
NCT02071927
Brief Title
Study of the Glutaminase Inhibitor CB-839 in Leukemia
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 Relapsed and/or Treatment-Refractory Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
March 2014 (Actual)
Primary Completion Date
October 2016 (Actual)
Study Completion Date
December 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Calithera Biosciences, Inc

4. Oversight

Data Monitoring Committee
No

5. Study Description

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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia (AML), Acute Lymphocytic Leukemia (ALL)
Keywords
leukemia, glutaminase, glutamine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
43 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CB-839
Arm Type
Experimental
Arm Description
CB-839 administered as oral capsules two (BID) or three times daily (TID) in 21-day cycles until disease progression or unacceptable toxicity
Arm Title
CB-Aza
Arm Type
Experimental
Arm Description
CB-839 administered as oral capsules twice daily (BID) in combination with azacitidine in 28-day cycles until disease progression or unacceptable toxicity
Intervention Type
Drug
Intervention Name(s)
CB-839
Other Intervention Name(s)
Glutaminase inhibitor
Intervention Description
Single-agent CB-839
Intervention Type
Drug
Intervention Name(s)
CB-Aza
Other Intervention Name(s)
combo CB-839 and azacitidine
Intervention Description
CB-839 in combination with standard dose azacitidine
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
Pharmacokinetics: Area under the Curve (AUC) of CB-839 concentration in blood
Time Frame
Study Days 1, 15, and 22
Title
Pharmacodynamics: % inhibition of glutaminase in blood
Time Frame
Study Days 1 and 15
Title
Clinical Activity: % of Tumor Cells in Bone Marrow
Time Frame
Every 21 days from study start, assessed for an expected average of 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Keith W Orford, MD, PhD
Organizational Affiliation
Calithera Biosciences
Official's Role
Study Director
Facility Information:
Facility Name
Colorado Blood Cancer Institute
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Northwestern University Feinberg School of Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
Tennessee Oncology, PLLC
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.calithera.com
Description
Related Info

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Study of the Glutaminase Inhibitor CB-839 in Leukemia

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