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Glutaminase Inhibitor CB-839 and Azacitidine in Treating Patients With Advanced Myelodysplastic Syndrome | Clinical Trials | Clareo Health

COMPLETEDPHASE1/PHASE2

Glutaminase Inhibitor CB-839 and Azacitidine in Treating Patients With Advanced Myelodysplastic Syndrome

Phase Ib/II Study of the Glutaminase Inhibitor CB-839 in Combination With Azacitidine in Patients With Advanced Myelodysplastic Syndrome

NCT03047993•M.D. Anderson Cancer Center

View on ClinicalTrials.gov

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. 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: I. 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: I. 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.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•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)
•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
+1 more criteria

Exclusion Criteria

•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
•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

Locations (1)

M D Anderson Cancer Center

Houston, Texas, United States

Key Dates

Start Date

November 15, 2017

Primary Completion Date

March 16, 2023

Completion Date

March 16, 2023

Last Updated

May 14, 2024

Enrollment

ACTUAL participants

Conditions

Acute Myeloid Leukemia With Multilineage DysplasiaBlasts 20-30 Percent of Bone Marrow Nucleated CellsBlasts 20-30 Percent of Peripheral Blood White CellsChronic Myelomonocytic LeukemiaHigh Risk Myelodysplastic SyndromeIPSS Risk Category Intermediate-2Myelodysplastic Syndrome

Interventions

Azacitidine

DRUG

Glutaminase Inhibitor CB-839

DRUG

Donor Umbilical Cord Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies

NCT01093586

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic SyndromeAdult Acute Lymphoblastic Leukemia in Remission+74 more

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TERMINATEDPHASE2

Bortezomib in Treating Patients With High-Risk Acute Myeloid Leukemia in Remission

NCT01465386

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic SyndromeAdult Acute Minimally Differentiated Myeloid Leukemia (M0)+10 more

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: May 14, 2024Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

Glutaminase Inhibitor CB-839 and Azacitidine in Treating Patients With Advanced Myelodysplastic Syndrome

Inclusion Criteria

Exclusion Criteria

Donor Umbilical Cord Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies

Bortezomib in Treating Patients With High-Risk Acute Myeloid Leukemia in Remission

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