This study is NOT currently recruiting participants.
Number
000356-C
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: Completed Study; data analyses ongoing Gender: Male & Female Min Age: 18 Years Max Age: N/A
Referral Letter Required
No
Population Exclusion(s)
Fetuses;Pregnant Women;Children
Keywords
heterogenous clonal diseases neoplasms; Interleukin-8; DNA methyltransferase inhibitors; cytopenias; Allogeneic Hematopoietic Stem Cell Transplantation
Recruitment Keyword(s)
None
Condition(s)
Myelodysplastic Syndromes
Investigational Drug(s)
BMS-986253 Inqovi (decitabine and cedazuridine)
Investigational Device(s)
Intervention(s)
Drug: Deoxyribonucleic acid (DNA) methyltransferase inhibitors (DNMTi) Decitabine Drug: Deoxyribonucleic acid (DNA) methyltransferase inhibitors (DNMTi) Cedazuridine Drug: BMS-986253 Procedure/Surgery: Bone Marrow Biopsy Procedure/Surgery: Bone Marrow Aspiration Procedure/Surgery: ECG
Supporting Site
National Cancer Institute
The myelodysplastic syndromes (MDS) are a group of bone marrow neoplasms. MDS mostly affect elderly people. The drugs used to treat MDS are not always effective, and the only curative treatment is stem cell transplant. Researchers want to see if a new drug can be used to treat MDS.
Objective:
To learn if BMS-986253 is a safe and effective treatment for MDS.
Eligibility:
Adults aged 18 and older with MDS.
Design:
Participants will be screened with a medical history, medication review, and physical exam. They will answer questions about how well they are able to take care of themselves. Their temperature, blood pressure, breathing rate, and heart rate will be monitored. They will have an electrocardiogram to see how well their heart is working. They will give blood and urine samples. They may have a bone marrow biopsy.
Participants will be assigned to a specific group. They will receive either BMS-986253 alone or in combination with deoxyribonucleic acid (DNA) methyltransferase inhibitors (DNMTi).
Treatment will be given in 28-day cycles. Participants will get BMS-986253 as an infusion on days 1 and 15 of each cycle. Some participants also will take oral DNMTi on days 2-6 of each cycle. They will receive treatment until their disease gets worse or they have bad side effects.
At study visits, some screening tests will be repeated. Some of the samples that are collected will be used for genetic testing.
About 30 days after treatment ends, participants will have a follow-up visit to see how they are doing. After that, follow up will occur via phone every 3-6 months until the study ends.
NIH will cover the costs for some travel expenses.
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INCLUSION CRITERIA: -Participants must have histologically or cytologically confirmed MDS according to 2016 WHO criteria -And: --have HR-MDS (R-IPSS >= 3.5) and received a minimum of 2 and maximum of 8 prior cycles for phase I and 4 for phase II of DNMTi therapy, or --have LR-MDS (R-IPSS <3.5), ---and, at least one cytopenia: ----granulocytes < 1.0 x 10^9/L and/or ----hemoglobin < 110 g/L with signs/symptoms of symptomatic anemia or transfusion-dependency ----platelets < 100 x 10^9/L -Age >=18 years --Because no dosing or adverse event data are currently available on the use of BMS-986253 as monotherapy or in combination with DNMTi in participants <18 years of age, children are excluded from this study, but will be eligible for future pediatric trials. -Eastern Cooperative Oncology Group (ECOG) performance status <=2 (Karnofsky >=60%). -Life expectancy greater than 6 months. -Participants must have adequate organ function as defined below: --total bilirubin <=1.5 X institutional upper limit of normal OR <=3 X institutional upper limit of normal in participants with Gilbert s syndrome (*except for participants with increased bilirubin levels attributed to intramedullary hemolysis, which will be allowable) -Aspartate aminotransferase (AST)/Serum glutamic oxaloacetic transaminase (SGOT)/Alanine transaminase (ALT)/Serum glutamic-pyruvic transaminase (SGPT) <=3 X institutional upper limit of normal OR <=5 X institutional upper limit of normal if related to disease specific cause -creatinine clearance >=60 mL/min/1.73 m^2 for participants with (by Cockcroft-Gault) creatinine levels above institutional normal. -The effects of BMS-986253 on the developing human fetus are unknown. For this reason and because DNMTi as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and up to 6 months after study completion and last dose of DNMTi. -Ability of subject to understand and the willingness to sign a written informed consent document. EXCLUSION CRITERIA: -For phase I: Participants with HR-MDS (R-IPSS >=3.5) that have not yet received or received less than 2 cycles of DNMTi therapy. -Participants with LR-MDS (R-IPSS <3.5) with the following characteristics that have not yet received or are still deriving benefit from the following standard of care therapies: --Hemoglobin (Hgb) <10 g/dL, Epo level <500 mU/mL: Erythropoietin-stimulating agents (ESAs) --MDS with del5q: Lenalidomide --MDS with ringed sideroblasts (MDS-RS) with SF3B1 mutation: Luspatercept -Participants with platelet transfusion-refractory thrombocytopenia, with inability to keep platelet threshold above 10K/mcL with transfusions or those with ongoing or uncontrolled hemorrhagic complications. -Participants with clinically significant neutropenia, ANC<100, with frequent hospitalizations for infection (average >1 hospitalization per month in past 6 months) -Participants who are receiving or have received any other investigational agents within 28 days before start of study treatment. -History of allergic reactions attributed to compounds of similar chemical or biologic composition to DNMTi or other agents used in study. -Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. -Pregnant women or women presently breast-feeding their children are excluded due to unknown risks to a developing fetus or infant. -Any significant disease that, in the opinion of the investigator, may impair the participant s tolerance of study treatment. -Active or uncontrolled autoimmune diseases requiring treatment. -Chronic hepatitis B or C infection, because potential immune impairment caused by these disorders may diminish the effectiveness of this immunologic therapy. -Human immunodeficiency virus (HIV)-positive participants are ineligible because of the potential for decreased immune response. -Presence of any other malignancy (except basal and squamous cell carcinoma of the skin, or stable chronic cancers on hormone or targeted therapy) for which participant received systemic anticancer treatment within 24 months prior to enrollment. -Prior history of allogeneic hematopoietic stem cell transplantation.
-Participants must have histologically or cytologically confirmed MDS according to 2016 WHO criteria
-And:
--have HR-MDS (R-IPSS >= 3.5) and received a minimum of 2 and maximum of 8 prior cycles for phase I and 4 for phase II of DNMTi therapy, or
--have LR-MDS (R-IPSS <3.5),
---and, at least one cytopenia:
----granulocytes < 1.0 x 10^9/L and/or
----hemoglobin < 110 g/L with signs/symptoms of symptomatic anemia or transfusion-dependency
----platelets < 100 x 10^9/L
-Age >=18 years
--Because no dosing or adverse event data are currently available on the use of BMS-986253 as monotherapy or in combination with DNMTi in participants <18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
-Eastern Cooperative Oncology Group (ECOG) performance status <=2 (Karnofsky >=60%).
-Life expectancy greater than 6 months.
-Participants must have adequate organ function as defined below:
--total bilirubin <=1.5 X institutional upper limit of normal OR <=3 X institutional upper limit of normal in participants with Gilbert s syndrome (*except for participants with increased bilirubin levels attributed to intramedullary hemolysis, which will be allowable)
-Aspartate aminotransferase (AST)/Serum glutamic oxaloacetic transaminase (SGOT)/Alanine transaminase (ALT)/Serum glutamic-pyruvic transaminase (SGPT) <=3 X institutional upper limit of normal OR <=5 X institutional upper limit of normal if related to disease specific cause
-creatinine clearance >=60 mL/min/1.73 m^2 for participants with (by Cockcroft-Gault) creatinine levels above institutional normal.
-The effects of BMS-986253 on the developing human fetus are unknown. For this reason and because DNMTi as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and up to 6 months after study completion and last dose of DNMTi.
-Ability of subject to understand and the willingness to sign a written informed consent document.
EXCLUSION CRITERIA:
-For phase I: Participants with HR-MDS (R-IPSS >=3.5) that have not yet received or received less than 2 cycles of DNMTi therapy.
-Participants with LR-MDS (R-IPSS <3.5) with the following characteristics that have not yet received or are still deriving benefit from the following standard of care therapies:
--Hemoglobin (Hgb) <10 g/dL, Epo level <500 mU/mL: Erythropoietin-stimulating agents (ESAs)
--MDS with del5q: Lenalidomide
--MDS with ringed sideroblasts (MDS-RS) with SF3B1 mutation: Luspatercept
-Participants with platelet transfusion-refractory thrombocytopenia, with inability to keep platelet threshold above 10K/mcL with transfusions or those with ongoing or uncontrolled hemorrhagic complications.
-Participants with clinically significant neutropenia, ANC<100, with frequent hospitalizations for infection (average >1 hospitalization per month in past 6 months)
-Participants who are receiving or have received any other investigational agents within 28 days before start of study
treatment.
-History of allergic reactions attributed to compounds of similar chemical or biologic composition to DNMTi or other agents used in study.
-Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
-Pregnant women or women presently breast-feeding their children are excluded due to unknown risks to a developing fetus or infant.
-Any significant disease that, in the opinion of the investigator, may impair the participant s tolerance of study treatment.
-Active or uncontrolled autoimmune diseases requiring treatment.
-Chronic hepatitis B or C infection, because potential immune impairment caused by these disorders may diminish the effectiveness of this immunologic therapy.
-Human immunodeficiency virus (HIV)-positive participants are ineligible because of the potential for decreased immune response.
-Presence of any other malignancy (except basal and squamous cell carcinoma of the skin, or stable chronic cancers on hormone or targeted therapy) for which participant received systemic anticancer treatment within 24 months prior to enrollment.
-Prior history of allogeneic hematopoietic stem cell transplantation.
Principal Investigator
Referral Contact
For more information: