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NCT Number: NCT02071888

Study of the Glutaminase Inhibitor CB-839 in Hematological Tumors

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.

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Key information

Conditions

Non-Hodgkin's Lymphoma (NHL) Blood Protein Disorders Cardiovascular Diseases Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Immune System Diseases Immunoproliferative Disorders Lymphatic Diseases Lymphoma Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Multiple Myeloma Neoplasms Neoplasms by Histologic Type Neoplasms, Plasma Cell Other B-cell NHL Subtypes, Including WM Paraproteinemias T-cell NHL Vascular Diseases Waldenstrom Macroglobulinemia Waldenstrom's Macroglobulinemia (WM)

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Mayo Clinic, Scottsdale, Arizona, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

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

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

Treatment and study plan

CB-839

Drug

Glutaminase inhibitor

CB-839 and low dose dexamethasone

Drug

CB-839 and low dose dexamethasone

Other names: CBd

CB-839, pomalidomide, and low dose dexamethasone

Drug

CB-839, pomalidomide, and low dose dexamethasone

Other names: CBPd

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 for 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: 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

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 Advanced and/or Treatment-Refractory Hematological Malignancies

Important dates

Study start
2014
Primary completion
2016
Study completion
2016
First posted
Feb 26, 2014
Registry last updated
Jul 18, 2018

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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