Myelodysplastic/Myeloproliferative NeoplasmPhase 2NCT07228624
Ruxolitinib Before, During and After Hematopoietic Cell Transplant in Older Patients With Myelofibrosis and Myelodysplastic Syndrome/Myeloproliferative Neoplasm Overlap Syndromes
A Phase 2 study testing Ruxolitinib, Allogeneic Hematopoietic Stem Cell Transplantation and Busulfan in people with Myelodysplastic/Myeloproliferative Neoplasm and Primary Myelofibrosis, run by Fred Hutchinson Cancer Center at 1 site in United States.
Trial summary
This phase II trial tests the effect of adding ruxolitinib to standard graft versus host disease (GVHD) prevention in treating older patients with myelofibrosis (MF) or myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) overlap syndromes before, during, and after a donor (allogeneic) hematopoietic cell… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Myelodysplastic/Myeloproliferative Neoplasm, Primary Myelofibrosis, Secondary Myelofibrosis
- What is being tested?
- Ruxolitinib, Allogeneic Hematopoietic Stem Cell Transplantation and Busulfan
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Feb 2026to 1 Sep 2030
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- PART 1 JAK INHIBITOR ADMINISTRATION: Age 18-75 years
- Patients > 75 must be considered an HCT candidate, meet all protocol criteria and have comorbidity score =< 3 and Karnofsky performance status (KPS) > or = to 90. Patients. > 75 who do not meet these criteria may be presented at PCC for consensus exception
- PART 1 JAK INHIBITOR ADMINISTRATION: Disease criteria
- Diagnosis of primary or secondary MF as defined by the 2022 World Health Organization classification system or the International Consensus Classification for Myeloid and Acute Leukemias
- Diagnosis of an MDS/MPN overlap syndrome as defined by the 2022 World Health Organization
- PART 1 JAK INHIBITOR ADMINISTRATION: Ability to understand and the willingness to sign a written informed consent document
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- PART 1 JAK INHIBITOR ADMINISTRATION: Patient must be a potential HCT candidate as assessed by the consenting physician
- PART 1 JAK INHIBITOR ADMINISTRATION: Patient must be agreeable to taking a JAK-inhibitor (ruxolitinib preferred) for at least 8 consecutive weeks immediately prior to conditioning and be willing to take ruxolitinib 5mg BID starting from day -4 prior to and continuing until 12 months post-transplant as tolerated followed by a 6-month taper.
- PART 2 ALLOGENEIC STEM CELL TRANSPLANT: Meeting criteria for Part 1 at time of initiation of JAK-inhibitor, including the ability to understand and willingness to sign a written informed consent. Patients arriving to our institution for HCT and not enrolled in Part 1 may still be enrolled in Part 2 if Part 1 criteria are met. These patients will have Part 1 endpoints transcribed from their medical records
- PART 2 ALLOGENEIC STEM CELL TRANSPLANT: Received a JAK-inhibitor for at least 8 weeks immediately prior to conditioning and be willing to take Rux from day -4 at the 5mg BID dose until 12 months post-transplant as tolerated followed by a 6 month taper
- PART 2 ALLOGENEIC STEM CELL TRANSPLANT: Performance status score
- Karnofsky ≥ 70 or > 90 for patients > 75 years old
- PART 2 ALLOGENEIC STEM CELL TRANSPLANT: HCT-CI Score < 8; if patient is > 75 years old HCT-CI < 3
- PART 2 ALLOGENEIC STEM CELL TRANSPLANT: Calculated creatinine clearance using the Cockcroft-Gault formula or 24-hour urine creatinine clearance must be > 60 ml/min
- PART 2 ALLOGENEIC STEM CELL TRANSPLANT: Total serum bilirubin must be < 3mg/dL unless the elevation is thought to be due to Gilbert's disease or hemolysis
- PART 2 ALLOGENEIC STEM CELL TRANSPLANT: Transaminases must be < 3 x the upper limit of normal
- PART 2 ALLOGENEIC STEM CELL TRANSPLANT: Patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension. Patients with fulminant liver failure, cirrhosis with evidence of portal hypertension or bridging fibrosis, alcoholic hepatitis, hepatic encephalopathy, or correctable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3mg/dL, and symptomatic biliary disease will be excluded
- PART 2 ALLOGENEIC STEM CELL TRANSPLANT: Diffusion capacity of lung for carbon monoxide (DLCO) corrected > 60% normal. Patient may not be on oxygen
- PART 2 ALLOGENEIC STEM CELL TRANSPLANT: Left ventricular ejection fraction > 40%
- DONOR: Human leukocyte antigen (HLA)-matched sibling donor
- DONOR: 10 of 10 HLA-matched unrelated donor
- DONOR: 9 of 10 allele or antigen mismatched unrelated donor
- DONOR: Peripheral blood is preferred over bone marrow
- DONOR: ABO matched donors should be selected if possible
- DONOR: Matched unrelated donors may be preferred over siblings if the unrelated donor is < 30 years and the sibling is > 60 years. However, sibling donors < 70 should be preferred over mismatched unrelated donors
Who cannot join
- PART 1 JAK INHIBITOR ADMINISTRATION: Contraindication to receiving ruxolitinib including patients who have known hypersensitivity to JAK inhibitors and excipients
- PART 1 JAK INHIBITOR ADMINISTRATION: History of prior allogeneic transplant
- PART 1 JAK INHIBITOR ADMINISTRATION: Leukemic transformation (> 20% blasts)
- PART 1 JAK INHIBITOR ADMINISTRATION: Uncontrolled viral, bacterial, or fungal infection despite being on therapy
- PART 1 JAK INHIBITOR ADMINISTRATION: History of HIV infection
- PART 1 JAK INHIBITOR ADMINISTRATION: History of untreated tuberculosis (TB)
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- PART 1 JAK INHIBITOR ADMINISTRATION: Pregnant or breastfeeding
- PART 1 JAK INHIBITOR ADMINISTRATION: Patients with history of myocardial infarction (MI), cerebrovascular accident (CVA) or unprovoked pulmonary embolism (PE)/deep vein thrombosis (DVT) in the past 6 months
- PART 1 JAK INHIBITOR ADMINISTRATION: Secondary malignancy in last 5 years with > 20% risk of relapse
- PART 2 ALLOGENEIC STEM CELL TRANSPLANT: Contraindication to receiving ruxolitinib including patients who have known hypersensitivity to JAK inhibitors and excipients
- PART 2 ALLOGENEIC STEM CELL TRANSPLANT: History of prior allogeneic transplant
- PART 2 ALLOGENEIC STEM CELL TRANSPLANT: Leukemic transformation (> 20% blasts)
- PART 2 ALLOGENEIC STEM CELL TRANSPLANT: Uncontrolled viral or bacterial infection at the time of transplant data review and consent conference
- PART 2 ALLOGENEIC STEM CELL TRANSPLANT: Active or recent (prior 6 month) invasive fungal infection without infectious disease (ID) consult and approval
- PART 2 ALLOGENEIC STEM CELL TRANSPLANT: History of HIV infection
- PART 2 ALLOGENEIC STEM CELL TRANSPLANT: History of untreated TB
- PART 2 ALLOGENEIC STEM CELL TRANSPLANT: Requiring supplemental oxygen
- PART 2 ALLOGENEIC STEM CELL TRANSPLANT: Pregnant or breastfeeding
- PART 2 ALLOGENEIC STEM CELL TRANSPLANT: Secondary malignancy in last 5 years with > 20% risk of relapse
- PART 2 ALLOGENEIC STEM CELL TRANSPLANT: Patients with a history of MI, CVA, or unprovoked PE/DVT in the past 6 months
- PART 2 ALLOGENEIC STEM CELL TRANSPLANT: Patients without an HLA-identical sibling donor, 10 of 10 HLA-matched or 9 of 10 mismatched unrelated donor
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109
Rachel Salit, MD, 206-667-1317, rsalit@fredhutch.org
Rachel Salit, MD
About this study
Official title: Peri-Hematopoietic Cell Transplantation Ruxolitinib in Patients With Myelofibrosis and Myelodysplastic Syndrome/Myeloproliferative Neoplasm Overlap Syndromes
This phase II trial tests the effect of adding ruxolitinib to standard graft versus host disease (GVHD) prevention in treating older patients with myelofibrosis (MF) or myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) overlap syndromes before, during, and after a donor (allogeneic) hematopoietic cell transplant (HCT). Allogeneic HCT is a procedure in which a person receives blood-forming stem cells (cells from which all blood cells develop) from a genetically similar, but not identical donor. Giving chemotherapy, such as cytoxan and busulfan or fludarabine and melphalan, before a donor transplant helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. However, sometimes the transplanted cells from a donor can attack the body's normal cells (called GVHD). Giving standard prevention (prophylaxis) therapies, such as tacrolimus and methotrexate, after the transplant may stop this from happening. Methotrexate, a type of antifolate, is in a class of medications called antimetabolites. Methotrexate stops cells from using folic acid to make deoxyribonucleic acid and may kill cancer cells. Tacrolimus is used to help reduce the risk of rejection by the body of organ and bone marrow transplants. Ruxolitinib, a type of Janus-associated kinase (JAK) inhibitor, blocks a protein called JAK, which may help keep abnormal blood cells or cancer cells from growing. It may also lower the body's immune response and prevent the development of GVHD. Giving ruxolitinib before, during and after allogeneic HCT in addition to standard GVHD prophylaxis may be safe, tolerable and effective in preventing GVHD and improving outcomes in older patients with MF or MDS/MPN overlap syndrome.
Read the detailed description
OUTLINE:
PART 1: Patients receive ruxolitinib or an alternate JAK-inhibitor for at least 8 weeks prior to the start of HCT conditioning. Starting on day -4, patients receive 5 mg of ruxolitinib orally (PO) or via nasogastric tube twice daily (BID) for 12 months then PO via nasogastric tube once daily (QD) until 18 months. Patients receive high intensity conditioning with cyclophosphamide intravenously (IV) on days -7 and -6 and busulfan IV over 3 hours on days -5 to -2 or reduced intensity conditioning with fludarabine IV over 30 minutes on days -6 to -2 and melphalan IV over 15-30 minutes on days -3 and -2.
PART 2: Patients receive stem cells infusion on day 0. Starting on day -3, patients receive tacrolimus IV over 1-2 hours or PO every 12 hours for at least 100 days. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
Additionally, patients undergo urine sample collection, echocardiography (ECHO), chest computed tomography (CT) and pulmonary function testing prior to conditioning and blood sample collection throughout the study. Patients may also undergo bone marrow biopsy and aspiration, and/or spleen ultrasound or CT at multiple time points before and after transplant.
After completion of study treatment, patients are followed at days 28, 100, 180, and at 9 months, 1 year, 18 months and 2 years.
- Conditions
- Myelodysplastic/Myeloproliferative Neoplasm, Primary Myelofibrosis, Secondary Myelofibrosis
- Being tested
- Ruxolitinib, Allogeneic Hematopoietic Stem Cell Transplantation, Busulfan, Computed Tomography, Cyclophosphamide
- Medical subject headings
- Myelodysplastic-Myeloproliferative Diseases, Primary Myelofibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RuxolitinibDrug
Also called INCB 018424, INCB-018424, INCB-18424, INCB18424
Given PO or via nasogastric tube
Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery
Also called Allogeneic Hematopoietic Cell Transplantation, HSC, HSCT, Stem Cell Transplantation, Allogeneic
Given infusion
BusulfanDrug
Also called 1, 4-Bis[methanesulfonoxy]butane, BUS, Busilvex, Bussulfam
Given IV
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518
Given IV
Echocardiography TestProcedure or surgery
Also called EC, Echocardiography
Undergo echocardiography
FludarabineDrug
Also called Fluradosa
Given IV
JAK InhibitorDrug
Also called JAK inhibitors, Janus Kinase Inhibitor
Given JAK inhibitor
MelphalanDrug
Also called Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard
Given IV
MethotrexateDrug
Also called Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate
Given IV
TacrolimusDrug
Also called FK 506, FK-506, FK506, Fujimycin
Given IV or PO
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo urine and blood sample collection
Bone Marrow AspirationProcedure or surgery
Undergo bone marrow biopsy and aspiration
Bone Marrow BiopsyProcedure or surgery
Also called Biopsy of Bone Marrow
Undergo bone marrow biopsy and aspiration
| Study group | Role | What they receive |
|---|---|---|
| Treatment (ruxolitinib) | Experimental | PART 1: Patients receive ruxolitinib or alternate JAK-inhibitor for at least 8 weeks prior to the start of HCT conditioning.
Starting on day -4, patients receive ruxolitinib 5mg PO or via nasogastric tube BID for 12 months then PO via nasogastric tube QD until 18 months. Patients receive high intensity conditioning with cyclophosphamide IV on days -7 and -6 and busulfan IV over 3 hours on days -5 to -2 or reduced intensity conditioning with fludarabine IV over 30 minutes on days -6 to -2 and melphalan IV over 15-30 minutes on days -3 and -2.
PART 2: Patients receive stem cells infusion on day 0. Starting on day -3, patients receive tacrolimus IV over 1-2 hours or PO every 12 hours for at least 100 days. Patients also receive methotrexate IV on days 1, 3, 6, and 11. Receives: Drug: Ruxolitinib; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Busulfan; Procedure: Computed Tomography; Drug: Cyclophosphamide; Procedure: Echocardiography Test; Drug: Fludarabine; Drug: JAK Inhibitor; Drug: Melphalan; Drug: Methotrexate; Drug: Tacrolimus; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of grade II-IV graft versus host disease (GVHD) requiring systemic immune suppression
Will be estimated as a simple proportion, and the upper bound of the one-sided 95% confidence interval for the estimated proportion will be estimated using the Clopper-Pearson method. The exact binomial test will be used to compare the observed probability to the benchmark of 65%.
Measured: Up to day-100
Secondary outcomes (9)
Incidence of grade III-IV acute GVHD
Will be estimated as simple proportions and informally compared to the results from the historical cohort.
Measured: Up to day-100
Incidence of any-grade chronic GVHD
Will be treated as time-to-event endpoints, with specified point estimates.
Measured: Up to 1 and 2 years
Incidence of moderate-to-severe chronic GVHD
Will be treated as time-to-event endpoints, with specified point estimates.
Measured: Up to 1 and 2 years
Non-relapse mortality (NRM)
Will be estimated as simple proportions and informally compared to the results from the historical cohort.
Measured: At day-100
NRM
Will be treated as time-to-event endpoints, with specified point estimates.
Measured: At 1 year
Remission status
Will be estimated as simple proportions and informally compared to the results from the historical cohort.
Measured: At day-100
Relapse rate
Will be treated as time-to-event endpoints, with specified point estimates.
Measured: At 1 and 2 years
Overall survival
Will be treated as time-to-event endpoints, with specified point estimates.
Measured: Up to 1 year and by end of study, assessed up to 2 years
Incidence of graft failure
Will be estimated as simple proportions and informally compared to the results from the historical cohort.
Measured: Up to day-100
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2025
- Study start4 Feb 2026
- Primary completion1 Sep 2030 (estimated)
- Study completion1 Sep 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelodysplastic/Myeloproliferative NeoplasmStudies 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
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fred Hutchinson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Incyte Corporation
- Responsible party
- Sponsor
- Investigators
- Rachel Salit, MD, Principal investigator, Fred Hutch/University of Washington Cancer Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07228624
- Sponsor's protocol ID
- RG1125655
- Other IDs
- NCI-2025-07728, FHIRB0020989
- Status last verified
- Oct 2026
- First submitted
- 13 Nov 2025
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No