Peritransplant Ruxolitinib for Patients With Primary and Secondary Myelofibrosis

This phase II trial studies how well administering ruxolitinib before, during, and after allogeneic hematopoietic stem cell transplantation works in preventing graft versus host disease and improving transplant outcomes in patients with primary and secondary myelofibrosis. Donor hematopoietic stem cell transplantation (HSCT) is currently the only treatment with proven curative potential for myelofibrosis, however, myelofibrosis patients have a high risk for developing graft versus host disease post-transplant. Graft versus host disease is a condition where the transplanted cells from a donor can attack the body's normal cells. Ruxolitinib, a janus-associated kinase (JAK) inhibitor, is known to decrease inflammatory signals, which may reduce spleen size and decrease symptoms such as night sweats and weight loss. Administering ruxolitinib before, during, and after transplant may decrease the incidence and severity of graft versus host disease, increase survival, and improve quality of life in patients with primary and secondary myelofibrosis.

Study Overview

• Status: Active, not recruiting
• Conditions: Primary Myelofibrosis; Secondary Myelofibrosis
• Intervention / Treatment: Procedure: Magnetic Resonance Imaging; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Methotrexate; Procedure: Computed Tomography; Drug: Melphalan; Drug: Tacrolimus; Radiation: Total-Body Irradiation; Procedure: Bone Marrow Aspiration and Biopsy; Drug: Busulfan; Drug: Ruxolitinib; Drug: Mycophenolate Mofetil; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Procedure: Ultrasound Imaging; Procedure: Echocardiography

Detailed Description

OUTLINE:

PART 1: Patients receive ruxolitinib orally (PO) starting 8 weeks prior to hematopoietic stem cell transplantation (HSCT) and continuing until approximately 14 days prior to conditioning regimen, then tapered per the treating clinician until day -4 in the absence of disease progression or unacceptable toxicity. Patients who join a different research study for Part 2 have their collected data and samples from Part 1 carried over to the new protocol.

PART 2: Patients are assigned to either a high (myeloablative) or reduced intensity conditioning regimens per the clinical provider together with the Clinical Coordinators Office (CCO):

MYELOABLATIVE CONDITIONING: Patients receive cyclophosphamide intravenously (IV) on days -7 and -6 and busulfan IV over 3 hours on days -5 to -2. Patients with umbilical cord blood (UCB) as their transplant source also receive fludarabine IV over 30 minutes on days -8 to -6. Treatment continues in the absence of disease progression or unacceptable toxicity.

REDUCED INTENSITY CONDITIONING: Patients receive fludarabine IV over 30 minutes on days -6 to -2 and melphalan IV over 15-30 minutes on days -3 and -2. Patients with UCB as their transplant source also undergo total body irradiation (TBI) on day -1. Treatment continues in the absence of disease progression or unacceptable toxicity.

TRANSPLANT: After completion of conditioning regimen, patients undergo HSCT on day 0.

GVHD PROPHYLAXIS: Patients receive ruxolitinib until approximately 7 months post-transplant and then tapered over 2 months until 9-12 months post HSCT. Patients also receive tacrolimus IV continuously (inpatients) or every 12 hours (outpatients) beginning day -1 (day -3 for patients with UCB as their donor source), then PO twice daily (BID) once therapeutic levels are reached, with a taper beginning on day 56 for patients with related donors, and day 100 for patients with unrelated donors over 4 months in the absence of GVHD. The duration of tacrolimus for patients with GVHD is determined by the attending physician. Patients with related and unrelated donors also receive methotrexate IV on days 1, 3, 6, and 11. Patients with UCB as their transplant source also receive mycophenolate mofetil IV or PO every 8 hours beginning on days 0-30, then tapered until day 40 in the absence of GVHD. All treatment continues in the absence of disease progression or unacceptable toxicity.

Patients undergo computed tomography (CT) scan and may undergo echocardiography on study and bone marrow aspiration and biopsy and blood sample collection and may undergo magneti resonance imaging (MRI) and ultrasound throughout the study.

Patients are followed up at 6 months, 1 year, and 2-5 years after completion of HSCT.

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutch/University of Washington Cancer Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age >= 18 years
• JAK INHIBITOR ADMINISTRATION INCLUSION: (PART I)

• Disease criteria:

  • Diagnosis of primary myelofibrosis (PMF) as defined by the 2016 World Health Organization classification system or diagnosis of secondary myelofibrosis (MF) as defined by the International Working Group (IWG) for Myeloproliferative Neoplasms Research and Treatment criteria
  • Patients meeting the criteria for intermediate-1, intermediate-2 or high-risk disease by Dynamic International Prognostic Scoring System (DIPSS) or DIPSS plus
• Ability to understand and the willingness to sign a written informed consent document
• Patient must be a potential hematopoietic stem cell transplant candidate as assessed by the consenting physician
• Patient must be willing to start ruxolitinib within a 6-month time period
• ALLOGENEIC STEM CELL TRANSPLANT INCLUSION: (PART II)
• Meeting criteria for part 1, as above, at time of initiation of ruxolitinib, including the ability to understand and willingness to sign a written informed consent. Patients arriving to our institution for transplant 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 medical records
• Received ruxolitinib for at least 8 weeks immediately prior to conditioning and be willing to continue until 9-12 months post-transplant as tolerated
• Performance status score: Karnofsky >= 70
• Calculated creatinine clearance using the Cockcroft-Gault formula or 24 hour (hr) urine creatinine clearance must be > 60 ml/min
• Total serum bilirubin must be < 3 mg/dL unless the elevation is thought to be due to Gilbert's disease or hemolysis
• Transaminases must be < 3 x the upper limit of normal
• 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
• Diffusion capacity of lung for carbon monoxide (DLCO) corrected > 60% normal. May be not be on supplemental oxygen
• Left ventricular ejection fraction > 40% OR shortening fraction > 26%
• Comorbidity index < 5 at the time of pre-transplant evaluation

Exclusion Criteria:

• JAK INHIBITOR ADMINISTRATION EXCLUSION: (PART I)

• Contraindication to receiving ruxolitinib including:

  • Patients who have known hypersensitivity to JAK inhibitors
  • Clinical or laboratory evidence of significant renal or hepatic impairment including cirrhosis
  • Active uncontrolled infection
  • Known human immunodeficiency virus (HIV) positivity
  • Women who are pregnant or trying to conceive
  • Caution should be used in patients with platelets < 100 though adjustments in dose can be made to accommodate anyone with platelets > 50
• History of prior allogeneic transplant
• Leukemic transformation (> 20% blasts)
• ALLOGENEIC STEM CELL TRANSPLANT EXCLUSION: (PART II)
• Uncontrolled viral or bacterial infection at the time of transplant data review and consent conference
• Active or recent (prior 6 month) invasive fungal infection without infectious disease (ID) consult and approval
• History of HIV infection
• Pregnant or breastfeeding
• Patients without a human leukocyte antigen (HLA)-identical sibling donor, 10 of 10 HLA-matched or 9 of 10 allele mismatched unrelated donor, or umbilical cord blood units that meet transplant criteria

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (ruxolitinib, conditioning, HSCT, GVHD prophylaxis); See detailed description.

Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Drug: Cyclophosphamide; Given IV; Other Names: Cytoxan; CTX; (-)-Cyclophosphamide; 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate; Carloxan; Ciclofosfamida; Ciclofosfamide; Cicloxal; Clafen; Claphene; CP monohydrate; CYCLO-cell; Cycloblastin; Cycloblastine; Cyclophospham; Cyclophosphamid monohydrate; Cyclophosphamide Monohydrate; Cyclophosphamidum; Cyclophosphan; Cyclophosphane; Cyclophosphanum; Cyclostin; Cyclostine; Cytophosphan; Cytophosphane; Fosfaseron; Genoxal; Genuxal; Ledoxina; Mitoxan; Neosar; Revimmune; Syklofosfamid; WR- 138719; Drug: Fludarabine; Given IV; Other Names: Fluradosa; Drug: Methotrexate; Given IV; Other Names: Abitrexate; Folex; Mexate; MTX; Alpha-Methopterin; Amethopterin; Brimexate; CL 14377; CL-14377; Emtexate; Emthexat; Emthexate; Farmitrexat; Fauldexato; Folex PFS; Lantarel; Ledertrexate; Lumexon; Maxtrex; Medsatrexate; Metex; Methoblastin; Methotrexate LPF; Methotrexate Methylaminopterin; Methotrexatum; Metotrexato; Metrotex; Mexate-AQ; Novatrex; Rheumatrex; Texate; Tremetex; Trexeron; Trixilem; WR-19039; Jylamvo; Procedure: Computed Tomography; Undergo CT scan; Other Names: CAT Scan; Computed Axial Tomography; Drug: Melphalan; Given IV; Other Names: CB-3025; L-PAM; L-Sarcolysin; Alanine Nitrogen Mustard; L-Phenylalanine Mustard; L-Sarcolysin Phenylalanine mustard; L-Sarcolysine; Melphalanum; Phenylalanine Mustard; Phenylalanine Nitrogen Mustard; Sarcoclorin; Sarkolysin; WR-19813; Drug: Tacrolimus; Given IV and PO; Other Names: Prograf; Hecoria; FK 506; Fujimycin; Protopic; Radiation: Total-Body Irradiation; Undergo TBI; Other Names: Total Body Irradiation; TBI; Whole Body Irradiation; Whole-Body Irradiation; Total-Body Irradiation Prior to Stem Cell Transplant; Procedure: Bone Marrow Aspiration and Biopsy; Undergo bone marrow aspiration and biopsy; Drug: Busulfan; Given IV; Other Names: Busulfex; Misulfan; Mitosan; Myeloleukon; Myelosan; 1, 4-Bis[methanesulfonoxy]butane; BUS; Bussulfam; Busulfanum; Busulphan; CB 2041; CB-2041; Glyzophrol; GT 41; GT-41; Joacamine; Methanesulfonic Acid Tetramethylene Ester; Methanesulfonic acid, tetramethylene ester; Mielucin; Misulban; Myeleukon; Mylecytan; Myleran; Sulfabutin; Tetramethylene Bis(methanesulfonate); Tetramethylene bis[methanesulfonate]; WR-19508; Drug: Ruxolitinib; Given PO; Other Names: INCB-18424; INCB18424; Oral JAK Inhibitor INCB18424; Drug: Mycophenolate Mofetil; Given IV or PO; Other Names: CellCept; MMF; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Undergo HSCT; Other Names: Allogeneic Hematopoietic Cell Transplantation; Allogeneic Stem Cell Transplantation; HSC; HSCT; Stem Cell Transplantation, Allogeneic; Procedure: Ultrasound Imaging; Undergo ultrasound imaging; Other Names: 2-Dimensional Grayscale Ultrasound Imaging; Procedure: Echocardiography; Undergo echocardiography; Other Names: EC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of grade II-IV graft versus host disease (GVHD) in myelofibrosis patients	The probability of grade II-IV acute GVHD observed in this study will be compared to a fixed benchmark, this fixed benchmark derived from the results of a previous study (FH Protocol 9033).	Up to day 100

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of relapse		At 1 year
Incidence of grade III-IV GVHD	Estimated as simple proportions and informally compared to the results from FH Protocol 9033.	Up to day 100
Overall survival rate (OS)		At 1 and 2 years
Incidence of primary and secondary graft failure	Estimated as simple proportions and informally compared to the results from FH Protocol 9033.	6 months
Time to neutrophil (ANC > 500) engraftment		Day 100
Time to platelet (> 20,000) engraftment		Day 100
Non-relapse mortality (NRM)	Estimated as simple proportions and informally compared to the results from FH Protocol 9033.	Day 100 and 1 year
Incidence of chronic GVHD		At 1 and 2 years

Collaborators and Investigators

• Sponsor: Fred Hutchinson Cancer Center
• Investigators: Principal Investigator: Rachel B. Salit, Fred Hutch/University of Washington Cancer Consortium

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2020
• Primary Completion (Actual): April 3, 2026
• Study Completion (Estimated): April 23, 2030

Study Registration Dates

• First Submitted: May 8, 2020
• First Submitted That Met QC Criteria: May 8, 2020
• First Posted (Actual): May 12, 2020

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 10, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Bone Marrow Diseases; Myeloproliferative Disorders; Hemic and Lymphatic Diseases; Primary Myelofibrosis; Amino Acids, Peptides, and Proteins; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Investigative Techniques; Therapeutics; Fatty Acids; Lipids; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Cytological Techniques; Cytodiagnosis; Hydrocarbons, Acyclic; Hydrocarbons; Physical Phenomena; Acids, Acyclic; Carboxylic Acids; Transplantation; Amino Acids; Alkanes; Diagnostic Techniques, Surgical; Alcohols; Chemistry Techniques, Analytical; Butylene Glycols; Glycols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Sulfonic Acids; Sulfur Acids; Macrolides; Lactones; Spectrum Analysis; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Pterins; Pteridines; Aminopterin; Radiotherapy; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Radiation; Radiation, Nonionizing; Caproates; Ultrasonic Waves; Sound; Methotrexate; Cyclophosphamide; Melphalan; Mycophenolic Acid; Tacrolimus; Busulfan; Biopsy; Magnetic Resonance Spectroscopy; fludarabine; Stem Cell Transplantation; ruxolitinib; Whole-Body Irradiation; merphos; High-Energy Shock Waves
• Other Study ID Numbers: RG1006507; 10093 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium); NCI-2020-01626 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No