MyelofibrosisPhase 2MPN-RC 127NCT07872709
Oral Tetrahydrouridine-Decitabine in Patients With Advanced Myeloproliferative Neoplasms
A Phase 2 study testing Oral THU-decitabine in people with Myelofibrosis and MPN - Accelerated or Blast Phase, run by John Mascarenhas at 1 site in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelofibrosis, MPN - Accelerated or Blast Phase, Chric Phase MPN
- What is being tested?
- Oral THU-decitabine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2027to Jan 2033
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 15Show fewer
- 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.
Who cannot join
- 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
Show all 21Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Shakira Forde contact
United States1 site
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Gillian Sanchez, gillian.sanchez@mssm.edu
Gabriela Bello, gabriela.bello@mssm.edu
About this study
Official title: An Open-Label, Phase II Study Evaluating the Feasibility, Safety, and Efficacy of Oral Tetrahydrouridine-Decitabine in Patients With Advanced Myeloproliferative Neoplasms
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).
Read the detailed description
This is a phase 2, multicenter trial evaluating the feasibility of administering oral THU-Dec with or without JAK2 inhibitor in patients with advanced MPNs. Eligible subjects will receive oral THU-Dec orally once weekly on a four week (28 day) cycle for a core study period of 6 cycles (24 weeks). The primary endpoint will be assessed after 6 cycles of treatment. Feasibility will be assessed as the treatment completion rate, defined as the proportion of patients who receive ≥75% of planned THU-Decitabine doses for at least 6 cycles or who discontinue treatment to receive allogeneic hematopoietic stem cell transplantation. After 24 weeks, subjects who demonstrate any response as per modified Cheson Criteria or stable disease may continue to receive treatment until loss of response, disease progression, unacceptable toxicity, subject/physician withdrawal, or the study is terminated.
- Being tested
- Oral THU-decitabine
- Medical subject headings
- Primary Myelofibrosis, Blast Crisis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral THU-decitabineDrug
Combination of Tetrahydrouridine and Decitabine oral treatment. Treatment is ingested weekly without interruption. For convenience of communication and planning, 4 weeks of treatment (28 days) is considered a treatment cycle. The first 2 cycles of therapy (week 1-8 of therapy) is considered an induction phase. After the induction phase (Cycle 3+): Treatment continues weekly.
| Study group | Role | What they receive |
|---|---|---|
| Oral THU-decitabine | Experimental | Study participants will receive oral THU-decitabine once weekly (on the same day each week ±1 day). Oral THU-Dec 8-12/0.16-0.24 mg/kg (~10/0.2 mg/kg) (THU ingested 1 hour before decitabine). THU and decitabine are supplied as capsules: each THU capsule contains THU 250 mg; each decitabine capsule contains decitabine 5 mg. Since this trial utilizes capsules, there has to be rounding of dosages. Receives: Drug: Oral THU-decitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment Completion Rate
Proportion of patients who receive ≥75% of planned THU-Dec doses for at least 6 cycles (24 weeks) OR discontinue treatment to receive allogeneic hematopoietic stem cell transplantation
Measured: 6 Cycles (24 Weeks)
Secondary outcomes (12)
Overall Survival
The median overall survival of advanced phase MPN patients treated with oral THU-Dec ± JAK2i
Measured: 48 Months
Complete Blast Response
No circulating blasts in peripheral blood and less than 5% in bone marrow.
Measured: 48 Months
Partial Blast Response
A 50% reduction in peripheral blood or bone marrow blasts.
Measured: 48 Months
Chronic Phase BF Blast
The proportion of treated patients with chronic phase MF and 4%-9% circulating blasts that achieve a response (complete response, partial response, clinical improvement, anemia, spleen, symptom response, cytogenetic or molecular remission).
Measured: 6 Cycles (24 Weeks)
MFSAF TSS
Change in MPN-SAF TSS from baseline after 6 and 12 cycles; symptom response will be determined in participants with baseline MPN-SAF TSS ≥ 10. Symptom improvement response is defined as a number of participants with improvement in symptoms response as defined by Myeloproliferative Neoplasms Symptoms Assessment Form (MPN-SAF). The MPN-SAF is a questionnaire that measures certain symptoms and how they improve throughout the study, from baseline. The questionnaire is divided into 4 sections - 1: 16 questions about the most common symptoms in these disease types, rated from 0 (lowest impact) to 10 (biggest impact); 2: Highest grade of fever; 3: Unintentional weight loss; 4. Quality of life, rated from 0 (as good as it can be) to 10 (as bad as it can be). MPN-SAF is an 18-item instrument. Each item score 0-10 averaged, total scale from 0-10, with higher score indicating more symptoms.
Measured: 48 Months
EORTC-QLC-30
This is a 30-question tool used to assess the overall QoL in cancer participants. It consisted of 15 domains: 1 GHS/QoL scale, 5 functional scales (Physical, role, cognitive, emotional, social), and 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact). Most items are scored 1 ("not at all") to 4 ("very much") except for the items contributing to the GHS/QoL, which are scored 1 ("very poor") to 7 ("excellent"). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100. For the GHS/QoL and 5 functional scales a high score indicates better global health status/functioning and a negative change from baseline indicated less improvement. For the symptom scales, a high score indicates a higher level of symptoms, and a negative change from baseline indicated an improvement in symptoms.
Measured: 48 Months
PGIC Score
The Patient's Global Impression of Change (PGIC) will be used to assess self-reported relieving effect. It will evaluate pain from no change (score 0-1), minimally improved (score 2-3), much improved (score 4-5), and very much improved (score 6-7). The patients will answer the following question: "Since beginning treatment at this program, how would you describe the change (if any) in activity limitations, symptoms, emotions, and overall quality of life related to your condition?". Full score from 0-7, with higher score indicating more improvement. Change in score at Week 2, Week 10 and Week 14 as compared to Baseline.
Measured: 48 Months
Allogeneic Stem Cell Transplant
Rate of allogeneic stem cell transplant occurrence among those participating in the study.
Measured: 48 Months
Time to Treatment Failure (TTF)
TTF is defined as time from enrollment to discontinuation of treatment for any reason.
Measured: 48 Months
Dose Delays
Frequency of THU-Dec dose delays
Measured: 48 Months
Dose Interruptions
Frequency of THU-Dec dose interruptions
Measured: 48 Months
Rate of Hospitalization
Rate of hospitalizations related to complications of treatment or disease.
Measured: 48 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2026
- Study startJan 2027 (estimated)
- Primary completionJul 2029 (estimated)
- Study completionJan 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MyelofibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- John Mascarenhas
- Sponsor type
- University, hospital or other
- Collaborators
- Treebough Therapies, National Cancer Institute (NCI)
- Responsible party
- Sponsor-investigator, John Mascarenhas, Icahn School of Medicine at Mount Sinai
- Investigators
- John Mascarenhas, MD, Study director, Icahn School of Medicine at Mount SinaiMarina Kremyanskaya, MD, PhD, Study chair, Icahn School of Medicine at Mount SinaiShivani V Handa, MD, Study chair, Ohio State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07872709
- Sponsor's protocol ID
- STUDY-26-00886
- Other IDs
- 5P01CA108671
- Acronym
- MPN-RC 127
- Status last verified
- Oct 2026
- First submitted
- 7 Oct 2026
- Last updated
- 14 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: The completed dataset is the sole property of the Sponsor-Investigator's institution and should not be exported to third parties, except for authorized representatives of appropriate Health/Regulatory Authorities, without permission from the Sponsor-investigator and their institution.