Trial reportNature cancer2024
Glutaminase inhibition in combination with azacytidine in myelodysplastic syndromes: a phase 1b/2 clinical trial and correlative analyses.
Registry-linked trialAbstract readClinical Trial, Phase IClinical Trial, Phase II
In one paragraph
Trial report in Nature cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03047993 (Phase Ib/II Study of the Glutaminase Inhibitor CB-839 in Combination With Azacitidine in Patients With Advanced Myelodysplastic Syndrome), which is not on this map. Cited by 33 papers.
0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
–field-weighted citation impact
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase Ib/II Study of the Glutaminase Inhibitor CB-839 in Combination With Azacitidine in Patients With Advanced Myelodysplastic Syndrome
Who cites it
33 citing papers in PubMed.
- Trial
- Exploiting Metabolic Vulnerabilities in Acute Myeloid Leukemia: Rationale and Evidence for Combining Metabolic Modulators with Conventional Chemotherapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Metabolism, autophagy, and cell death: The triangular axis in tumor survival and therapeutic resistance.Redox biology · 2026Review
- Targeting MYC-Driven Cancers: From Oncogenic Addiction to Therapeutic Vulnerability.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Unraveling the role of glutamine metabolism in cancer: from cell death mechanisms to tumor microenvironment modulation.Experimental hematology & oncology · 2026Review
- 70 Years of DON and Beyond: Glutaminase Inhibition as a Synergistic Strategy in Cancer Combination Therapy.Pharmaceutics · 2026Review
- Metabolites as signalling molecules in the tumour immune microenvironment.Nature reviews. Immunology · 2026Review
- Metabolic Crosstalk Between Host and Tumor as a Circuit of Resilience in Cancer Therapy.Cells · 2026Review
- The metabolic profiles of cancer stem cells.Stem cell research & therapy · 2026Review
- The SWI/SNF complex in tumor metabolism: Mechanisms and therapeutic implications.The Journal of biological chemistry · 2026Review
- A STAT3 degrader demonstrates efficacy in venetoclax resistant acute myeloid leukemia.Leukemia · 2026Article
- Glutaminase 1 in Vascular Disease: Linking Metabolic Reprogramming to Atherosclerosis Progression and Stability.Journal of cardiovascular translational research · 2026Review
- ProteinbioRxiv : the preprint server for biology · 2026Article
- Fueling the Fire: How Glutamine Metabolism Sustains Leukemia Growth and Resistance.BioMed (Basel, Switzerland) · 2026Article
- Targeting MDSCs in cancer: emerging immunotherapeutic and metabolic strategies.Frontiers in immunology · 2026Review
- Glutamine Metabolism: Role in Cancer Cell Proliferation and Survival.Cancer treatment and research · 2026Review
- Stroma-driven horizontal transfer of TCA-related proteins mediates metabolic plasticity and imatinib resistance in chronic myeloid leukemia.Cell communication and signaling : CCS · 2025Article
- Metabolomic Investigation of Myelodysplastic Syndromes, Multiple Myeloma, and Homozygous β-Thalassemia.Cells · 2025Review
- Review
- Small-molecule OPA1 inhibitors reverse mitochondrial adaptations to overcome therapy resistance in acute myeloid leukemia.Science advances · 2025Article
Corrections and comments
- Update of
Authors and funding
47 authors.
Courtney D DiNardo *Departament of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-9003-0390
Divij Verma *Department of Medicine (Oncology), Blood Cancer Institute, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.ORCID http://orcid.org/0000-0002-2214-9450
Natalia Baran *Departament of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0003-0618-4798
Tushar D Bhagat *Department of Medicine (Oncology), Blood Cancer Institute, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.
Anna Skwarska *Department of Medicine (Oncology), Blood Cancer Institute, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.
Alessia Lodi *Department of Nutritional Sciences, College of Natural Sciences, The University of Texas at Austin, Austin, TX, USA.
Kapil SaxenaDepartament of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Tianyu CaiDepartament of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-5271-3235
Xiaoping SuDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Veronica A GuerraDepartament of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-4219-7708
Gowri PoigaialwarDepartment of Medicine (Oncology), Blood Cancer Institute, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.ORCID http://orcid.org/0000-0002-8882-7146
Vinitha M KuruvillaDepartament of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Sergej KonoplevDepartment of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Shanisha Gordon-MitchellDepartment of Medicine (Oncology), Blood Cancer Institute, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.
Kith PradhanDepartment of Medicine (Oncology), Blood Cancer Institute, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.
Srinivas AluriDepartment of Medicine (Oncology), Blood Cancer Institute, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.
G Lavender HackmanDepartment of Nutritional Sciences, College of Natural Sciences, The University of Texas at Austin, Austin, TX, USA.ORCID http://orcid.org/0000-0001-7439-5138
Sovira ChaudhryDepartment of Medicine (Oncology), Blood Cancer Institute, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.
Meghan CollinsDepartment of Nutritional Sciences, College of Natural Sciences, The University of Texas at Austin, Austin, TX, USA.ORCID http://orcid.org/0000-0002-6201-9298
Shannon R SweeneyDell Pediatric Research Institute, Department of Pediatrics, Dell Medical School, The University of Texas at Austin, Austin, TX, USA.
Jonathan BusquetsDepartment of Nutritional Sciences, College of Natural Sciences, The University of Texas at Austin, Austin, TX, USA.
Atul Singh RathoreDepartment of Nutritional Sciences, College of Natural Sciences, The University of Texas at Austin, Austin, TX, USA.
Qing DengDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Michael R GreenDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-6309-9472
Steven GrantDivision of Hematology/Oncology, Department of Medicine, Virginia Commonwealth University, Richmond, VA, USA.
Susan DemoCalithera Biosciences, San Francisco, CA, USA.
Gaurav S ChoudharyDepartment of Medicine (Oncology), Blood Cancer Institute, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.
Srabani SahuDepartment of Medicine (Oncology), Blood Cancer Institute, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.
Beamon AgarwalGenomeRxUS, Secane, PA, USA.
Mason SpodekDepartment of Medicine (Oncology), Blood Cancer Institute, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.
Victor ThiruthuvanathanDepartment of Medicine (Oncology), Blood Cancer Institute, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.
Britta WillDepartment of Medicine (Oncology), Blood Cancer Institute, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.
Ulrich SteidlDepartment of Medicine (Oncology), Blood Cancer Institute, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.
George D TippettDepartament of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jan BurgerDepartament of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Gautam BorthakurDepartament of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-7679-6453
Elias JabbourDepartament of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0003-4465-6119
Naveen PemmarajuDepartament of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Tapan KadiaDepartament of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-9892-9832
Steven KornblauDepartament of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-5990-9548
Naval G DaverDepartament of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-7103-373X
Kiran NaqviDepartament of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Nicholas J ShortDepartament of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Guillermo Garcia-ManeroDepartament of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-3631-2482
Stefano TizianiDepartment of Nutritional Sciences, College of Natural Sciences, The University of Texas at Austin, Austin, TX, USA. tiziani@utexas.edu.ORCID http://orcid.org/0000-0002-7230-0307
Amit VermaDepartment of Medicine (Oncology), Blood Cancer Institute, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA. amit.verma@einsteinmed.edu.ORCID http://orcid.org/0000-0002-5408-1673
Marina KonoplevaDepartament of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. marina.konopleva@einsteinmed.edu.ORCID http://orcid.org/0000-0002-9347-2212
Funding
TRAINING FOR ACADEMIC ONCOLOGY/HEMATOLOGYT32CA009666 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Michael Davies, Courtney DiNardo · 1994 to 2026
$9.8MIdentification and targeting of pathways separating healthy stem cell aging from malignant transformationR01CA230756 · NCI · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI Britta Will · 2018 to 2026
$4.0MTherapeutic targeting of glutamine metabolism in MDSR01CA206210 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KONOPLEVA, MARINA Y, TIZIANI, STEFANO · 2016 to 2020
$2.4MNCI NIH HHS R01 CA206210NCI NIH HHS R01 CA230756NCI NIH HHS T32 CA009666
Abstract
Malignancies are reliant on glutamine as an energy source and a facilitator of aberrant DNA methylation. We demonstrate preclinical synergy of telaglenastat (CB-839), a selective glutaminase inhibitor, combined with azacytidine (AZA), followed by a single-arm, open-label, phase 1b/2 study in persons with advanced myelodysplastic syndrome (MDS). The dual primary endpoints evaluated clinical activity, safety and tolerability; secondary endpoints evaluated pharmacokinetics, pharmacodynamics, overall survival, event-free survival and duration of response. The dose-escalation study included six participants and the dose-expansion study included 24 participants. Therapy was well tolerated and led to an objective response rate of 70% with (marrow) complete remission in 53% of participants and a median overall survival of 11.6 months, with evidence of myeloid differentiation in responders determined by single-cell RNA sequencing. Glutamine transporter solute carrier family 38 member 1 in MDS stem cells was associated with clinical responses and predictive of worse prognosis in a large MDS cohort. These data demonstrate the safety and efficacy of CB-839 and AZA as a combined metabolic and epigenetic approach in MDS. ClinicalTrials.gov identifier: NCT03047993 .
Indexed as
AzacitidineGlutaminaseMyelodysplastic SyndromesAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBenzeneacetamidesEnzyme InhibitorsFemaleHumansMaleMiddle AgedThiadiazolesAzacitidineBenzeneacetamidesCB-839Enzyme InhibitorsGlutaminaseThiadiazoles
Identifiers
What Socratic holds
Textmetadata
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Read underepoch 390
Registered trials
NCT03047993ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.