Study of the Glutaminase Inhibitor CB-839 in Leukemia

Sponsor

Calithera Biosciences, Inc (Industry)

Overall Status

Completed

CT.gov ID

NCT02071927

Collaborator

(none)

Enrollment

Locations

Arms

33.1

Actual Duration (Months)

8.6

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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 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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia (AML) Acute Lymphocytic Leukemia (ALL)	Drug: CB-839 Drug: CB-Aza	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

43 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (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 Relapsed and/or Treatment-Refractory Leukemia

Actual Study Start Date :

Mar 1, 2014

Actual Primary Completion Date :

Oct 1, 2016

Actual Study Completion Date :

Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CB-839 CB-839 administered as oral capsules two (BID) or three times daily (TID) in 21-day cycles until disease progression or unacceptable toxicity	Drug: CB-839 Single-agent CB-839 Other Names: Glutaminase inhibitor
Experimental: CB-Aza CB-839 administered as oral capsules twice daily (BID) in combination with azacitidine in 28-day cycles until disease progression or unacceptable toxicity	Drug: CB-839 Single-agent CB-839 Other Names: Glutaminase inhibitor Drug: CB-Aza CB-839 in combination with standard dose azacitidine Other Names: combo CB-839 and azacitidine

Arm

Intervention/Treatment

Experimental: CB-839

CB-839 administered as oral capsules two (BID) or three times daily (TID) in 21-day cycles until disease progression or unacceptable toxicity

Drug: CB-839

Single-agent CB-839

Other Names:

Glutaminase inhibitor

Experimental: CB-Aza

CB-839 administered as oral capsules twice daily (BID) in combination with azacitidine in 28-day cycles until disease progression or unacceptable toxicity

Drug: CB-839

Single-agent CB-839

Other Names:

Glutaminase inhibitor

Drug: CB-Aza

CB-839 in combination with standard dose azacitidine

Other Names:

combo CB-839 and azacitidine

Outcome Measures

Primary Outcome Measures

Safety and tolerability of CB-839: Incidence of adverse events [Every 21 days from study start until disease progression or unacceptable toxicity, assessed an expected average of 6 months]

Secondary Outcome Measures

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: % of Tumor Cells in Bone Marrow [Every 21 days from study start, assessed for an expected average of 6 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Colorado Blood Cancer Institute	Denver	Colorado	United States	80218
2	Northwestern University Feinberg School of Medicine	Chicago	Illinois	United States	60611
3	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
4	Tennessee Oncology, PLLC	Nashville	Tennessee	United States	37203
5	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030