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Study of the Glutaminase Inhibitor CB-839 in Hematological Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Calithera Biosciences, Inc
ClinicalTrials.gov Identifier:
NCT02071888
First received: February 14, 2014
Last updated: April 29, 2016
Last verified: April 2016
  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 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.


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
Drug: CB-839 and low dose dexamethasone
Drug: CB-839, pomalidomide, and low dose dexamethasone
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
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 ]

Enrollment: 25
Study Start Date: February 2014
Study Completion Date: April 2016
Primary Completion Date: April 2016 (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) or twice daily with food (BIDf) in 21-day cycles until disease progression or unacceptable toxicity
Drug: CB-839
Glutaminase inhibitor
Experimental: CB-839 and low dose dexamethasone
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
Glutaminase inhibitor
Drug: CB-839 and low dose dexamethasone
CB-839 and low dose dexamethasone
Other Name: CBd
Experimental: CB-839, pomalidomide, and low dose dexamethasone
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
Glutaminase inhibitor
Drug: CB-839 and low dose dexamethasone
CB-839 and low dose dexamethasone
Other Name: CBd
Drug: CB-839, pomalidomide, and low dose dexamethasone
CB-839, pomalidomide, and low dose dexamethasone
Other Name: CBPd

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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

Locations
United States, Arizona
Mayo Clinic
Scottsdale, Arizona, United States, 85259-5499
United States, Colorado
Colorado Blood Cancer Institute
Denver, Colorado, United States, 80218
United States, Georgia
Winship Cancer Institute of Emory School of Medicine
Atlanta, Georgia, United States, 30322
United States, New Jersey
John Theruer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New York
Weill Cornell Medical College
New York, New York, United States, 10065
United States, Pennsylvania
University of Pennsylvania, Abramson Cancer Center
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Tennessee Oncology, PLLC
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Calithera Biosciences, Inc
Investigators
Study Director: Keith W Orford, MD, PhD Calithera Biosciences
  More Information

Additional Information:
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: April 29, 2016
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
Multiple Myeloma
Neoplasms, Plasma Cell
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Waldenstrom Macroglobulinemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Pomalidomide
Thalidomide
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on December 02, 2016