Ruxolitinib Before, During and After Hematopoietic Cell Transplant in Older Patients With Myelofibrosis and Myelodysplastic Syndrome/Myeloproliferative Neoplasm Overlap Syndromes

NCT ID: NCT07228624

Last Updated: 2026-01-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-02-21

Study Completion Date

2030-09-01

Brief Summary

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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.

Detailed Description

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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) twice daily (BID) for 12 months then PO 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, chest computed tomography (CT) and pulmonary function testing prior to conditioning and blood sample collection, bone marrow biopsy and aspiration and 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

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Myelodysplastic/Myeloproliferative Neoplasm Primary Myelofibrosis Secondary Myelofibrosis

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (ruxolitinib)

PART 1: Patients receive ruxolitinib or alternate JAK-inhibitor for at least 8 weeks prior to the start of HCT conditioning.

PART 2: Starting on day -4, patients receive ruxolitinib 5mg PO BID for 12 months then PO 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.

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, and pulmonary function testing prior to conditioning and blood sample collection, bone marrow biopsy and aspiration, and spleen ultrasound or CT throughout the study.

Group Type EXPERIMENTAL

Ruxolitinib

Intervention Type DRUG

Given PO

Allogeneic Hematopoietic Stem Cell Transplantation

Intervention Type PROCEDURE

Given infusion

Busulfan

Intervention Type DRUG

Given IV

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Cyclophosphamide

Intervention Type DRUG

Given IV

Echocardiography Test

Intervention Type PROCEDURE

Undergo echocardiography

Fludarabine

Intervention Type DRUG

Given IV

JAK Inhibitor

Intervention Type DRUG

Given JAK inhibitor

Melphalan

Intervention Type DRUG

Given IV

Methotrexate

Intervention Type DRUG

Given IV

Tacrolimus

Intervention Type DRUG

Given IV or PO

Biospecimen Collection

Intervention Type PROCEDURE

Undergo urine and blood sample collection

Bone Marrow Aspiration

Intervention Type PROCEDURE

Undergo bone marrow biopsy and aspiration

Bone Marrow Biopsy

Intervention Type PROCEDURE

Undergo bone marrow biopsy and aspiration

Interventions

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Ruxolitinib

Given PO

Intervention Type DRUG

Allogeneic Hematopoietic Stem Cell Transplantation

Given infusion

Intervention Type PROCEDURE

Busulfan

Given IV

Intervention Type DRUG

Computed Tomography

Undergo CT

Intervention Type PROCEDURE

Cyclophosphamide

Given IV

Intervention Type DRUG

Echocardiography Test

Undergo echocardiography

Intervention Type PROCEDURE

Fludarabine

Given IV

Intervention Type DRUG

JAK Inhibitor

Given JAK inhibitor

Intervention Type DRUG

Melphalan

Given IV

Intervention Type DRUG

Methotrexate

Given IV

Intervention Type DRUG

Tacrolimus

Given IV or PO

Intervention Type DRUG

Biospecimen Collection

Undergo urine and blood sample collection

Intervention Type PROCEDURE

Bone Marrow Aspiration

Undergo bone marrow biopsy and aspiration

Intervention Type PROCEDURE

Bone Marrow Biopsy

Undergo bone marrow biopsy and aspiration

Intervention Type PROCEDURE

Other Intervention Names

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INCB 018424 INCB-018424 INCB-18424 INCB18424 Oral JAK Inhibitor INCB18424 Allogeneic Hematopoietic Cell Transplantation HSC HSCT Stem Cell Transplantation, Allogeneic 1, 4-Bis[methanesulfonoxy]butane BUS Busilvex Bussulfam Busulfanum Busulfex Busulphan CB 2041 CB-2041 Glyzophrol GT 41 GT-41 Joacamine Methanesulfonic Acid Tetramethylene Ester Methanesulfonic acid, tetramethylene ester Mielucin Misulban Misulfan Mitosan Myeleukon Myeloleukon Myelosan Mylecytan Myleran Sulfabutin Tetramethylene Bis(methanesulfonate) Tetramethylene bis[methanesulfonate] WR-19508 CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography Computerized Tomography (CT) scan CT CT Scan Diagnostic CAT Scan Diagnostic CAT Scan Service Type tomography (-)-Cyclophosphamide 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate Asta B 518 B 518 B-518 B518 Carloxan Ciclofosfamida Ciclofosfamide Cicloxal Clafen Claphene CP monohydrate CTX CYCLO-cell Cycloblastin Cycloblastine Cyclophospham Cyclophosphamid monohydrate Cyclophosphamide Monohydrate Cyclophosphamidum Cyclophosphan Cyclophosphane Cyclophosphanum Cyclostin Cyclostine Cytophosphan Cytophosphane Cytoxan Fosfaseron Genoxal Genuxal Ledoxina Mitoxan Neosar Revimmune Syklofosfamid WR 138719 WR- 138719 WR-138719 WR138719 EC Echocardiography Fluradosa JAK inhibitors Janus Kinase Inhibitor Alanine Nitrogen Mustard CB-3025 L-PAM L-Phenylalanine Mustard L-Sarcolysin L-Sarcolysin Phenylalanine mustard L-Sarcolysine Melphalan for Injection-Hepatic Delivery System Melphalanum Phenylalanine Mustard Phenylalanine Nitrogen Mustard Sarcoclorin Sarkolysin WR-19813 Abitrexate Alpha-Methopterin Amethopterin Brimexate CL 14377 CL-14377 Emtexate Emthexat Emthexate Farmitrexat Fauldexato Folex Folex PFS Jylamvo Lantarel Ledertrexate Lumexon Maxtrex Medsatrexate Metex Methoblastin Methotrexate LPF Methotrexate Methylaminopterin Methotrexatum Metotrexato Metrotex Mexate Mexate-AQ MTX Novatrex Rheumatrex Texate Tremetex Trexeron Trixilem WR-19039 FK 506 FK-506 FK506 Fujimycin Hecoria Prograf Protopic Tacforius Biological Sample Collection Biospecimen Collected Specimen Collection Biopsy of Bone Marrow

Eligibility Criteria

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Inclusion Criteria

* 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
* 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: 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

Exclusion Criteria

* 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)
* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Incyte Corporation

INDUSTRY

Sponsor Role collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Rachel Salit, MD

Role: PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Locations

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Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Rachel Salit, MD

Role: CONTACT

206-667-1317

Facility Contacts

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Rachel Salit, MD

Role: primary

206-667-1317

Other Identifiers

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NCI-2025-07728

Identifier Type: REGISTRY

Identifier Source: secondary_id

FHIRB0020989

Identifier Type: OTHER

Identifier Source: secondary_id

RG1125655

Identifier Type: -

Identifier Source: org_study_id

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