Peritransplant Ruxolitinib for Patients With Primary and Secondary Myelofibrosis

NCT04384692 | Active Not Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: RG1006507NCI-2020-0162610093
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Primary Myelofibrosis; Secondary Myelofibrosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Incidence of grade III-IV GVHD

  Up to day 100

• Incidence of chronic GVHD

  At 1 and 2 years

• Overall survival rate (OS)

  At 1 and 2 years

• Incidence of primary and secondary graft failure

  6 months

• Time to neutrophil (ANC > 500) engraftment

  Day 100

Study Arms (1)

Treatment (ruxolitinib, conditioning, HSCT, GVHD prophylaxis)

EXPERIMENTAL

See detailed description.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Busulfan; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Melphalan; Drug: Methotrexate; Drug: Mycophenolate Mofetil; Drug: Ruxolitinib; Drug: Tacrolimus; Radiation: Total-Body Irradiation; Procedure: Computed Tomography; Procedure: Echocardiography; Procedure: Bone Marrow Aspiration and Biopsy; Procedure: Magnetic Resonance Imaging; Procedure: Ultrasound Imaging

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo HSCT

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

Treatment (ruxolitinib, conditioning, HSCT, GVHD prophylaxis)

Busulfan DRUG

Given IV

Also known as: 1, 4-Bis[methanesulfonoxy]butane, BUS, 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, conditioning, HSCT, GVHD prophylaxis)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, 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

Treatment (ruxolitinib, conditioning, HSCT, GVHD prophylaxis)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (ruxolitinib, conditioning, HSCT, GVHD prophylaxis)

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, Melphalanum, Phenylalanine Mustard, Phenylalanine Nitrogen Mustard, Sarcoclorin, Sarkolysin, WR-19813

Treatment (ruxolitinib, conditioning, HSCT, GVHD prophylaxis)

Methotrexate DRUG

Given IV

Also known as: Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate, CL 14377, CL-14377, Emtexate, Emthexat, Emthexate, Farmitrexat, Fauldexato, Folex, Folex PFS, 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, Jylamvo

Treatment (ruxolitinib, conditioning, HSCT, GVHD prophylaxis)

Mycophenolate Mofetil DRUG

Given IV or PO

Also known as: CellCept, MMF

Treatment (ruxolitinib, conditioning, HSCT, GVHD prophylaxis)

Ruxolitinib DRUG

Given PO

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

Treatment (ruxolitinib, conditioning, HSCT, GVHD prophylaxis)

Tacrolimus DRUG

Given IV and PO

Also known as: FK 506, Fujimycin, Hecoria, Prograf, Protopic

Treatment (ruxolitinib, conditioning, HSCT, GVHD prophylaxis)

Total-Body Irradiation RADIATION

Undergo TBI

Also known as: TBI, Total Body Irradiation, Whole Body Irradiation, Whole-Body Irradiation, Total-Body Irradiation Prior to Stem Cell Transplant

Treatment (ruxolitinib, conditioning, HSCT, GVHD prophylaxis)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT Scan, Computed Axial Tomography

Treatment (ruxolitinib, conditioning, HSCT, GVHD prophylaxis)

Echocardiography PROCEDURE

Undergo echocardiography

Also known as: EC

Treatment (ruxolitinib, conditioning, HSCT, GVHD prophylaxis)

Bone Marrow Aspiration and Biopsy PROCEDURE

Undergo bone marrow aspiration and biopsy

Treatment (ruxolitinib, conditioning, HSCT, GVHD prophylaxis)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: MRI

Treatment (ruxolitinib, conditioning, HSCT, GVHD prophylaxis)

Ultrasound Imaging PROCEDURE

Undergo ultrasound imaging

Also known as: 2-Dimensional Grayscale Ultrasound Imaging

Treatment (ruxolitinib, conditioning, HSCT, GVHD prophylaxis)

Eligibility Criteria

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

You may qualify if:

• Age \>= 18 years
• 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
• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

Stem Cell Transplantation; Busulfan; Cyclophosphamide; fludarabine; Melphalan; Methotrexate; merphos; Mycophenolic Acid; ruxolitinib; Tacrolimus; Whole-Body Irradiation; Biopsy; Magnetic Resonance Spectroscopy; High-Energy Shock Waves

Condition Hierarchy (Ancestors)

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

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; 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; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Macrolides; Lactones; Radiotherapy; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Spectrum Analysis; Chemistry Techniques, Analytical; Ultrasonic Waves; Sound; Radiation, Nonionizing; Radiation; Physical Phenomena

Study Officials

• Rachel B. Salit

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

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: May 8, 2020
• First Posted: May 12, 2020
• Study Start: December 18, 2020
• Primary Completion: April 3, 2026
• Study Completion (Estimated): April 23, 2030
• Last Updated: April 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)