Recruiting
Phase 2

Haploidentical Transplantation

Sponsor:

Fred Hutchinson Cancer Center

Code:

NCT04370301

Conditions

Primary Myelofibrosis

Secondary Myelofibrosis

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Not accepted

Interventions

Cyclophosphamide

JAK Inhibitor

Fludarabine

Recombinant Granulocyte Colony-Stimulating Factor

Melphalan

Study Details

Brief 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. 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.

Conditions

Primary Myelofibrosis

Secondary Myelofibrosis

Study ID

NCT04370301

Start date

Feb 9, 2021

Status verified date

Jul, 2026

Completion date

Aug 31, 2029

Anticipated

Primary completion date

Apr 30, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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
  • 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

Exclusion Criteria:

  • 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
  • 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

Study Design

Enrollment

20 participants

Anticipated

Allocation

Non randomized

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 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.

experimental: 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.

Interventions

Cyclophosphamide

Given IV

JAK Inhibitor

Given PO

Fludarabine

Given IV

Recombinant Granulocyte Colony-Stimulating Factor

Given SC

Melphalan

Given IV

Mycophenolate Mofetil

Given PO

Peripheral Blood Stem Cell Transplantation

Given IV

Tacrolimus

Given IV and PO

Total-Body Irradiation

Undergo TBI

Computed Tomography

Undergo CT

Magnetic Resonance Imaging

Undergo MRI

Bone Marrow Biopsy

Undergo bone marrow biopsy and aspiration

Bone Marrow Aspiration

Undergo bone marrow biopsy and aspiration

Biospecimen Collection

Undergo blood sample collection

Echocardiography Test

Undergo ECHO

Multigated Acquisition Scan

Undergo MUGA

Primary outcome measure

  • Probability of primary and secondary graft failure [ Time Frame: Up to 5 years ]

Central Contacts and Locations

Central contacts

Rachel B. Salit

206-667-1317rsalit@fredhutch.org

Locations

Fred Hutch/University of Washington Cancer Consortium

Recruiting

Seattle, Washington, United States, 98109

Contacts

Rachel B. Salit

206-667-1317rsalit@fredhutch.org

Principal Investigator:

Rachel B. Salit

More Information

Sponsor

Fred Hutchinson Cancer Center

Last update posted

Jul 20, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Fred Hutchinson Cancer Center on 2026-07-20.