Non-Hodgkin's Lymphoma (NHL)Phase 1NCT02071888
Study of the Glutaminase Inhibitor CB-839 in Hematological Tumors
A Phase 1 study testing CB-839, CB-839 and low dose dexamethasone and CB-839, pomalidomide, and low dose dexamethasone in people with Non-Hodgkin's Lymphoma (NHL) and Multiple Myeloma, run by Calithera Biosciences, Inc at 7 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Hodgkin's Lymphoma (NHL), Multiple Myeloma, Waldenstrom's Macroglobulinemia (WM)
- What is being tested?
- CB-839, CB-839 and low dose dexamethasone and CB-839, pomalidomide, and low dose dexamethasone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 7 sitesUnited States
- Study dates
- Feb 2014to Apr 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Winship Cancer Institute of Emory School of Medicine
Atlanta, Georgia, 30322
Colorado Blood Cancer Institute
Denver, Colorado, 80218
John Theruer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, 07601
Tennessee Oncology, PLLC
Nashville, Tennessee, 37203
Weill Cornell Medical College
New York, New York, 10065
University of Pennsylvania, Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
Mayo Clinic
Scottsdale, Arizona, 85259-5499
About this study
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
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)
Read more
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
- Being tested
- CB-839, CB-839 and low dose dexamethasone, CB-839, pomalidomide, and low dose dexamethasone
- Keywords
- Non-Hodgkin's lymphoma, Waldenstrom's macroglobulinemia, Multiple myeloma, glutaminase, glutamine
- Medical subject headings
- Lymphoma, Non-Hodgkin, Multiple Myeloma, Waldenstrom Macroglobulinemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CB-839Drug
Glutaminase inhibitor
CB-839 and low dose dexamethasoneDrug
Also called CBd
CB-839 and low dose dexamethasone
CB-839, pomalidomide, and low dose dexamethasoneDrug
Also called CBPd
CB-839, pomalidomide, and low dose dexamethasone
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: Drug: CB-839; Drug: CB-839 and low dose dexamethasone; Drug: CB-839, pomalidomide, and low dose dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of CB-839: Incidence of adverse events
Measured: 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
Measured: Study Days 1, 15, and 22
Pharmacodynamics: % inhibition of glutaminase in blood
Measured: Study Days 1 and 15
Clinical activity: Change in tumor size from baseline
Measured: Every 9 weeks (NHL) or 3 weeks (MM and WM), assessed for an expected average of 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2014 (estimated)
- Study startFeb 2014
- Primary completionApr 2016
- Study completionApr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Hodgkin's Lymphoma (NHL)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Calithera Biosciences, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Keith W Orford, MD, PhD, Study director, Calithera Biosciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02071888
- Sponsor's protocol ID
- CX-839-002
- Status last verified
- Jul 2018
- First submitted
- 14 Feb 2014
- Last updated
- 18 Jul 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02071888
- Acronym / sponsor ID
- CX-839-002
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Calithera Biosciences, IncIndustry (pharma, biotech, devices)
- Study start
- Feb 2014
- Primary completion
- Apr 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 26 Feb 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| CB-839 | Experimental | Drug: CB-839CB-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 |
| CB-839 and low dose dexamethasone | Experimental | Drug: CB-839, Drug: CB-839 and low dose dexamethasoneCB-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 |
| CB-839, pomalidomide, and low dose dexamethasone | Experimental | Drug: CB-839, Drug: CB-839 and low dose dexamethasone, Drug: CB-839, pomalidomide, and low dose dexamethasoneCB-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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CB-839Glutaminase inhibitor | Drug | CB-839, CB-839 and low dose dexamethasone, CB-839, pomalidomide, and low dose dexamethasone |
| CB-839 and low dose dexamethasoneAlso: CBdCB-839 and low dose dexamethasone | Drug | CB-839 and low dose dexamethasone, CB-839, pomalidomide, and low dose dexamethasone |
| CB-839, pomalidomide, and low dose dexamethasoneAlso: CBPdCB-839, pomalidomide, and low dose dexamethasone | Drug | CB-839, pomalidomide, and low dose dexamethasone |
Primary outcome
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
3 secondary outcomes
Pharmacokinetics: Area under the Curve (AUC) of CB-839 concentration in blood
Time frame: Study Days 1, 15, and 22
Pharmacodynamics: % inhibition of glutaminase in blood
Time frame: Study Days 1 and 15
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Keith W Orford, MD, PhD study director
Calithera Biosciences
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CB-839, CB-839 and low dose dexamethasone and CB-839, pomalidomide, and low dose dexamethasone in people with Non-Hodgkin's Lymphoma (NHL) and Multiple Myeloma, run by Calithera Biosciences, Inc at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2018.