Acute Myeloid Leukemia With Multilineage DysplasiaPhase 1/2NCT03047993
Glutaminase Inhibitor CB-839 and Azacitidine in Treating Patients With Advanced Myelodysplastic Syndrome
A Phase 1/2 study testing Azacitidine and Glutaminase Inhibitor CB-839 in people with Acute Myeloid Leukemia With Multilineage Dysplasia and Blasts 20-30 Percent of Bone Marrow Nucleated Cells, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase I/II trial studies the side effects of glutaminase inhibitor CB-839 in combination with azacitidine in treating patients with myelodysplastic syndrome that has spread to other places in the body. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia With Multilineage Dysplasia, Blasts 20-30 Percent of Bone Marrow Nucleated Cells, Blasts 20-30 Percent of Peripheral Blood White Cells
- What is being tested?
- Azacitidine and Glutaminase Inhibitor CB-839
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Nov 2017to 16 Mar 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Signed, informed consent must be obtained prior to any study specific procedures
- Subjects with a histologically confirmed diagnosis of MDS, including both MDS and refractory anemia with excess blasts (RAEB)-T (acute myeloid leukemia [AML] with 20-30% blasts and multilineage dysplasia by French-American-British [FAB] criteria) by World Health Organization (WHO) and chronic myelomonocytic leukemia (CMML) are eligible
- Subjects with high-risk MDS (i.e. International Prognostic Scoring System [IPSS] Intermediate-2 or high-risk; or R-IPSS high or very-high risk). Patients with Intermediate-1 risk by IPSS or Intermediate risk by R-IPSS and with IDH1 or IDH2, or high-risk molecular features including TP53, ASXL1, EZH2, and/or RUNX1 mutations are also eligible
- Subjects with prior hypomethylating agent therapy exposure may be eligible based on discussion with the principal investigator (PI)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Serum bilirubin =< 2 x the upper limit of normal (ULN) (except for patients with Gilbert's disease)
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- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 3 x the laboratory ULN
- Creatinine clearance > 30 mL/min based on the Cockcroft-Gault equation
- Able to understand and voluntarily sign a written informed consent, and willing and able to comply with protocol requirements
- Resolution of all treatment-related, non-hematological toxicities, except alopecia, from any previous cancer therapy to < grade 1 prior to the first dose of study treatment
- Female patients of childbearing potential must have a negative serum or urine pregnancy test within 3 days of the first dose of study drug and agree to use dual methods of contraception during the study and for a minimum of 3 months following the last dose of study drug. Post-menopausal females (>= 45 years old and without menses for >= 1 year) and surgically sterilized females are exempt from these requirements. Male patients must use an effective barrier method of contraception during the study and for a minimum of 3 months following the last dose of study drug if sexually active with a female of childbearing potential
Who cannot join
- Any prior or coexisting medical condition that in the investigator's judgment will substantially increase the risk associated with the subject's participation in the study
- Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures
- Active uncontrolled infection at study enrollment including known diagnosis of human immunodeficiency virus or chronic active hepatitis B or C infection
- Clinically significant gastrointestinal conditions or disorders that may interfere with study drug absorption, including prior gastrectomy
- Patients with known active central nervous system (CNS) disease, including leptomeningeal involvement
- Impaired cardiac function, uncontrolled cardiac arrhythmia, or clinically significant cardiac disease including the following: a) New York Heart Association grade III or IV congestive heart failure, b) myocardial infarction within the last 6 months
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- Subjects with a corrected QT (QTc) > 480 ms (QTc > 510 msec for subjects with a bundle branch block at baseline)
- Nursing or pregnant women
- Subjects with known hypersensitivity to study drugs or their excipients
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase Ib/II Study of the Glutaminase Inhibitor CB-839 in Combination With Azacitidine in Patients With Advanced Myelodysplastic Syndrome
This phase I/II trial studies the side effects of glutaminase inhibitor CB-839 in combination with azacitidine in treating patients with myelodysplastic syndrome that has spread to other places in the body. Glutaminase inhibitor CB-839 and azacitidine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the safety, tolerability and clinical activity of glutaminase inhibitor CB-839 (CB-839) in combination with azacitidine (AZA) for patients with advanced myelodysplastic syndrome (MDS).
SECONDARY OBJECTIVES:
- To explore the pharmacokinetics (PK) of CB-839 in combination with AZA. II. To explore the pharmacodynamics (PDn) of CB-839 in combination with AZA. III. To assess overall survival, event-free survival and duration of response of CB-839 in combination with AZA.
OUTLINE:
Patients receive glutaminase inhibitor CB-839 orally (PO) twice daily (BID) on days 1-28 and azacitidine subcutaneously (SC) or intravenously (IV) over 10-40 minutes on days 1-7.
After completion of study treatment, patients are followed up at 28 days.
- Conditions
- Acute Myeloid Leukemia With Multilineage Dysplasia, Blasts 20-30 Percent of Bone Marrow Nucleated Cells, Blasts 20-30 Percent of Peripheral Blood White Cells, Chronic Myelomonocytic Leukemia, High Risk Myelodysplastic Syndrome, IPSS Risk Category Intermediate-2
- Being tested
- Azacitidine, Glutaminase Inhibitor CB-839
- Medical subject headings
- Leukemia, Myelomonocytic, Chronic, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzacitidineDrug
Also called 5 AZC, 5-AC, 5-Azacytidine, 5-AZC
Given IV or SC
Glutaminase Inhibitor CB-839Drug
Also called CB-839
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (glutaminase inhibitor CB-839, azacitidine) | Experimental | Patients receive glutaminase inhibitor CB-839 PO BID on days 1-28 and azacitidine SC or IV over 10-40 minutes on days 1-7. Receives: Drug: Azacitidine; Drug: Glutaminase Inhibitor CB-839 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With a Response
Response is Complete Remission (CR) + Partial Remission (PR) + Marrow CR = Complete Remission (CR) is </=5% myeloblasts with normal maturation of all cell lines* Persistent dysplasia will be noted, Peripheral blood; hemoglobin>/=11 g/dL, Platelets >/= 100x10^9/L ,Neutrophils >/=1.0 x 10^9/L, Blasts = 0%. Partial Remission (PR) is all CR criteria if abnormal before treatment except: Bone marrow blasts decreased by </=50% over pretreatment but still >5% Cellularity and morphology not relevant. Marrow CR is Bone marrow: </= 5% meyloblasts and decreased by >/= 50% over pretreatment† Peripheral blood: if HI responses, they will be noted in addition to marrow CR.
Measured: Up to 5 years, 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2017 (estimated)
- Study start15 Nov 2017
- Primary completion16 Mar 2023
- Study completion16 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid Leukemia With Multilineage DysplasiaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Courtney DiNardo, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03047993
- Sponsor's protocol ID
- 2016-0636
- Other IDs
- NCI-2018-01243, 2016-0636, R01CA206210
- Status last verified
- Apr 2024
- First submitted
- 3 Feb 2017
- Last updated
- 14 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
DiNardo CD, Verma D, Baran N, Bhagat TD, Skwarska A, Lodi A, Saxena K, Cai T, Su X, Guerra VA, Poigaialwar G, Kuruvilla VM, Konoplev S, Gordon-Mitchell S, Pradhan K, Aluri S, Hackman GL, Chaudhry S, Collins M, Sweeney SR, Busquets J, Rathore AS, Deng Q, Green MR, Grant S, Demo S, Choudhary GS, Sahu S, Agarwal B, Spodek M, Thiruthuvanathan V, Will B, Steidl U, Tippett GD, Burger J, Borthakur G, Jabbour E, Pemmaraju N, Kadia T, Kornblau S, Daver NG, Naqvi K, Short NJ, Garcia-Manero G, Tiziani S, Verma A, Konopleva M. Glutaminase inhibition in combination with azacytidine in myelodysplastic syndromes: a phase 1b/2 clinical trial and correlative analyses. Nat Cancer. 2024 Oct;5(10):1515-1533. doi: 10.1038/s43018-024-00811-3. Epub 2024 Sep 19.
PubMed 39300320
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib/II Study of the Glutaminase Inhibitor CB-839 in Combination With Azacitidine in Patients With Advanced Myelodysplastic Syndrome
- ClinicalTrials.gov ID
- NCT03047993
- Acronym / sponsor ID
- 2016-0636
- Conditions
- Acute Myeloid Leukemia With Multilineage Dysplasia, Blasts 20-30 Percent of Bone Marrow Nucleated Cells, Blasts 20-30 Percent of Peripheral Blood White Cells, Chronic Myelomonocytic Leukemia, High Risk Myelodysplastic Syndrome, IPSS Risk Category Intermediate-2
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 15 Nov 2017 (actual)
- Primary completion
- 16 Mar 2023 (actual)
- Study completion
- 16 Mar 2023 (actual)
- First posted
- 9 Feb 2017 (estimated)
- Results
- Posted 14 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I/II trial studies the side effects of glutaminase inhibitor CB-839 in combination with azacitidine in treating patients with myelodysplastic syndrome that has spread to other places in the body. Glutaminase inhibitor CB-839 and azacitidine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVES:
- To determine the safety, tolerability and clinical activity of glutaminase inhibitor CB-839 (CB-839) in combination with azacitidine (AZA) for patients with advanced myelodysplastic syndrome (MDS).
SECONDARY OBJECTIVES:
- To explore the pharmacokinetics (PK) of CB-839 in combination with AZA. II. To explore the pharmacodynamics (PDn) of CB-839 in combination with AZA. III. To assess overall survival, event-free survival and duration of response of CB-839 in combination with AZA.
OUTLINE:
Patients receive glutaminase inhibitor CB-839 orally (PO) twice daily (BID) on days 1-28 and azacitidine subcutaneously (SC) or intravenously (IV) over 10-40 minutes on days 1-7.
After completion of study treatment, patients are followed up at 28 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (glutaminase inhibitor CB-839, azacitidine) | Experimental | Drug: Azacitidine, Drug: Glutaminase Inhibitor CB-839Patients receive glutaminase inhibitor CB-839 PO BID on days 1-28 and azacitidine SC or IV over 10-40 minutes on days 1-7. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Signed, informed consent must be obtained prior to any study specific procedures
- Subjects with a histologically confirmed diagnosis of MDS, including both MDS and refractory anemia with excess blasts (RAEB)-T (acute myeloid leukemia [AML] with 20-30% blasts and multilineage dysplasia by French-American-British [FAB] criteria) by World Health Organization (WHO) and chronic myelomonocytic leukemia (CMML) are eligible
- Subjects with high-risk MDS (i.e. International Prognostic Scoring System [IPSS] Intermediate-2 or high-risk; or R-IPSS high or very-high risk). Patients with Intermediate-1 risk by IPSS or Intermediate risk by R-IPSS and with IDH1 or IDH2, or high-risk molecular features including TP53, ASXL1, EZH2, and/or RUNX1 mutations are also eligible
- Subjects with prior hypomethylating agent therapy exposure may be eligible based on discussion with the principal investigator (PI)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Key exclusion criteria (9 listed)
- Any prior or coexisting medical condition that in the investigator's judgment will substantially increase the risk associated with the subject's participation in the study
- Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures
- Active uncontrolled infection at study enrollment including known diagnosis of human immunodeficiency virus or chronic active hepatitis B or C infection
- Clinically significant gastrointestinal conditions or disorders that may interfere with study drug absorption, including prior gastrectomy
- Patients with known active central nervous system (CNS) disease, including leptomeningeal involvement
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 |
|---|---|---|
| AzacitidineAlso: 5 AZC, 5-AC, 5-Azacytidine, 5-AZCGiven IV or SC | Drug | Treatment (glutaminase inhibitor CB-839, azacitidine) |
| Glutaminase Inhibitor CB-839Also: CB-839Given PO | Drug | Treatment (glutaminase inhibitor CB-839, azacitidine) |
Primary outcome
Number of Participants With a Response
Time frame: Up to 5 years, 4 months
Response is Complete Remission (CR) + Partial Remission (PR) + Marrow CR = Complete Remission (CR) is </=5% myeloblasts with normal maturation of all cell lines* Persistent dysplasia will be noted, Peripheral blood; hemoglobin>/=11 g/dL, Platelets >/= 100x10^9/L ,Neutrophils >/=1.0 x 10^9/L, Blasts = 0%. Partial Remission (PR) is all CR criteria if abnormal before treatment except: Bone marrow blasts decreased by </=50% over pretreatment but still >5% Cellularity and morphology not relevant. Marrow CR is Bone marrow: </= 5% meyloblasts and decreased by >/= 50% over pretreatment† Peripheral blood: if HI responses, they will be noted in addition to marrow CR.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39300320DiNardo CD, Verma D, Baran N, Bhagat TD, Skwarska A, Lodi A, Saxena K, Cai T, Su X, Guerra VA, Poigaialwar G, Kuruvilla VM, Konoplev S, Gordon-Mitchell S, Pradhan K, Aluri S, Hackman GL, Chaudhry S, Collins M, Sweeney SR, Busquets J, Rathore AS, Deng Q, Green MR, Grant S, Demo S, Choudhary GS, Sahu S, Agarwal B, Spodek M, Thiruthuvanathan V, Will B, Steidl U, Tippett GD, Burger J, Borthakur G, Jabbour E, Pemmaraju N, Kadia T, Kornblau S, Daver NG, Naqvi K, Short NJ, Garcia-Manero G, Tiziani S, Verma A, Konopleva M. Glutaminase inhibition in combination with azacytidine in myelodysplastic syndromes: a phase 1b/2 clinical trial and correlative analyses. Nat Cancer. 2024 Oct;5(10):1515-1533. doi: 10.1038/s43018-024-00811-3. Epub 2024 Sep 19.
- MD Anderson Cancer CenterLink provided by the sponsor.
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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.
Courtney DiNardo principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Azacitidine and Glutaminase Inhibitor CB-839 in people with Acute Myeloid Leukemia With Multilineage Dysplasia and Blasts 20-30 Percent of Bone Marrow Nucleated Cells, run by M.D. Anderson Cancer Center at 1 site 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 11 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 14 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With a Response (time frame: Up to 5 years, 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03047993, which also lists 1 linked publication.
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 14 May 2024.