Study of the Glutaminase Inhibitor CB-839 in Hematological Tumors

NCT02071888 | Completed Phase 1

• 1 other identifier: CX-839-002
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 7

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 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.

Conditions

Non-Hodgkin's Lymphoma (NHL); Multiple Myeloma; Waldenstrom's Macroglobulinemia (WM); Other B-cell NHL Subtypes, Including WM; T-cell NHL

Keywords

Non-Hodgkin's lymphoma; Waldenstrom's macroglobulinemia; Multiple myeloma; glutaminase; glutamine

Outcome Measures

Primary Outcomes (1)

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

  Every 21 days from study start until disease progression or unacceptable toxicity, assessed for an expected average of 6 months

Secondary Outcomes (3)

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

  Study Days 1, 15, and 22

• Pharmacodynamics: % inhibition of glutaminase in blood

  Study Days 1 and 15

• Clinical activity: Change in tumor size from baseline

  Every 9 weeks (NHL) or 3 weeks (MM and WM), assessed for an expected average of 6 months

Study Arms (3)

CB-839

EXPERIMENTAL

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

CB-839 and low dose dexamethasone

EXPERIMENTAL

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; Drug: CB-839 and low dose dexamethasone

CB-839, pomalidomide, and low dose dexamethasone

EXPERIMENTAL

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; Drug: CB-839 and low dose dexamethasone; Drug: CB-839, pomalidomide, and low dose dexamethasone

Interventions

CB-839 DRUG

Glutaminase inhibitor

CB-839; CB-839 and low dose dexamethasone; CB-839, pomalidomide, and low dose dexamethasone

CB-839 and low dose dexamethasone DRUG

CB-839 and low dose dexamethasone

Also known as: CBd

CB-839 and low dose dexamethasone; CB-839, pomalidomide, and low dose dexamethasone

CB-839, pomalidomide, and low dose dexamethasone DRUG

CB-839, pomalidomide, and low dose dexamethasone

Also known as: CBPd

CB-839, pomalidomide, and low dose dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
• Life Expectancy of at least 3 months
• Adequate hepatic, renal, cardiac and hematological function

You may not qualify if:

• 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

Sponsors & Collaborators

• Calithera Biosciences, Inc: lead

Study Sites (7)

Mayo Clinic

Scottsdale, Arizona, 85259-5499, United States

Location

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Winship Cancer Institute of Emory School of Medicine

Atlanta, Georgia, 30322, United States

Location

John Theruer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

University of Pennsylvania, Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Multiple Myeloma; Waldenstrom Macroglobulinemia

Interventions

CB-839; Dexamethasone; pomalidomide

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Keith W Orford, MD, PhD

  Calithera Biosciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2014
• First Posted: February 26, 2014
• Study Start: February 1, 2014
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: July 18, 2018

Record last verified: 2018-07

Locations

US (7)