Description:
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.
Title
- Brief Title: Glutaminase Inhibitor CB-839 and Azacitidine in Treating Patients With Advanced Myelodysplastic Syndrome
- Official Title: Phase Ib/II Study of the Glutaminase Inhibitor CB-839 in Combination With Azacitidine in Patients With Advanced Myelodysplastic Syndrome
Clinical Trial IDs
- ORG STUDY ID:
2016-0636
- SECONDARY ID:
NCI-2018-01243
- SECONDARY ID:
2016-0636
- SECONDARY ID:
P30CA016672
- SECONDARY ID:
R01CA206210
- NCT ID:
NCT03047993
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
- Myelodysplastic Syndrome
Interventions
Drug | Synonyms | Arms |
---|
Azacitidine | 5 AZC, 5-AC, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, U-18496, Vidaza | Treatment (glutaminase inhibitor CB-839, azacitidine) |
Glutaminase Inhibitor CB-839 | CB-839 | Treatment (glutaminase inhibitor CB-839, azacitidine) |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
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. | - Azacitidine
- Glutaminase Inhibitor CB-839
|
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Incidence of adverse events Common Toxicity Criteria version 4.0 |
Time Frame: | Up to 4 years |
Safety Issue: | |
Description: | Safety data will be summarized using frequency and percentage, by category and severity. |
Secondary Outcome Measures
Measure: | Rates of response (complete response + partial response) to therapy |
Time Frame: | Up to 4 years |
Safety Issue: | |
Description: | Will be estimated along with the 95% confidence interval. |
Measure: | Event-free survival |
Time Frame: | Up to 4 years |
Safety Issue: | |
Description: | The Kaplan-Meier method will be used to estimate the probabilities. Log-rank tests will be used to compare among subgroups of patients. |
Measure: | Overall survival |
Time Frame: | Up to 4 years |
Safety Issue: | |
Description: | The Kaplan-Meier method will be used to estimate the probabilities. Log-rank tests will be used to compare among subgroups of patients. |
Measure: | Duration of response |
Time Frame: | Up to 4 years |
Safety Issue: | |
Description: | The Kaplan-Meier method will be used to estimate the probabilities. Log-rank tests will be used to compare among subgroups of patients. |
Measure: | Anti-tumor activity |
Time Frame: | Up to 4 years |
Safety Issue: | |
Description: | Will be summarized graphically and with descriptive statistics. |
Measure: | Pharmacodynamic markers |
Time Frame: | Up to 4 years |
Safety Issue: | |
Description: | Will be summarized graphically and with descriptive statistics. |
Measure: | Exploratory biomarkers |
Time Frame: | Up to 4 years |
Safety Issue: | |
Description: | Will be summarized graphically and with descriptive statistics. |
Measure: | Drug exposure levels |
Time Frame: | Up to 4 years |
Safety Issue: | |
Description: | Will be summarized graphically and with descriptive statistics. |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | M.D. Anderson Cancer Center |
Last Updated
January 15, 2021