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

NCT06752694 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: RG1124040NCI-2024-0652420575
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Aplastic Anemia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Incidence of grade III-IV acute GVHD

  At day 100

• Incidence of chronic GVHD

  At 1 year

• Incidence of primary graft failure

  At 2 years

• Nonrelapse mortality

  At day 100

• Overall survival

  At 1 year

Study Arms (1)

Prevention (conditioning, transplant, GVHD prophylaxis)

EXPERIMENTAL

See Detailed Description.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Bone Marrow Transplantation; Procedure: Computed Tomography; Drug: Cyclosporine; Drug: Fludarabine; Drug: Granulocyte Colony-Stimulating Factor; Drug: Mycophenolate Mofetil; Procedure: Peripheral Blood Stem Cell Transplantation; Drug: Ruxolitinib; Drug: Sirolimus; Radiation: Total-Body Irradiation; Procedure: Multigated Acquisition Scan; Procedure: Echocardiography

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Prevention (conditioning, transplant, GVHD prophylaxis)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow biopsy and aspiration

Prevention (conditioning, transplant, GVHD prophylaxis)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy and aspiration

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Prevention (conditioning, transplant, GVHD prophylaxis)

Bone Marrow Transplantation PROCEDURE

Undergo bone marrow transplant

Also known as: Blood and Bone Marrow Transplant, BMT, Bone Marrow, Bone Marrow Grafting, Bone Marrow Transplant, Marrow Transplantation

Prevention (conditioning, transplant, GVHD prophylaxis)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Prevention (conditioning, transplant, GVHD prophylaxis)

Cyclosporine DRUG

Given PO

Also known as: 27-400, Ciclosporin, CsA, CyA, Cyclosporin, Cyclosporin A, Cyclosporine Modified, Gengraf, Neoral, OL 27-400, Sandimmune, SangCya

Prevention (conditioning, transplant, GVHD prophylaxis)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Prevention (conditioning, transplant, GVHD prophylaxis)

Granulocyte Colony-Stimulating Factor DRUG

Given SC

Also known as: Colony Stimulating Factor 3, Colony-Stimulating Factor (Granulocyte), Colony-Stimulating Factor 3, CSF3, G CSF, G-CSF, GCSF, Granulocyte Colony Stimulating Factor, Pluripoietin

Prevention (conditioning, transplant, GVHD prophylaxis)

Mycophenolate Mofetil DRUG

Given PO

Also known as: CellCept, MMF

Prevention (conditioning, transplant, GVHD prophylaxis)

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo PBSC transplantation

Also known as: 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

Prevention (conditioning, transplant, GVHD prophylaxis)

Ruxolitinib DRUG

Given PO

Also known as: INCB 018424, INCB-018424, INCB-18424, INCB18424, Oral JAK Inhibitor INCB18424

Prevention (conditioning, transplant, GVHD prophylaxis)

Sirolimus DRUG

Given PO

Also known as: AY 22989, AY-22989, AY22989, RAPA, Rapamune, Rapamycin, SILA 9268A, SILA-9268A, SILA9268A, WY 090217, WY-090217, WY090217

Prevention (conditioning, transplant, GVHD prophylaxis)

Total-Body Irradiation RADIATION

Undergo TBI

Also known as: SCT_TBI, TBI, Total Body Irradiation, Whole Body, Whole Body Irradiation, Whole-Body Irradiation

Prevention (conditioning, transplant, GVHD prophylaxis)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: MUGA, MUGA Scan, Radionuclide ventriculography

Prevention (conditioning, transplant, GVHD prophylaxis)

Echocardiography PROCEDURE

Undergo ECHO

Also known as: EC

Prevention (conditioning, transplant, GVHD prophylaxis)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• Incyte Corporation: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Conditions

Anemia, Aplastic

Interventions

Specimen Handling; Biopsy; Bone Marrow Transplantation; Blood Specimen Collection; Cyclosporine; Cyclosporins; fludarabine; Granulocyte Colony-Stimulating Factor; Mycophenolic Acid; Peripheral Blood Stem Cell Transplantation; ruxolitinib; Sirolimus; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Tissue Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Punctures; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Proteins; Biological Factors; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Macrolides; Lactones; Radiotherapy

Study Officials

• Rachel B. Salit, MD

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rachel B. Salit, MD

CONTACT

206-667-1317; rsalit@fredhutch.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2024
• First Posted: December 31, 2024
• Study Start: September 25, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 12, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)