NCT03047993 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1, PHASE2
Status at capture: COMPLETED
Registry last update: 2024-05-14

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Number of Participants With a Response

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: 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 * 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 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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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.
intervention Names
Drug: Azacitidine
Drug: Glutaminase Inhibitor CB-839
label
Treatment (glutaminase inhibitor CB-839, azacitidine)
type
EXPERIMENTAL

interventions

arm Group Labels
Treatment (glutaminase inhibitor CB-839, azacitidine)
description
Given IV or SC
name
Azacitidine
other Names
5 AZC
5-AC
5-Azacytidine
5-AZC
Azacytidine
Azacytidine, 5-
Ladakamycin
Mylosar
U-18496
Vidaza
type
DRUG
arm Group Labels
Treatment (glutaminase inhibitor CB-839, azacitidine)
description
Given PO
name
Glutaminase Inhibitor CB-839
other Names
CB-839
type
DRUG

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 28
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Number of Participants With a Response
time Frame
Up to 5 years, 4 months

Full study description

brief 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.

Source references

references

citation
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.
pmid
39300320
type
DERIVED