Reduced Intensity Haploidentical Transplantation for the Treatment of Primary or Secondary Myelofibrosis

NCT ID: NCT04370301

Last Updated: 2026-01-12

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

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-02-09

Study Completion Date

2029-08-31

Brief Summary

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This initial cohort of this phase II trial studied the outcomes of using a JAK inhibitor prior to reduced intensity haploidentical (Haplo) transplantation for the treatment of primary or secondary myelofibrosis (MF). The primary risk of using Haplo HCT in patients with MF is graft failure. In the first cohort, all patients engrafted. There were no instances of graft failure. However, a large number of patients did have graft versus host disease as a complication of their transplant. JAK inhibitors have since been approved for the indication of graft versus host disease treatment. And we are also using them for graft versus host disease prevention in a study of MF patients with sibling and unrelated donors. Therefore, we are opening a new cohort of the current study using the JAK inhibitor prior to, during and after Haplo transplant. Our goal is to decrease graft versus host disease in patients receiving a Haplo MF transplant without increasing the risk of graft failure.

Detailed Description

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OUTLINE: Cohort 1 is now closed and all patients will be enrolled on Cohort 2.

COHORT I:

JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of hematopoietic cell transplantation (HCT) conditioning through day -4 before transplantation.

CONDITIONING: Patients receive melphalan intravenously (IV) over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo total-body irradiation (TBI) on day -1 or day -1 and day 0.

TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.

GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then orally (PO) for about 6 months, mycophenolate mofetil PO twice daily (BID) or three times daily (TID) beginning day 5 for 6 weeks, and granulocyte colony-stimulating factor (G-CSF) subcutaneously (SC) beginning day 7 until neutrophil recovery is \> 1,500/mm\^3.

COHORT II:

JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation. Additionally, patients receive a JAK inhibitor following transplantation beginning day +5 through 9-12 months after transplant.

CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.

TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.

GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is \> 1,500/mm\^3.

All patients undergo magnetic resonance imaging (MRI), computed tomography (CT), bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) on the trial.

After completion of study treatment, patients are followed up between day 80-100, at 1 year, and then up to 5 years.

Conditions

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Primary Myelofibrosis Secondary Myelofibrosis

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort I (JAK inhibitor, conditioning, GVHD prophylaxis)

JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation.

CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.

TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.

GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is \> 1,500/mm\^3.

All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.

Group Type EXPERIMENTAL

Cyclophosphamide

Intervention Type DRUG

Given IV

JAK Inhibitor

Intervention Type DRUG

Given PO

Fludarabine

Intervention Type DRUG

Given IV

Recombinant Granulocyte Colony-Stimulating Factor

Intervention Type BIOLOGICAL

Given SC

Melphalan

Intervention Type DRUG

Given IV

Mycophenolate Mofetil

Intervention Type DRUG

Given PO

Peripheral Blood Stem Cell Transplantation

Intervention Type PROCEDURE

Given IV

Tacrolimus

Intervention Type DRUG

Given IV and PO

Total-Body Irradiation

Intervention Type RADIATION

Undergo TBI

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Bone Marrow Biopsy

Intervention Type PROCEDURE

Undergo bone marrow biopsy and aspiration

Bone Marrow Aspiration

Intervention Type PROCEDURE

Undergo bone marrow biopsy and aspiration

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Echocardiography Test

Intervention Type PROCEDURE

Undergo ECHO

Multigated Acquisition Scan

Intervention Type PROCEDURE

Undergo MUGA

Cohort II (JAK inhibitor, conditioning, GVHD prophylaxis)

JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation. Additionally, patients receive a JAK inhibitor following transplantation beginning day 5 through 9-12 months after transplant.

CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.

TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.

GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is \> 1,500/mm\^3.

All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.

Group Type EXPERIMENTAL

Cyclophosphamide

Intervention Type DRUG

Given IV

JAK Inhibitor

Intervention Type DRUG

Given PO

Fludarabine

Intervention Type DRUG

Given IV

Recombinant Granulocyte Colony-Stimulating Factor

Intervention Type BIOLOGICAL

Given SC

Melphalan

Intervention Type DRUG

Given IV

Mycophenolate Mofetil

Intervention Type DRUG

Given PO

Peripheral Blood Stem Cell Transplantation

Intervention Type PROCEDURE

Given IV

Tacrolimus

Intervention Type DRUG

Given IV and PO

Total-Body Irradiation

Intervention Type RADIATION

Undergo TBI

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Bone Marrow Biopsy

Intervention Type PROCEDURE

Undergo bone marrow biopsy and aspiration

Bone Marrow Aspiration

Intervention Type PROCEDURE

Undergo bone marrow biopsy and aspiration

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Echocardiography Test

Intervention Type PROCEDURE

Undergo ECHO

Multigated Acquisition Scan

Intervention Type PROCEDURE

Undergo MUGA

Interventions

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Cyclophosphamide

Given IV

Intervention Type DRUG

JAK Inhibitor

Given PO

Intervention Type DRUG

Fludarabine

Given IV

Intervention Type DRUG

Recombinant Granulocyte Colony-Stimulating Factor

Given SC

Intervention Type BIOLOGICAL

Melphalan

Given IV

Intervention Type DRUG

Mycophenolate Mofetil

Given PO

Intervention Type DRUG

Peripheral Blood Stem Cell Transplantation

Given IV

Intervention Type PROCEDURE

Tacrolimus

Given IV and PO

Intervention Type DRUG

Total-Body Irradiation

Undergo TBI

Intervention Type RADIATION

Computed Tomography

Undergo CT

Intervention Type PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

Intervention Type PROCEDURE

Bone Marrow Biopsy

Undergo bone marrow biopsy and aspiration

Intervention Type PROCEDURE

Bone Marrow Aspiration

Undergo bone marrow biopsy and aspiration

Intervention Type PROCEDURE

Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Echocardiography Test

Undergo ECHO

Intervention Type PROCEDURE

Multigated Acquisition Scan

Undergo MUGA

Intervention Type PROCEDURE

Other Intervention Names

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(-)-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 Asta B 518 B-518 WR-138719 JAK inhibitors Janus Kinase Inhibitor Ruxolitinib Fedratinib Fluradosa Recombinant Colony-Stimulating Factor 3 rhG-CSF 143011-72-7 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 Cellcept MMF PBPC transplantation PBSCT Peripheral Blood Progenitor Cell Transplantation peripheral stem cell support Peripheral Stem Cell Transplant peripheral stem cell transplantation FK 506 Fujimycin Hecoria Prograf Protopic FK-506 Tacforius TBI Total Body Irradiation Whole Body Irradiation Whole-Body Irradiation Total-Body Irradiation Prior to Stem Cell Transplant SCT_TBI CAT Scan Computed Axial Tomography CT SCAN MR Imaging MRI Biopsy of Bone Marrow Biological Sample Collection EC Blood Pool Scan Equilibrium Radionuclide Angiography Gated Blood Pool Imaging Gated Heart Pool Scan MUGA MUGA Scan Multi-Gated Acquisition Scan Radionuclide Ventriculogram Scan RNVG SYMA Scanning Synchronized Multigated Acquisition Scanning

Eligibility Criteria

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Inclusion Criteria

* Age between 18 and 70 years
* Diagnosis of primary myelofibrosis (PMF) as defined by the 2016 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)-plus scoring system (DIPSS may be used if all data from DIPSS are not available)
* Ability to understand and the willingness to sign a written informed consent document (or legally authorized representative)
* Patient must be a potential hematopoietic stem cell transplant candidate
* 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 (or legally authorized representative). 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
* Received JAK inhibitor for at least 8 weeks immediately prior to conditioning and be willing to continue until 9-12 months post-transplant as tolerated
* Karnofsky performance status score \>= 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 \> 3 mg/dL, and symptomatic biliary disease will be excluded
* Diffusion capacity of the lung for carbon monoxide (DLCO) corrected \> 60% normal; may not be on supplemental oxygen
* Left ventricular ejection fraction \> 40% OR shortening fraction \> 26%
* Comorbidity Index \< 5 at the time of pre-transplant evaluation
* DONOR: Patients must be screened prior to transplant for donor-specific anti-HLA antibodies (DSA). Patients with DSA will be reviewed by the principal investigator and considered for desensitization treatment
* DONOR: Children are preferred over siblings and parents
* DONOR: Younger donors are preferred over older donors
* DONOR: ABO matched donors are preferred over minor ABO mismatched and over major ABO mismatch donors

Exclusion Criteria

* Contraindication to receiving a JAK inhibitor 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 study enrollment
* Active or recent (prior 6 month) invasive fungal infection without infectious disease (ID) consult and approval
* Known HIV positivity
* Pregnant or breastfeeding
* Availability of an human leukocyte antigen (HLA)-identical or 1-allele-mismatched related donor or an HLA 10 of 10 matched unrelated donor
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fred Hutchinson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Rachel B. Salit

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 B. Salit

Role: CONTACT

206-667-1317

Facility Contacts

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Rachel B. Salit

Role: primary

206-667-1317

Other Identifiers

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NCI-2020-02422

Identifier Type: REGISTRY

Identifier Source: secondary_id

10441

Identifier Type: OTHER

Identifier Source: secondary_id

RG1006957

Identifier Type: -

Identifier Source: org_study_id

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