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

NCT07228624 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: RG1125655NCI-2025-07728FHIRB0020989
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Myelodysplastic/Myeloproliferative Neoplasm; Primary Myelofibrosis; Secondary Myelofibrosis

Outcome Measures

Primary Outcomes (1)

• 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%.

  Up to day-100

Secondary Outcomes (9)

• Incidence of grade III-IV acute GVHD

  Up to day-100

• Incidence of any-grade chronic GVHD

  Up to 1 and 2 years

• Incidence of moderate-to-severe chronic GVHD

  Up to 1 and 2 years

• Non-relapse mortality (NRM)

  At day-100

• NRM

  At 1 year

Study Arms (1)

Treatment (ruxolitinib)

EXPERIMENTAL

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.

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

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Given infusion

Also known as: Allogeneic Hematopoietic Cell Transplantation, HSC, HSCT, Stem Cell Transplantation, Allogeneic

Treatment (ruxolitinib)

Computed Tomography PROCEDURE

Undergo CT

Also known as: 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

Treatment (ruxolitinib)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-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

Treatment (ruxolitinib)

Echocardiography Test PROCEDURE

Undergo echocardiography

Also known as: EC, Echocardiography

Treatment (ruxolitinib)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (ruxolitinib)

JAK Inhibitor DRUG

Given JAK inhibitor

Also known as: JAK inhibitors, Janus Kinase Inhibitor

Treatment (ruxolitinib)

Melphalan DRUG

Given IV

Also known as: 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

Treatment (ruxolitinib)

Methotrexate DRUG

Given IV

Also known as: 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

Treatment (ruxolitinib)

Tacrolimus DRUG

Given IV or PO

Also known as: FK 506, FK-506, FK506, Fujimycin, Hecoria, Prograf, Protopic, Tacforius

Treatment (ruxolitinib)

Biospecimen Collection PROCEDURE

Undergo urine and blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (ruxolitinib)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow biopsy and aspiration

Treatment (ruxolitinib)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy and aspiration

Also known as: Biopsy of Bone Marrow

Treatment (ruxolitinib)

Ruxolitinib DRUG

Given PO

Also known as: INCB 018424, INCB-018424, INCB-18424, INCB18424, Oral JAK Inhibitor INCB18424

Treatment (ruxolitinib)

Busulfan DRUG

Given IV

Also known as: 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

Treatment (ruxolitinib)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• Incyte Corporation: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Conditions

Myelodysplastic-Myeloproliferative Diseases; Primary Myelofibrosis

Interventions

ruxolitinib; Stem Cell Transplantation; Busulfan; Cyclophosphamide; fludarabine; Janus Kinase Inhibitors; Melphalan; Methotrexate; merphos; Tacrolimus; Specimen Handling

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Macrolides; Lactones; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Rachel Salit, MD

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rachel Salit, MD

CONTACT

206-667-1317; rsalit@fredhutch.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2025
• First Posted: November 14, 2025
• Study Start: February 4, 2026
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): September 1, 2030
• Last Updated: February 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)