Primary MyelofibrosisPhase 2NCT04370301
Reduced Intensity Haploidentical Transplantation for the Treatment of Primary or Secondary Myelofibrosis
A Phase 2 study testing Cyclophosphamide, JAK Inhibitor and Fludarabine in people with Primary Myelofibrosis and Secondary Myelofibrosis, run by Fred Hutchinson Cancer Center at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Primary Myelofibrosis, Secondary Myelofibrosis
- What is being tested?
- Cyclophosphamide, JAK Inhibitor and Fludarabine
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Feb 2021to 31 Aug 2029
- Phase
- Phase 2
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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- PART 1: JAK INHIBITOR ADMINISTRATION 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
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- PART 2: ALLOGENEIC STEM CELL TRANSPLANT INCLUSION CRITERIA
- 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
Who cannot join
- PART 1: JAK INHIBITOR ADMINISTRATION 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
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- 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)
- PART 2: ALLOGENEIC STEM CELL TRANSPLANT EXCLUSION CRITERIA
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109
Rachel B. Salit, 206-667-1317, rsalit@fredhutch.org
Rachel B. Salit
About this study
Official title: Pilot Study of JAK Inhibitor Therapy Followed by Reduced Intensity Haploidentical Transplantation for Patients With Myelofibrosis
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.
Read the detailed description
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
- Primary Myelofibrosis, Secondary Myelofibrosis
- Being tested
- Cyclophosphamide, JAK Inhibitor, Fludarabine, Recombinant Granulocyte Colony-Stimulating Factor, Melphalan
- Medical subject headings
- Primary Myelofibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida
Given IV
JAK InhibitorDrug
Also called JAK inhibitors, Janus Kinase Inhibitor, Ruxolitinib, Fedratinib
Given PO
FludarabineDrug
Also called Fluradosa
Given IV
Recombinant Granulocyte Colony-Stimulating FactorBiological
Also called Recombinant Colony-Stimulating Factor 3, rhG-CSF, 143011-72-7
Given SC
MelphalanDrug
Also called Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine mustard
Given IV
Also called Cellcept, MMF
Given PO
Peripheral Blood Stem Cell TransplantationProcedure or surgery
Also called PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, peripheral stem cell support
Given IV
TacrolimusDrug
Also called FK 506, Fujimycin, Hecoria, Prograf
Given IV and PO
Total-Body IrradiationRadiation
Also called TBI, Total Body Irradiation, Whole Body Irradiation, Whole-Body Irradiation
Undergo TBI
Computed TomographyProcedure or surgery
Also called CAT Scan, Computed Axial Tomography, CT SCAN
Undergo CT
Magnetic Resonance ImagingProcedure or surgery
Also called MR Imaging, MRI
Undergo MRI
Bone Marrow BiopsyProcedure or surgery
Also called Biopsy of Bone Marrow
Undergo bone marrow biopsy and aspiration
Bone Marrow AspirationProcedure or surgery
Undergo bone marrow biopsy and aspiration
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection
Undergo blood sample collection
Echocardiography TestProcedure or surgery
Also called EC
Undergo ECHO
Multigated Acquisition ScanProcedure or surgery
Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan
Undergo MUGA
| Study group | Role | What they receive |
|---|---|---|
| Cohort I (JAK inhibitor, conditioning, GVHD prophylaxis) | Experimental | 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. Receives: Drug: Cyclophosphamide; Drug: JAK Inhibitor; Drug: Fludarabine; Biological: Recombinant Granulocyte Colony-Stimulating Factor; Drug: Melphalan; Drug: Mycophenolate Mofetil; Procedure: Peripheral Blood Stem Cell Transplantation; Drug: Tacrolimus; Radiation: Total-Body Irradiation; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Bone Marrow Biopsy; Procedure: Bone Marrow Aspiration; Procedure: Biospecimen Collection; Procedure: Echocardiography Test; Procedure: Multigated Acquisition Scan |
| Cohort II (JAK inhibitor, conditioning, GVHD prophylaxis) | Experimental | 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. Receives: Drug: Cyclophosphamide; Drug: JAK Inhibitor; Drug: Fludarabine; Biological: Recombinant Granulocyte Colony-Stimulating Factor; Drug: Melphalan; Drug: Mycophenolate Mofetil; Procedure: Peripheral Blood Stem Cell Transplantation; Drug: Tacrolimus; Radiation: Total-Body Irradiation; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Bone Marrow Biopsy; Procedure: Bone Marrow Aspiration; Procedure: Biospecimen Collection; Procedure: Echocardiography Test; Procedure: Multigated Acquisition Scan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Probability of primary and secondary graft failure
Primary graft failure is defined as failure to achieve an absolute neutrophil count of > 500/ul by 42 days after bone marrow or peripheral blood stem cell transplantation. Secondary graft failure is defined as cytopenias after initial engraftment, with (a) donor chimerism of < 5% or (b) falling donor chimerism with intervention such as second transplant or donor lymphocyte infusion or (c) patient death due to cytopenias, and fall in donor chimerism, even if chimerism is > 5%. Exclusion criteria for diagnosis of graft failure are (a) disease relapse, (b) graft-versus-host disease, and (c) other causes of cytopenias such as, viral infection and drug toxicity.
Measured: Up to 5 years
Secondary outcomes (9)
Incidence of severe (grade 3 or 4) cytokine release syndrome
Measured: Up to 5 years
Non-relapse mortality (NRM)
Measured: Day 100
NRM
Measured: 1 year
Overall survival
Measured: 1 year
Overall survival
Measured: 3 years
Incidence of grade II-IV acute graft versus host disease (GVHD)
Measured: Up to 5 years
Incidence of grade III-IV acute GVHD
Measured: Up to 5 years
Incidence of moderate-severe chronic GVHD
Measured: Up to 5 years
Incidence of relapse
Measured: At 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2020
- Study start9 Feb 2021
- Primary completion30 Apr 2027 (estimated)
- Study completion31 Aug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary MyelofibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fred Hutchinson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rachel B. Salit, Principal investigator, Fred Hutch/University of Washington Cancer Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04370301
- Sponsor's protocol ID
- RG1006957
- Other IDs
- NCI-2020-02422, 10441
- Status last verified
- Jul 2026
- First submitted
- 28 Apr 2020
- Last updated
- 20 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No