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

Ruxolitinib Based GVHD Prophylaxis Regimen for Older Adults Receiving Non-ATG Containing Non-Myeloablative Hematopoietic Cell Transplantation for Acquired Aplastic Anemia

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Aplastic Anemia
• Intervention / Treatment: Procedure: Computed Tomography; Procedure: Biospecimen Collection; Drug: Fludarabine; Drug: Mycophenolate Mofetil; Radiation: Total-Body Irradiation; Procedure: Peripheral Blood Stem Cell Transplantation; Procedure: Echocardiography; Procedure: Multigated Acquisition Scan; Drug: Sirolimus; Drug: Cyclosporine; Drug: Ruxolitinib; Procedure: Bone Marrow Biopsy; Procedure: Bone Marrow Transplantation; Procedure: Bone Marrow Aspiration; Drug: Granulocyte Colony-Stimulating Factor

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutch/University of Washington Cancer Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Prevention (conditioning, transplant, GVHD prophylaxis); See Detailed Description.

Procedure: Computed Tomography; Undergo CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Drug: Fludarabine; Given IV; Other Names: Fluradosa; Drug: Mycophenolate Mofetil; Given PO; Other Names: CellCept; MMF; Radiation: Total-Body Irradiation; Undergo TBI; Other Names: Total Body Irradiation; TBI; SCT_TBI; Whole Body Irradiation; Whole-Body Irradiation; Whole Body; Procedure: Peripheral Blood Stem Cell Transplantation; Undergo PBSC transplantation; Other Names: PBPC transplantation; Peripheral Blood Progenitor Cell Transplantation; Peripheral Stem Cell Support; Peripheral Stem Cell Transplantation; PBSCT; Peripheral Stem Cell Transplant; PERIPHERAL BLOOD STEM CELL TRANSPLANT; Peripheral Blood; Procedure: Echocardiography; Undergo ECHO; Other Names: EC; Procedure: Multigated Acquisition Scan; Undergo MUGA; Other Names: MUGA; MUGA Scan; Radionuclide ventriculography; Drug: Sirolimus; Given PO; Other Names: Rapamycin; Rapamune; AY 22989; RAPA; SILA 9268A; WY-090217; AY-22989; AY22989; SILA-9268A; SILA9268A; WY 090217; WY090217; Drug: Cyclosporine; Given PO; Other Names: 27-400; Sandimmune; Ciclosporin; CsA; Neoral; Gengraf; Cyclosporin; Cyclosporin A; OL 27-400; SangCya; Cyclosporine Modified; CyA; Drug: Ruxolitinib; Given PO; Other Names: INCB-18424; INCB18424; Oral JAK Inhibitor INCB18424; INCB-018424; INCB 018424; Procedure: Bone Marrow Biopsy; Undergo bone marrow biopsy and aspiration; Other Names: Biopsy of Bone Marrow; Biopsy, Bone Marrow; Procedure: Bone Marrow Transplantation; Undergo bone marrow transplant; Other Names: BMT; Bone Marrow Transplant; Blood and Bone Marrow Transplant; Bone Marrow Grafting; Marrow Transplantation; Bone Marrow; Procedure: Bone Marrow Aspiration; Undergo bone marrow biopsy and aspiration; Drug: Granulocyte Colony-Stimulating Factor; Given SC; Other Names: G-CSF; Granulocyte Colony Stimulating Factor; GCSF; Colony Stimulating Factor 3; Colony-Stimulating Factor (Granulocyte); Colony-Stimulating Factor 3; CSF3; G CSF; Pluripoietin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of grades II-IV acute graft-versus-host disease (GVHD)	Will be estimated as simple proportions and informally compared to the historical controls at Fred Hutch. (i.e., estimates presented descriptively, but no formal statistical comparisons will be made).	At day 100

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of grade III-IV acute GVHD	Will be estimated as simple proportions and informally compared to the historical controls at Fred Hutch. (i.e., estimates presented descriptively, but no formal statistical comparisons will be made).	At day 100
Incidence of chronic GVHD	Will be estimated as simple proportions and informally compared to the historical controls at Fred Hutch. (i.e., estimates presented descriptively, but no formal statistical comparisons will be made).	At 1 year
Incidence of primary graft failure	Will be defined as absence of 3 consecutive days with neutrophils ≥ 500/ul combined with host CD3 peripheral blood chimerism ≥ 50% at day 42; absence of 3 consecutive days with neutrophils ≥ 500/ul under any circumstances at day 55; death after day 28 with neutrophil count <100/ul without any evidence of engraftment (< 5% donor CD3) and; primary autologous count recovery with < 5% donor CD3 peripheral blood chimerism at count recovery and without relapse.	At 2 years
Nonrelapse mortality	Kaplan-Meier curve will be generated with point estimates and 95% confidence intervals, and Log-rank test will be conducted.	At day 100
Overall survival	Kaplan-Meier curve will be generated with point estimates and 95% confidence intervals, and Log-rank test will be conducted.	At 1 year

Collaborators and Investigators

• Sponsor: Fred Hutchinson Cancer Center
• Collaborators: Incyte Corporation
• Investigators: Principal Investigator: Rachel B. Salit, MD, Fred Hutch/University of Washington Cancer Consortium

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2025
• Primary Completion (Actual): January 23, 2026
• Study Completion (Estimated): October 15, 2026

Study Registration Dates

• First Submitted: December 23, 2024
• First Submitted That Met QC Criteria: December 23, 2024
• First Posted (Actual): December 31, 2024

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Marrow Failure Disorders; Hematologic Diseases; Bone Marrow Diseases; Anemia; Hemic and Lymphatic Diseases; Anemia, Aplastic; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Investigative Techniques; Therapeutics; Fatty Acids; Lipids; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Cytological Techniques; Cytodiagnosis; Biological Factors; Carbohydrates; Acids, Acyclic; Carboxylic Acids; Polycyclic Compounds; Transplantation; Diagnostic Techniques, Surgical; Macrolides; Lactones; Intercellular Signaling Peptides and Proteins; Glycoproteins; Glycoconjugates; Radiotherapy; Macrocyclic Compounds; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Peptides, Cyclic; Colony-Stimulating Factors; Hematopoietic Cell Growth Factors; Cytokines; Caproates; Stem Cell Transplantation; Tissue Transplantation; Hematopoietic Stem Cell Transplantation; Sirolimus; Mycophenolic Acid; Cyclosporine; Cyclosporins; Biopsy; Specimen Handling; fludarabine; ruxolitinib; Granulocyte Colony-Stimulating Factor; Whole-Body Irradiation; Bone Marrow Transplantation; Blood Specimen Collection; Peripheral Blood Stem Cell Transplantation
• Other Study ID Numbers: RG1124040; 20575 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium); NCI-2024-06524 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No