Ruxolitinib in Treating Patients With Hypereosinophilic Syndrome or Primary Eosinophilic Disorders

NCT03801434 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: IRB-47457NCI-2018-03723HEMMPD0035
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 4

Brief Summary

This phase II trial studies how well ruxolitinib works in treating patients with hypereosinophilic syndrome or primary eosinophilic disorders.

Conditions

BCR-JAK2 Fusion Protein Expression; Blasts 20 Percent or Less of Peripheral Blood White Cells; Blasts More Than 5 Percent of Bone Marrow Nucleated Cells; Blasts More Than 5 Percent of Peripheral Blood White Cells; Blasts Under 20 Percent of Bone Marrow Nucleated Cells; Chronic Eosinophilic Leukemia, Not Otherwise Specified; Eosinophilia; Hepatomegaly; Hypereosinophilic Syndrome; JAK2 Gene Mutation; Splenomegaly; TEL-JAK2 Fusion Protein Expression

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  ORR is the sum of complete response (CR) plus complete response with incomplete platelet recovery (CRp) plus partial response (PR). Complete response, with platelet incomplete platelet recovery (CRp) is defined as a response that meets CR criteria but platelet count remains below 100 x 10\^9/L. This outcome will be reported as a number. * Complete response (CR) = normalization of white blood cell (WBC) count; absolute eosinophil count in blood; and % eosinophils in blood, without increased blasts or eosinophils in bone marrow, and with a non-palpable spleen and/ or normal spleen size by imaging. * Partial response (PR) is defined as ≥ 50% reduction (if above normal range) in all the following: total WBC count; absolute eosinophil count in blood; % eosinophils in blood; % eosinophils and myeloblasts in bone marrow; in addition to spleen size reduction of ≥ 50% by palpation and/ or ≥35% by imaging (if increased at baseline).

  3 years

Secondary Outcomes (6)

• Adverse events

  3 years

• Proportion of subjects who become corticosteroid-independent

  3 years

• Proportion of patients who reduce corticosteroid dose by >= 50% (including patients who become corticosteroid-independent)

  3 years

• Duration of response (DoR)

  3 years

• Time to response (TTR)

  3 years

Study Arms (1)

Treatment (ruxolitinib)

EXPERIMENTAL

Patients receive ruxolitinib PO BID on days 1-28. Treatment repeats for up to 6 cycles (28 days each) in the absence of disease progression or unacceptable toxicity.

Drug: Ruxolitinib

Interventions

Ruxolitinib DRUG

Given PO

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

Treatment (ruxolitinib)

Eligibility Criteria

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

You may qualify if:

• Subject with idiopathic hypereosinophilic syndrome must meet the following:
• Has as at least 2 readings with an absolute eosinophil count \>= 1,500/mm\^3 in the preceding 3 months prior to starting ruxolitinib (one reading must be during the screening period).
• Dependent, intolerant or refractory to corticosteroids OR has relapsed/refractory disease to other therapy besides corticosteroids.
• Symptomatic from his/her disease OR has one or more signs of organ damage (assessed by the investigator as possibly-related to eosinophilia or biopsy-proven). This can include skin, lung, cardiac, central nervous system, liver, or gastrointestinal (GI) involvement, or evidence of symptomatic hepatic or splenic enlargement.
• Subject with lymphocyte-variant hypereosinophilia must meet the following
• Has at least 2 readings with an absolute eosinophil count \>= 1,500/mm\^3 in the preceding 3 months prior to starting ruxolitinib (one reading must be during the screening period).
• Dependent, intolerant or refractory to corticosteroids\* OR has relapsed/refractory disease to other therapy besides corticosteroids.
• Symptomatic from his/her disease OR has one or more signs of organ damage (assessed by the investigator as possibly-related to eosinophilia or biopsy-proven). This can include skin, lung, cardiac, central nervous system, liver, or GI involvement, or evidence of symptomatic hepatic or splenic enlargement
• Has abnormal T-lymphocyte immuno-phenotype by flow cytometry.
• Subject with chronic eosinophilic leukemia, not otherwise specified (CEL,NOS) must meet the following
• Has at least 2 readings with an absolute eosinophil count \>= 500/mm\^3 in the preceding 3 months prior to starting ruxolitinib (one reading must be during the screening period).
• Newly-diagnosed OR receiving corticosteroids OR has relapsed/refractory disease to any therapy besides corticosteroids.
• Has increased blasts in the blood or bone marrow (\> 5% and \< 20%), and/or a clonal cytogenetic or molecular abnormality
• Subjects with JAK2 mutations are included within this group.
• Subject with JAK2-rearranged eosinophilic neoplasm must meet the following

You may not qualify if:

• Active life-threatening complication(s) from underlying eosinophilic disease (i.e., leukostasis; acute thromboembolic disease including central nervous system (CNS) involvement; severe pulmonary or cardiac dysfunction). Stabilization of acute, life-threatening eosinophil-related co-morbidities will allow enrollment of the patient.
• World Health Organization (WHO)-defined myeloid neoplasm associated with eosinophilia other than CEL NOS and JAK2 rearranged neoplasms (e.g., myelodysplastic syndrome (MDS); myeloproliferative neoplasms (MPN); MDS/MPN overlap disorders; and systemic mastocytosis (SM).
• Reactive hypereosinophilia due to connective tissue disease, sarcoidosis or eosinophilic granulomatosis with polyangiitis.
• Organ-restricted ?tissue? eosinophilia with the absence of peripheral eosinophilia in the blood.
• Invasive malignancy over the previous 2 years except treated early stage carcinomas of the skin, completely resected intraepithelial carcinoma of the cervix, and completely resected papillary thyroid and follicular thyroid cancers.
• Myeloid or lymphoid neoplasm with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1.
• Anticipated to receive a hematopoietic stem cell transplant within the first 6 months of treatment on trial.
• Major surgery within 4 weeks prior to entering the study.
• Life expectancy of \< 6 months.
• Known diagnosis of human immunodeficiency virus (HIV).
• Known diagnosis of chronic active hepatitis B or C (viral testing is not required). Subjects with a known history of hepatitis B and/or C are allowed on trial if at the time of enrollment, the virus is not active and undetected (testing required if there is a known history), and such patients are not actively receiving antiviral treatment specific for hepatitis B and/or C.
• Clinically serious infections requiring ongoing antibiotic therapy.
• Parasitic infection diagnosed within 24 weeks prior to enrollment.
• Platelet count =\< 25 x 10\^9/L at baseline.
• Alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) \> 4 x upper limit of normal (ULN) or direct bilirubin \> 4 x ULN (if considered to be unrelated to the underlying eosinophilic disorder).

Sponsors & Collaborators

• Incyte Corporation: collaborator
• William Shomali: lead

Study Sites (4)

Stanford Cancer Institute Palo Alto

Palo Alto, California, 94304, United States

RECRUITING

OHSU Knight Cancer Institute

Portland, Oregon, 97201, United States

TERMINATED

University of Utah

Salt Lake City, Utah, 84112, United States

TERMINATED

Fred Hutchinson cancer research center

Seattle, Washington, 98109, United States

TERMINATED

MeSH Terms

Conditions

Hypereosinophilic Syndrome; Eosinophilia; Hepatomegaly; Splenomegaly

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Liver Diseases; Digestive System Diseases; Hypertrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Officials

• William E Shomali, MD

  Stanford Cancer Institute Palo Alto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tiffany Nguyen

CONTACT

650-725-9167; tnguye10@stanford.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Assistant Professor

Study Record Dates

• First Submitted: January 9, 2019
• First Posted: January 11, 2019
• Study Start: November 15, 2019
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): December 30, 2028
• Last Updated: December 23, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)