Ruxolitinib Based GVHD Prophylaxis Regimen Before, During, and After Hematopoietic Cell Transplantation in Older Adult Patients With Acquired Aplastic Anemia

NCT ID: NCT06752694

Last Updated: 2025-09-30

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

2025-09-25

Study Completion Date

2027-06-01

Brief Summary

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This phase II trial tests how well a ruxolitinib-based graft versus host disease (GVHD) prevention (prophylaxis) regimen works before, during, and after bone marrow/stem cell transplantation (hematopoietic cell transplantation \[HCT\]) in patients with acquired aplastic anemia. Acquired aplastic anemia (AA) is a condition in which the bone marrow is unable to produce blood cells. Affected patients typically present with infections due to abnormally low number of neutrophils, bleeding due to low platelet count, and/or fatigue due to a lower-than-normal number of red blood cells (anemia). Its incidence varies with age, occurring most frequently in patients aged 2-5 years, 20-25 years, and 55 years and older. Treatment of AA includes either immunosuppressive therapy (IST) or bone marrow/stem cell transplantation (HCT) with first-line therapy in younger adults often being HCT, while adults over 40 still frequently trial IST first due to the morbidity and mortality concerns with HCT. GVHD is a common complication after donor stem cell transplantation, resulting from donor immune cells recognizing recipients' cells and attacking them. Ruxolitinib, a drug in a class of oral medications called JAK inhibitors has been approved for the treatment of acute and chronic GVHD. It has also been shown to decrease GVHD when used in the prevention setting in patients with myelofibrosis. The current study aims to assess whether adding ruxolitinib to a standard GVHD prevention regimen may reduce the risk of Grade II-IV acute and chronic GVHD after bone marrow/stem cell transplantation in older patients with acquired aplastic anemia.

Detailed Description

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OUTLINE:

CONDITIONING REGIMEN: Patients receive fludarabine intravenously (IV) over 30 minutes once daily (QD) on days -4, -3, and -2 and undergo total body irradiation (TBI) in one or two fractions on day -1.

TRANSPLANT: Patients undergo peripheral blood stem cell (PBSC) or bone marrow transplant on day 0.

GVHD PROPHYLAXIS: Cyclosporine, Sirolimus, mycophenolate mofetil (MMF), Ruxolitinib

HUMAN LEUKOCYTE ANTIGEN (HLA)-MATCHED: Patients receive cyclosporine orally (PO) every 12 hours (Q12H) on days -3 to 96 with taper beginning on day 97 until day 180 (until day 150 for patients with unrelated donors), ruxolitinib PO twice daily (BID) or QD on day -5 to 365 and mycophenolate mofetil (MMF) PO 4-6 hours after transplant and then every 8 hours (Q8H) until day 29, then reduced to Q12H on days 30-40. Patients with unrelated donors also receive sirolimus PO QD on days -3 to 150 with taper beginning on day 151 until day 180. Patients also begin granulocyte colony-stimulating factor (G-CSF) subcutaneously (SC) on day 1 to continue until absolute neutrophil count (ANC) \> 1000/mm\^3 x 3 days. Patients also undergo multi-gated acquisition scan (MUGA)/echocardiogram (ECHO) and computed tomography (CT) during screening, as well as collection of blood samples and bone marrow aspiration and biopsy throughout the study.

HLA-MISMATCHED: Patients receive cyclosporine PO Q12 on days -3 to 150 with taper beginning on day 151 until day 180, sirolimus PO QD on days -3 to 180 with taper beginning on day 181 until day 365, ruxolitinib PO BID or QD on day -5 to 365, and MMF PO 4-6 hours after transplant and then Q8 until day 29, then reduced to Q12H on days 30-40. Patients also begin G-CSF SC on day 1 to continue until ANC \> 1000/mm\^3 x 3 days.

Patients also undergo MUGA/ECHO and CT during screening, as well as collection of blood samples and bone marrow aspiration and biopsy throughout the study.

Conditions

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Aplastic Anemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Prevention (conditioning, transplant, GVHD prophylaxis)

See Detailed Description.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Bone Marrow Aspiration

Intervention Type PROCEDURE

Undergo bone marrow biopsy and aspiration

Bone Marrow Biopsy

Intervention Type PROCEDURE

Undergo bone marrow biopsy and aspiration

Bone Marrow Transplantation

Intervention Type PROCEDURE

Undergo bone marrow transplant

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Cyclosporine

Intervention Type DRUG

Given PO

Fludarabine

Intervention Type DRUG

Given IV

Granulocyte Colony-Stimulating Factor

Intervention Type DRUG

Given SC

Mycophenolate Mofetil

Intervention Type DRUG

Given PO

Peripheral Blood Stem Cell Transplantation

Intervention Type PROCEDURE

Undergo PBSC transplantation

Ruxolitinib

Intervention Type DRUG

Given PO

Sirolimus

Intervention Type DRUG

Given PO

Total-Body Irradiation

Intervention Type RADIATION

Undergo TBI

Multigated Acquisition Scan

Intervention Type PROCEDURE

Undergo MUGA

Echocardiography

Intervention Type PROCEDURE

Undergo ECHO

Interventions

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Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Bone Marrow Aspiration

Undergo bone marrow biopsy and aspiration

Intervention Type PROCEDURE

Bone Marrow Biopsy

Undergo bone marrow biopsy and aspiration

Intervention Type PROCEDURE

Bone Marrow Transplantation

Undergo bone marrow transplant

Intervention Type PROCEDURE

Computed Tomography

Undergo CT

Intervention Type PROCEDURE

Cyclosporine

Given PO

Intervention Type DRUG

Fludarabine

Given IV

Intervention Type DRUG

Granulocyte Colony-Stimulating Factor

Given SC

Intervention Type DRUG

Mycophenolate Mofetil

Given PO

Intervention Type DRUG

Peripheral Blood Stem Cell Transplantation

Undergo PBSC transplantation

Intervention Type PROCEDURE

Ruxolitinib

Given PO

Intervention Type DRUG

Sirolimus

Given PO

Intervention Type DRUG

Total-Body Irradiation

Undergo TBI

Intervention Type RADIATION

Multigated Acquisition Scan

Undergo MUGA

Intervention Type PROCEDURE

Echocardiography

Undergo ECHO

Intervention Type PROCEDURE

Other Intervention Names

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Biological Sample Collection Biospecimen Collected Specimen Collection Biopsy of Bone Marrow Biopsy, Bone Marrow Blood and Bone Marrow Transplant BMT Bone Marrow Bone Marrow Grafting Bone Marrow Transplant Marrow Transplantation CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography Computerized Tomography (CT) scan CT CT Scan tomography 27-400 Ciclosporin CsA CyA Cyclosporin Cyclosporin A Cyclosporine Modified Gengraf Neoral OL 27-400 Sandimmune SangCya Fluradosa Colony Stimulating Factor 3 Colony-Stimulating Factor (Granulocyte) Colony-Stimulating Factor 3 CSF3 G CSF G-CSF GCSF Granulocyte Colony Stimulating Factor Pluripoietin CellCept MMF PBPC transplantation PBSCT Peripheral Blood Peripheral Blood Progenitor Cell Transplantation PERIPHERAL BLOOD STEM CELL TRANSPLANT Peripheral Stem Cell Support Peripheral Stem Cell Transplant Peripheral Stem Cell Transplantation INCB 018424 INCB-018424 INCB-18424 INCB18424 Oral JAK Inhibitor INCB18424 AY 22989 AY-22989 AY22989 RAPA Rapamune Rapamycin SILA 9268A SILA-9268A SILA9268A WY 090217 WY-090217 WY090217 SCT_TBI TBI Total Body Irradiation Whole Body Whole Body Irradiation Whole-Body Irradiation MUGA MUGA Scan Radionuclide ventriculography EC

Eligibility Criteria

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Inclusion Criteria

* Age \> 40 years or ages 18 - 40 years with Hematopoietic Cell Transplantation - Specific Comorbidity Index (HCT-CI) score \> 3 necessitating a low intensity transplant or determined inability to tolerate antithymocyte globulin (ATG)
* Diagnosis of severe acquired aplastic anemia defined as a bone marrow hypoplasia (\< 25% or 25-50% with \< 30% residual hematopoietic cells) shown by a biopsy and at least two of the three following criteria: absolute neutrophil count (ANC) \< 0.5×10\^9/L, platelets \< 20×10\^9/L, or absolute reticulocytes \< 40×10\^9/L or
* Non-severe acquired aplastic anemia defined as a hypocellular marrow and transfusion dependent (red cells and/or platelets)
* Does not meet World Health Organization (WHO) criteria for myelodysplastic syndrome (MDS)
* 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
* Karnofsky ≥ 70
* Calculated creatinine clearance using the Cockcroft-Gault formula or 24 hr urine creatinine clearance must be \> 60 ml/min
* Total serum bilirubin must be \< 2 mg/dL unless the elevation is thought to be due to Gilbert's disease or hemolysis
* Transaminases must be \< 3x 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
* Diffusing capacity for carbon monoxide (DLCO) corrected \> 60% normal
* May not be on supplemental oxygen
* Left ventricular ejection fraction \> 40% OR shortening fraction \> 26%
* Patients may have received prior treatment for their AA but they are NOT required to have received immune suppression prior to consideration for transplant

Exclusion Criteria

* Contraindication to receiving ruxolitinib including: patients who have known hypersensitivity to JAK inhibitors and excipients
* Patients with history of myocardial infarction (MI), cerebrovascular accident (CVA) or unprovoked pulmonary embolism (PE)/deep vein thrombosis (DVT) in past 6 months
* History of prior allogeneic transplant
* Active or recent infection without infectious disease (ID) consult and approval
* History of untreated tuberculosis (TB)
* History of HIV infection
* Pregnant or breastfeeding
* History of prior malignancy with \> 20% risk of recurrence in the next 5 years
* Patients without an HLA-identical sibling donor, 10 of 10 HLA-matched or 9 of 10 mismatched unrelated donor that meet transplant criteria
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Incyte Corporation

INDUSTRY

Sponsor Role collaborator

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, MD

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, MD

Role: CONTACT

206-667-1317

Facility Contacts

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Rachel B. Salit, MD

Role: primary

206-667-1317

Other Identifiers

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NCI-2024-06524

Identifier Type: REGISTRY

Identifier Source: secondary_id

20575

Identifier Type: OTHER

Identifier Source: secondary_id

RG1124040

Identifier Type: -

Identifier Source: org_study_id

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