Oral Tetrahydrouridine-Decitabine in Patients With Advanced Myeloproliferative Neoplasms
An Open-Label, Phase II Study Evaluating the Feasibility, Safety, and Efficacy of Oral Tetrahydrouridine-Decitabine in Patients With Advanced Myeloproliferative Neoplasms
Who can join
As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.
- Age
- 18 Years and older
- Sex
- All sexes
- Healthy volunteers
- Not accepted
- Compensation
- Mentioned in the study description
Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.
What to expect
No one can promise a trial will help you personally — that is what the research is trying to find out.
What participation involves
Not stated in the study description — ask the study team about visits and procedures.
- Compensation
- Mentioned in the study description
- Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
- Participants are monitored closely by the research team throughout the study.
- Some participants may receive access to an investigational treatment, which is still being studied.
- Your participation helps researchers learn whether this approach could help future patients.
About this study
In plain language
This study tests two medicines taken by mouth, tetrahydrouridine and decitabine, for advanced myeloproliferative neoplasms (MPN), a group of blood cancers. It looks at how safe the treatment is, how well it works, and whether it is practical to use. It is for adults with certain advanced MPNs or myelofibrosis, a disease that scars the bone marrow.
This is a phase II, multicenter, open-label study evaluating the feasibility, safety, and efficacy of oral tetrahydrouridine-decitabine (THU-decitabine) in patients with advanced myeloproliferative neoplasms (MPN).
Compensation is read from the study's own description and may be missing — always confirm with the study team.
Eligibility
Who can join
- You must be at least 18 years old and weigh at least 41 kilograms (about 90 pounds).
- You must have an MPN with at least 10% blasts (immature blood cells) in your blood or bone marrow and a history of myelofibrosis, polycythemia vera, or essential thrombocythemia. Or, you may have chronic-phase myelofibrosis with 4–9% blasts in your blood.
- You must be able to care for yourself and be up and about for at least half of your waking hours.
- You may take a JAK inhibitor, a medicine used for MPN. Its dose must be stable for at least 4 weeks before starting the study.
- You must be able to swallow the medicine and follow the study visit schedule and rules.
- Your liver and kidney tests must meet study limits. Some liver test exceptions are allowed for Gilbert’s syndrome or blood cells forming outside the bone marrow because of myelofibrosis.
- Women who can become pregnant and men must use birth control before and during the study and for 6 months after treatment. Women need negative blood pregnancy tests at screening and on the first treatment day. Men must use condoms and must not father a child or donate sperm during treatment or for 6 months afterward.
- If you have another illness or cancer, it must not be expected to limit your life to 2 years or less.
Who can't join
- You cannot take venetoclax or join another treatment trial at the same time. Recent myelofibrosis drugs are also not allowed, except hydroxyurea and JAK inhibitors. The waiting period is 2 weeks or 5.5 drug half-lives (how long the drug takes to leave your body), whichever is shorter. You cannot have had more than 2 cycles of a hypomethylating drug given into a vein or under the skin.
- You cannot join if you are willing and able to receive a donor stem cell transplant right away without first needing treatment to lower your blood cell counts.
- You cannot have an uncontrolled illness that could affect your safety or study participation. Examples include active infection, uncontrolled cancer, severe heart failure, unstable chest pain or heartbeat, severe liver scarring, or mental health or social problems that prevent you from following study rules. Controlled heart failure or heartbeat problems may be allowed.
- You cannot have had a blood stem cell transplant within 100 days before treatment, be taking immune-suppressing drugs after that transplant at screening, or have used calcineurin inhibitors within 4 weeks before treatment. Significant graft-versus-host disease (donor cells attacking your body) is not allowed. Skin disease treated with steroid creams or less than 20 mg of oral prednisone may be allowed.
- You cannot have stomach or bowel problems that greatly affect how your body absorbs the medicine, including ongoing nausea, vomiting, or diarrhea above the study’s severity limit.
- You cannot join if you or an immediate family member works directly on this trial for the study site or sponsor, unless the ethics review board approves an exception.
- You cannot have had major surgery within 28 days before treatment or have surgery planned. You cannot have received an organ transplant other than a bone marrow transplant.
- You cannot be pregnant or breastfeeding.
Simplified for readability. The official criteria below are what the study team uses.
Official eligibility criteria
Inclusion Criteria: * Adults ≥ 18 years of age * Diagnosis of one of the following: * Accelerated-phase (≥ 10% blasts in PB or BM) or blast-phase (≥ 20% blasts in PB or BM) myeloproliferative neoplasm with a history of prior myelofibrosis, polycythemia vera, or essential thrombocythemia; or * Chronic phase myelofibrosis with 4-9% circulating blasts * Eastern Cooperative Oncology Group (ECOG) 0-2 * Concurrent use of physician's choice JAK1/2 inhibitors is permitted. Patients must be on stable dose of JAK2i for at least 4 weeks prior to starting the clinical trial. * Body weight ≥ 41 kg * Ability to swallow oral medication * Adequate organ function as demonstrated by all of the following: * ALT (SGPT) and/or AST (SGOT) \< 3x upper limit of normal (ULN), unless, upon judgment of the treating physician, it is believed to be due to MF-related extramedullary hematopoiesis (EMH) * Direct bilirubin \< 2 x ULN; unless it is believed to be due to MF-related EMH or documented/suspected Gilbert's syndrome; * Creatinine clearance ≥ 40 mL/min * Women of childbearing potential (WCBP) and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 6 months following completion of therapy. WCBP must also have a negative serum pregnancy test at screening and Cycle 1 Day 1. Should a woman become pregnant or suspect she is pregnant while participating, she should inform her treating physician immediately. Men must agree to use a condom and not father a child or donate sperm for the duration of the study and for 6 months after the last dose of study therapy * Ability to adhere to the study visit schedule and all protocol requirements * If the patient has co-morbid illness or malignancy, life expectancy attributed to this must be greater than 2 years. Exclusion Criteria: * Concurrent treatment with venetoclax * Treatment with any MF-directed drug treatments (including investigational therapies; excluding hydroxyurea and JAK inhibitor) within 2 weeks or 5.5 half-lives, whichever is shorter, of Cycle 1 Day 1 * Prior treatment with more than 2 cycles of prior IV or subcutaneous (SC) hypomethylating agent * Patients willing and able to undergo allogeneic stem cell transplant immediately without need for cytoreduction * Uncontrolled intercurrent illness that could limit life expectancy or ability to complete study correlates, including, but not limited to: * Ongoing or active infection * Uncontrolled concurrent other malignancy * Congestive heart failure of New York Heart Association (NYHA) class III/IV. Patients with compensated heart failure are permitted. * Unstable angina pectoris * New or unstable cardiac arrhythmia. Stable or controlled arrhythmias are permitted * Decompensated liver cirrhosis (Child-Pugh score ≥12 or a MELD score ≥21) * Psychiatric illness/social situations that would limit compliance with study requirements. * Any other prior or ongoing condition, in the opinion of the investigator, that could adversely affect the safety of the patient or impair the assessment of study results. * Hematopoietic cell transplant (HCT) within 100 days of the first dose of study therapy, receipt of immunosuppressive therapy post-HCT at screening, use of calcineurin inhibitors within 4 weeks prior to first dose of study therapy, or clinically significant GVHD * Note: The use of topical steroids or \< 20mg oral prednisone for ongoing skin GVHD is permitted * Impairment of gastrointestinal (GI) function or GI disease that could significantly alter the absorption of oral THU-Dec, including any unresolved nausea, vomiting, or diarrhea \> NCI CTCAE grade 2 * Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is investigational site or sponsor staff directly involved with this trial, unless prospective IRB approval (by chair or designee) is given allowing exception to this criterion for a specific subject * History of major surgery within 28 days prior to Cycle 1 Day 1 or any planned surgical procedures 10. * Organ transplant recipients other than bone marrow transplant * Women who are pregnant or lactating\\ * Concurrent enrollment in another interventional trial
Study sites (1)
NY
- Icahn School of Medicine at Mount Sinai · New York, NY 10029Gillian Sanchez · Study contact · gillian.sanchez@mssm.eduGabriela Bello · Study contact · gabriela.bello@mssm.eduJohn Mascarenhas · Principal investigatorMore trials in New York