Study of the Glutaminase Inhibitor CB-839 in Hematological Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Calithera Biosciences, Inc
Sponsor:
Information provided by (Responsible Party):
Calithera Biosciences, Inc
ClinicalTrials.gov Identifier:
NCT02071888
First received: February 14, 2014
Last updated: October 15, 2014
Last verified: October 2014
  Purpose

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 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. In Part 2, all patients will receive the recommended Phase 2 dose. Both Parts 1 and 2 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.


Condition Intervention Phase
Non-Hodgkin's Lymphoma (NHL)
Multiple Myeloma
Waldenstrom's Macroglobulinemia (WM)
Diffuse Large B-cell Lymphoma (DLBCL),
Other B-cell NHL Subtypes, Including WM
T-cell NHL
Drug: CB-839
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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 Advanced and/or Treatment-Refractory Hematological Malignancies

Resource links provided by NLM:


Further study details as provided by Calithera Biosciences, Inc:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics: Area under the Curve (AUC) of CB-839 concentration in blood [ Time Frame: Study Days 1, 15, and 22 ] [ Designated as safety issue: No ]
  • Pharmacodynamics: % inhibition of glutaminase in blood [ Time Frame: Study Days 1 and 15 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 65
Study Start Date: February 2014
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CB-839
CB-839 is administered as oral capsules three times daily (TID) in 21-day cycles until disease progression or unacceptable toxicity
Drug: CB-839
Glutaminase inhibitor

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02071888

Contacts
Contact: Robin King (615) 329-7346 robin.king@scri-innovations.com
Contact: Sara Ramsey (615) 329-7240 sara.ramsey@scri-innovations.com

Locations
United States, Arizona
Mayo Clinic Recruiting
Scottsdale, Arizona, United States, 85259-5499
Contact: Clinical Trials Office - All Mayo Clinic Locations    507-538-7623      
Principal Investigator: Keith K Stewart, MB, ChB         
United States, Colorado
Colorado Blood Cancer Institute Recruiting
Denver, Colorado, United States, 80218
Principal Investigator: Jeffrey V Matuos, MD         
United States, New Jersey
John Theruer Cancer Center at Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
Principal Investigator: David S Siegel, MD, PhD         
United States, New York
Weill Cornell Medical College Recruiting
New York, New York, United States, 10065
Principal Investigator: Ruben Niesvizky, MD         
Memorial Sloan Kettering Cancer Center Recruiting
New York City, New York, United States, 10065
Principal Investigator: Anas Younes, MD         
United States, Pennsylvania
University of Pennsylvania, Abramson Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19104
Principal Investigator: Dan T Vogl, MD, MSCE         
United States, Tennessee
Tennessee Oncology, PLLC Recruiting
Nashville, Tennessee, United States, 37203
Principal Investigator: Jesus G Berdeja, MD         
Sponsors and Collaborators
Calithera Biosciences, Inc
Investigators
Study Director: Donald K Strickland, MD SCRI Innovations
  More Information

Additional Information:
No publications provided

Responsible Party: Calithera Biosciences, Inc
ClinicalTrials.gov Identifier: NCT02071888     History of Changes
Other Study ID Numbers: CX-839-002
Study First Received: February 14, 2014
Last Updated: October 15, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Calithera Biosciences, Inc:
Non-Hodgkin's lymphoma
Waldenstrom's macroglobulinemia
Multiple myeloma
glutaminase
glutamine

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Non-Hodgkin
Multiple Myeloma
Neoplasms, Plasma Cell
Waldenstrom Macroglobulinemia
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases

ClinicalTrials.gov processed this record on October 29, 2014