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Primary MyelofibrosisPhase 2NCT02251821

JAK Inhibitor Before Donor Stem Cell Transplant in Treating Patients With Primary or Secondary Myelofibrosis

A Phase 2 study testing Allogeneic Hematopoietic Stem Cell Transplantation, Busulfan and Cyclophosphamide in people with Primary Myelofibrosis and Secondary Myelofibrosis, run by Fred Hutchinson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase II trial studies how well giving a JAK inhibitor before a donor stem cell transplant works in treating patients with myelofibrosis that developed without another condition (primary) or evolved from other bone marrow disorders (secondary). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Allogeneic Hematopoietic Stem Cell Transplantation, Busulfan and Cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
61 participants
Where
1 siteUnited States
Study dates
20 Oct 2014to 22 Jan 2026
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • PART 1:
  • PART 1: Disease criteria
  • Diagnosis of primary MF (PMF) as defined by the 2008 World Health Organization classification system or diagnosis of secondary 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 the Dynamic International Prognostic Scoring System (DIPSS) or DIPSS-plus scoring system
  • PART 1: Ability to understand and the willingness to sign a written informed consent document
  • PART 1: Patient must be a potential hematopoietic stem cell transplant candidate
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  • PART 2:
  • PART 2: Meeting criteria for 1st phase as above, at time of initiation of JAK inhibitor, including 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 met; these patients will have Part 1 endpoints transcribed from medical records
  • PART 2: Received ruxolitinib for at least 8 weeks immediately prior to conditioning and be able to continue until Day -4 pre-transplant
  • PART 2: Performance status score
  • Karnofsky >= 70
  • PART 2: Calculated creatinine clearance using the Cockcroft-Gault formula or 24 hr urine creatinine clearance must be > 60 ml/min
  • PART 2: Total serum bilirubin must be < 3 mg/dL unless the elevation is thought to be due to Gilbert's disease or hemolysis
  • PART 2: Transaminases must be < 3 x the upper limit of normal
  • PART 2: 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 > 3 mg/dL, and symptomatic biliary disease will be excluded
  • PART 2: Diffusing capacity of the lung for carbon monoxide (DLCO) corrected > 60% normal
  • May not be on supplemental oxygen
  • PART 2: Left ventricular ejection fraction > 40% OR
  • PART 2: Shortening fraction > 26%
  • PART 2: Comorbidity Index < 5 at the time of pre-transplant evaluation
  • DONOR:
  • DONOR: Human leukocyte antigen (HLA)-matched or 1 antigen mismatched sibling donor
  • DONOR: 10 of 10 HLA-matched or 1 allele mismatched (9 of 10) unrelated donor
  • DONOR: Peripheral blood is preferred over bone marrow for non-umbilical cord blood recipients
  • DONOR: Umbilical cord blood units will be selected according to the following umbilical cord blood graft selection criteria; one or 2 cord blood (CB) units may be used to achieve the required cell dose
  • DONOR: The CB graft(s) must be matched at 4-6 HLA-A, B, DR Beta 1 (DRB1) loci with the recipient and therefore may include 0-2 mismatches at the A or B or DRB1 loci; unit selection will be based on cryopreserved nucleated cell dose and intermediate resolution A, B antigen and DRB1 allele typing for determination of HLA-match; while HLA-C antigen/allele level typing is not considered in the matching criteria, if available, it may be used to optimize unit selection
  • DONOR: Selection of two CB units is allowed to provide sufficient cell dose (see below for algorithm to determine single versus double unit transplant); when multiple units are selected, the following rules apply:
  • The CB unit with the least HLA disparity (with the patient) will be selected first (i.e., selection priority is 6/6 match > 5/6 match > 4/6 match); additional CB units then may be selected to achieve the required cell dose, as outlined below; if a second unit is required, this unit will be the unit that most closely HLA matches the patient and meets minimum size criteria outlined below of at least 1.5 x 10^7 total nucleated cells (TNC)/kg (i.e. a smaller, more closely matched unit will be selected over a larger, less well matched unit as long as minimum criteria are met)
  • If two CB units are used:
  • The total cell dose of the combined units must be at least 3.0 x 10^7 TNC per kilogram recipient weight
  • Each CB unit MUST contain at least 1.5 x 10^7 TNC per kilogram recipient weight
  • Algorithm for determining single versus double unit cord blood transplant:
  • Match grade 6/6: TNC dose >= 2.5 x 10^7/kg
  • Match grade 5/6, 4/6: TNC dose >= 4.0 (+/- 0.5) x 10^7/kg
  • DONOR: General comments:
  • Units will be selected first based on the TNC dose and HLA matching
  • Cluster of differentiation (CD)34+ cell dose will not be used for unit selection unless 2 units of equal HLA-match grade are available; in this case, the unit with the larger CD34+ cell dose (if data available) should be selected
  • A CB unit that is 5/6 mismatched but homozygous at the locus of mismatch should be chosen over a 5/6 unit with bidirectional mismatch even if the latter unit is larger (has more cells); this also applies to 4/6 units; this is only applicable to choosing units within a given match grade
  • Other factors to be considered:
  • Within the same HLA match grade, matching at DR takes preference
  • Cord blood banks located in the United States are preferred
  • Up to 5% of the cord blood product(s), when ready for infusion, may be withheld for research purposes as long as thresholds for infused TNC dose are met; these products will be used to conduct studies involving the kinetics of engraftment and immunobiology of double cord transplantation

Who cannot join

  • PART 1:
  • PART 1: Evidence of human immunodeficiency virus (HIV) infection or known HIV positive serology
  • PART 1: Uncontrolled viral, bacterial, or fungal infections at the time of study enrollment
  • PART 1: History of prior allogeneic transplant
  • PART 1: Pregnant or breastfeeding (only if patients have not been started on ruxolitinib [Rux] by their primary oncologist prior to enrollment)
  • PART 2:
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  • PART 2: Uncontrolled viral or bacterial infection at the time of study enrollment
  • PART 2: Active or recent (prior 6 month) invasive fungal infection without infectious disease (ID) consult and approval
  • PART 2: History of HIV infection
  • PART 2: Pregnant or breastfeeding
  • PART 2: Patients without an HLA-identical or 1-allele-mismatched related donor or unrelated donor or umbilical cord blood units that meet transplant criteria

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: JAK Inhibitor Prior to Allogeneic Stem Cell Transplant for Patients With Primary and Secondary Myelofibrosis: A Prospective Study

This phase II trial studies how well giving a JAK inhibitor before a donor stem cell transplant works in treating patients with myelofibrosis that developed without another condition (primary) or evolved from other bone marrow disorders (secondary). JAK inhibitors are a class of drugs that may stop the growth of abnormal cells by blocking an enzyme needed for cell growth. Giving a JAK inhibitor such as ruxolitinib before a donor stem cell transplant may help reduce symptoms of myelofibrosis such as inflammation and enlargement of the spleen, improve the patient's general physical condition, and prevent complications from occurring after the transplant. Infusing healthy stem cells from a donor into the patient may help the patient's bone marrow work normally and make stem cells, red blood cells, white blood cells, and platelets. Giving a JAK inhibitor before a donor stem cell transplant may help improve transplant outcomes in patients with myelofibrosis.

Read the detailed description

OUTLINE:

PART 1: Patients receive ruxolitinib orally (PO) twice daily (BID) from at least 8 weeks prior to the start of conditioning through day -4 before transplantation, with a taper schedule reducing the dose every 2-3 days beginning after day -4.

PART 2: Patients are assigned to 1 of 2 conditioning regimens at the discretion of the clinical provider and Clinical Coordinators Office (CCO).

MYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) over 1 hour on days -8 to -6 (umbilical cord blood transplant recipients only), cyclophosphamide IV on days -7 and -6, and busulfan IV over 3 hours on days -5 to -2.

REDUCED-INTENSITY CONDITIONING: Patients receive fludarabine phosphate IV over 1 hour on days -6 to -2 and melphalan IV over 15-30 minutes on days -3 and -2. Patients also undergo total-body irradiation (TBI) on day -1 (umbilical cord blood transplant recipients only).

TRANSPLANT: Patients undergo allogeneic hematopoietic stem cell transplant or umbilical cord blood transplant on day 0.

GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive tacrolimus IV continuously (inpatients) or over 1-2 hours twice daily (BID) (outpatients) or orally (PO) BID on days -1 to +180 (patients receiving related or unrelated stem cells) or days -3 to +180 (patients receiving umbilical cord blood) with taper beginning on day +56 (related donor recipients) or +100 (unrelated donor or umbilical cord blood recipients) in the absence of GVHD. Patients also receive methotrexate IV on days +1, +3, +6, and +11 (related and unrelated donor recipients only) or mycophenolate mofetil IV or PO every 8 hours on days 0 to +40 with taper to day +96 (umbilical cord blood transplant recipients only).

After completion of study treatment, patients are followed up at 6 months, 1 year, and then yearly for 4 years.

Medical subject headings
Primary Myelofibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery

    Also called Allogeneic Hematopoietic Cell Transplantation, allogeneic stem cell transplantation, HSC, HSCT

    Undergo allogeneic hematopoietic stem cell transplant

  • BusulfanDrug

    Also called 1, 4-Bis[methanesulfonoxy]butane, BUS, Bussulfam, Busulfanum

    Given IV

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • Fludarabine PhosphateDrug

    Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • 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

  • Mycophenolate MofetilDrug

    Also called Cellcept, MMF

    Given IV or PO

  • RuxolitinibDrug

    Also called INCB-18424, INCB18424, Oral JAK Inhibitor INCB18424, Jakafi

    Given PO

  • TacrolimusDrug

    Also called FK 506, Fujimycin, Hecoria, Prograf

    Given IV or PO

  • Total-Body IrradiationRadiation

    Also called TOTAL BODY IRRADIATION, Whole-Body Irradiation, SCT_TBI

    Undergo TBI

  • Umbilical Cord Blood TransplantationProcedure or surgery

    Also called Cord Blood Transplantation, UCB transplantation

    Undergo umbilical cord blood transplant

Study groups in NCT02251821
Study groupRoleWhat they receive
Treatment (ruxolitinib, transplant)ExperimentalPatients receive a ruxolitinib and undergo myeloablative or reduced-intensity conditioning followed by transplant and GVHD prophylaxis; see detailed description.
Receives: Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Busulfan; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Drug: Melphalan; Drug: Methotrexate; Drug: Mycophenolate Mofetil; Drug: Ruxolitinib; Drug: Tacrolimus; Radiation: Total-Body Irradiation; Procedure: Umbilical Cord Blood Transplantation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 2-year Overall Survival (OS) in Patients With Myelofibrosis (MF) Who Receive Treatment With a JAK Inhibitor Followed by an Allogeneic Transplant

    OS was defined as the time from date of transplantation to date of death due to any cause. In the absence of confirmation of death, survival time was censored to last date the participant was known to be alive. The 2-year survival probability was estimated using the Kaplan-Meier method and a 2-sided 95% confidence interval (CI).

    Measured: 2 years

Secondary outcomes (9)

  1. Percentage of Participants With Acute Graft Versus Host Disease (GVHD) Grade II-IV

    Percentage of Participants with Grade II-IV acute GVHD in the first 100 days post HCT.

    Measured: Up to 100 days post-transplant

  2. Percentage of Participants With Chronic Graft Versus Host Disease (GVHD)

    Max grade of chronic GVHD mild, moderate or severe at any time within the first 2 years following transplant.

    Measured: 2 years

  3. Percentage of Patients Who Had Relapsed Disease at 1 Year

    Patients who had evidence of residual disease by molecular, flow cytometric or cytogenetics/FISH were considered relapsed disease.

    Measured: 1 year

  4. Non-relapse Mortality (NRM)

    Patients who died in remission between day of transplant and day 100.

    Measured: Day 100

  5. Non-relapse Mortality (NRM)

    Measured: 1 year

  6. Number of Patients Who Experienced Primary Graft Failure/Rejection

    Patients who failed to achieve ANC > 500 x 3 or chimerism > 5% by day 42 post-transplant.

    Measured: Up to 42 days post-transplant

  7. Number of Patients Who Experienced Secondary Graft Failure/Poor Graft Function

    Patients who engrafted with an ANC >500 x 3 or chimerism > 5% and then became neutropenic with ANC <500x3 days or chimerism <5% without evidence of relapse.

    Measured: Up to 5 years

  8. Percentage of Patients With a Max Grade of Moderate and Severe Chronic GVHD at Any Time Before 2 Years Post Transplant.

    Includes patients who had a max grade of moderate or severe chronic GVHD by the NIH scoring system at any time between day 0 and 2 years post transplant.

    Measured: 2 years post-HCT

  9. Percentage of Participants With Acute Graft Versus Host Disease Grade III-IV GVHD

    Patients who had a max grade of III-IV acute GVHD any time between Day 0 and Day 100.

    Measured: 100 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Sep 2014 (estimated)
  2. Study start20 Oct 2014
  3. Primary completion28 Dec 2022
  4. Study completion22 Jan 2026

Resources

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
61 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02251821
Sponsor's protocol ID
9033
Other IDs
NCI-2014-01882, 9033, RG9214017, P30CA015704
Status last verified
Jan 2026
First submitted
12 Sep 2014
Last updated
30 Mar 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Allogeneic Hematopoietic Stem Cell Transplantation, Busulfan and Cyclophosphamide in people with Primary Myelofibrosis and Secondary Myelofibrosis, run by Fred Hutchinson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 42 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

2-year Overall Survival (OS) in Patients With Myelofibrosis (MF) Who Receive Treatment With a JAK Inhibitor Followed by an Allogeneic Transplant (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02251821.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2026.

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