RECRUITING

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2025-05-16

Study Completion:2027-06-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06752694

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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	* 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

Inclusion Criteria

Exclusion 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

* 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

Contacts and Locations

Study Contact

Rachel B. Salit, MD

CONTACT

206-667-1317

rsalit@fredhutch.org

Principal Investigator

Rachel B. Salit, MD

PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Study Locations (Sites)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109

United States

Collaborators and Investigators

Sponsor: Fred Hutchinson Cancer Center

Rachel B. Salit, MD, PRINCIPAL_INVESTIGATOR, Fred Hutch/University of Washington Cancer Consortium

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-05-16

Study Completion Date2027-06-01

Study Record Updates

Study Start Date2025-05-16

Study Completion Date2027-06-01

Terms related to this study

Additional Relevant MeSH Terms

Aplastic Anemia