Brief Summary
The goal of this clinical trial is to learn about the safety and effectiveness of the combination drug Tetrahydrouridine (THU) and decitabine (DEC) to treat patients with relapsed or refractory myelodysplastic syndrome. The main questions it aims to answer are:
* Does the combination drug exhibit hematological and nonhematological toxicity?
* Does the combination drug improve health status and reduce the number of days of hospitalization?
Participants will:
* Take tetrahydrouridine and decitabine once a week for 24 weeks
* Visit the clinic once every 4 weeks for checkups and tests
* Keep a diary of their symptoms
* Does the combination drug exhibit hematological and nonhematological toxicity?
* Does the combination drug improve health status and reduce the number of days of hospitalization?
Participants will:
* Take tetrahydrouridine and decitabine once a week for 24 weeks
* Visit the clinic once every 4 weeks for checkups and tests
* Keep a diary of their symptoms
Brief Title
A Study of Oral Tetrahydrouridine-Decitabine in Relapsed or Refractory Myelodysplastic Syndromes (MDS)
Detailed Description
This is a single-arm, open-label Phase 1 study of oral THU/decitabine to treat relapsed or refractory MDS. Patients will be treated for 24 weeks in the absence of clear evidence of progressive disease. The primary endpoint is safety. The secondary endpoints will include assessment of response rates by International Working Group (IWG) criteria, quality of life (QoL), and number of days of hospitalization. DNA-methyltransferase 1 (DNMT1) protein levels will be measured in bone marrow and peripheral blood white cells.
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
201-618-4725
Central Contact Email
dhoban@montefiore.org
Completion Date
Completion Date Type
Estimated
Conditions
MDS
Eligibility Criteria
Inclusion Criteria:
* Patients must have a diagnosis of MDS that has received one or more prior standard therapies and is relapsed or refractory
* Patients must be 18 years of age or older
* Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 3
* Patients must have adequate end-organ function
* Patient's body weight must be ≥ 41 kg
* Subjects must be able to understand and willing to sign a written informed consent document and complete study-related procedures.
Exclusion Criteria:
* Diagnosis of acute promyelocytic leukemia (APL)
* Prior treatment with ≥4 28-day cycles of parenteral or oral decitabine
* No other disease-directed therapy, save for hydroxyurea, including experimental or investigational drug therapy for 14 days prior to study entry (hydroxyurea should be discontinued ≥24 hours prior to initiation of study drug)
* Requiring concomitant treatment with drugs that are cytidine deaminase (CDA) substrates and/or inhibitors, e.g., cytarabine, 5-azacytidine, gemcitabine
* Currently pregnant or breastfeeding. Females of childbearing potential must have a negative serum pregnancy test within 72 hours of treatment start.
* Uncontrolled intercurrent illness that could limit life expectancy or ability to complete study correlates
* Women of Childbearing Potential (WOCBP) who are unwilling to agree to use dual contraceptive measures (i.e., hormonal or barrier method of birth control; abstinence, condom) prior to study entry, for the duration of study participation, and until 6 months after taking the last dose of THU/decitabine
* Sexually active male who is unwilling to use a condom when engaging in any sexual contact with a WOCBP, beginning at the screening visit and continuing until 6 months after taking the last dose of THU/decitabine
* 9. Patients with uncontrolled active human retrovirus (HIV) infection, as this will further increase the risk for opportunistic infections. However, patients with HIV with undetectable viral load by polymerase chain reaction (PCR), without opportunistic infection, and on a stable regimen of antiretroviral therapy are eligible
* Patients must have a diagnosis of MDS that has received one or more prior standard therapies and is relapsed or refractory
* Patients must be 18 years of age or older
* Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 3
* Patients must have adequate end-organ function
* Patient's body weight must be ≥ 41 kg
* Subjects must be able to understand and willing to sign a written informed consent document and complete study-related procedures.
Exclusion Criteria:
* Diagnosis of acute promyelocytic leukemia (APL)
* Prior treatment with ≥4 28-day cycles of parenteral or oral decitabine
* No other disease-directed therapy, save for hydroxyurea, including experimental or investigational drug therapy for 14 days prior to study entry (hydroxyurea should be discontinued ≥24 hours prior to initiation of study drug)
* Requiring concomitant treatment with drugs that are cytidine deaminase (CDA) substrates and/or inhibitors, e.g., cytarabine, 5-azacytidine, gemcitabine
* Currently pregnant or breastfeeding. Females of childbearing potential must have a negative serum pregnancy test within 72 hours of treatment start.
* Uncontrolled intercurrent illness that could limit life expectancy or ability to complete study correlates
* Women of Childbearing Potential (WOCBP) who are unwilling to agree to use dual contraceptive measures (i.e., hormonal or barrier method of birth control; abstinence, condom) prior to study entry, for the duration of study participation, and until 6 months after taking the last dose of THU/decitabine
* Sexually active male who is unwilling to use a condom when engaging in any sexual contact with a WOCBP, beginning at the screening visit and continuing until 6 months after taking the last dose of THU/decitabine
* 9. Patients with uncontrolled active human retrovirus (HIV) infection, as this will further increase the risk for opportunistic infections. However, patients with HIV with undetectable viral load by polymerase chain reaction (PCR), without opportunistic infection, and on a stable regimen of antiretroviral therapy are eligible
Inclusion Criteria
Inclusion Criteria:
* Patients must have a diagnosis of MDS that has received one or more prior standard therapies and is relapsed or refractory
* Patients must be 18 years of age or older
* Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 3
* Patients must have adequate end-organ function
* Patient's body weight must be ≥ 41 kg
* Subjects must be able to understand and willing to sign a written informed consent document and complete study-related procedures.
* Patients must have a diagnosis of MDS that has received one or more prior standard therapies and is relapsed or refractory
* Patients must be 18 years of age or older
* Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 3
* Patients must have adequate end-organ function
* Patient's body weight must be ≥ 41 kg
* Subjects must be able to understand and willing to sign a written informed consent document and complete study-related procedures.
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT07006025
Org Class
Industry
Org Full Name
EpiDestiny, Inc.
Org Study Id
2024-00001
Overall Status
Recruiting
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
Phase 1 Study of Oral Tetrahydrouridine-Decitabine to Treat Relapsed or Refractory Myelodysplastic Syndromes
Primary Outcomes
Outcome Description
Measure neutrophils count
Outcome Measure
White blood cell measurement
Outcome Time Frame
every 4 weeks
Outcome Description
Measure platelets in the blood
Outcome Measure
Platelet count
Outcome Time Frame
every 4 week
Secondary Outcomes
Outcome Description
Measure using International Working Group (IWG) 2023 response criteria
Outcome Time Frame
every 4 weeks
Outcome Measure
Response for high-risk MDS
Outcome Description
Record the number of days of hospitalization
Outcome Time Frame
every 4 weeks
Outcome Measure
Hospitalization
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Mendel Goldfinger
Investigator Email
MGOLDFIN@MONTEFIORE.ORG
Investigator Phone
718-920-4826