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NCT Number: NCT02071927

Study of the Glutaminase Inhibitor CB-839 in 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.

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Key information

Conditions

Acute Myeloid Leukemia (AML) Acute Lymphocytic Leukemia (ALL) Hematologic Diseases Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Leukemia Leukemia, Lymphoid Leukemia, Myeloid Leukemia, Myeloid, Acute Lymphatic Diseases Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Precursor Cell Lymphoblastic Leukemia-Lymphoma

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Colorado Blood Cancer Institute, Denver, Colorado, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

CB-839

Drug

Single-agent CB-839

Other names: Glutaminase inhibitor

CB-Aza

Drug

CB-839 in combination with standard dose azacitidine

Other names: combo CB-839 and azacitidine

Primary outcomes

  1. 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 outcomes

  1. Pharmacokinetics: Area under the Curve (AUC) of CB-839 concentration in blood

    Time frame: Study Days 1, 15, and 22

  2. Pharmacodynamics: % inhibition of glutaminase in blood

    Time frame: Study Days 1 and 15

  3. Clinical Activity: % of Tumor Cells in Bone Marrow

    Time frame: Every 21 days from study start, assessed for an expected average of 6 months

Sponsors and collaborators

Lead sponsor

Calithera Biosciences, Inc

Industry

Registry information

Official study 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

Important dates

Study start
2014
Primary completion
2016
Study completion
2016
First posted
Feb 26, 2014
Registry last updated
Feb 9, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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