Ruxolitinib in Treating Patients with Hypereosinophilic Syndrome or Primary Eosinophilic Disorders

NCT ID: NCT03801434

Last Updated: 2024-12-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-15
• Study Completion Date: 2025-11-30

Brief Summary

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

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the overall hematologic response rate to ruxolitinib in patients with hypereosinophilic syndrome and primary eosinophilic disorders.

SECONDARY OBJECTIVES:

I. To determine safety profile of ruxolitinib in patients with hypereosinophilic syndrome and primary eosinophilic disorders.

II. To determine the proportion of patients on corticosteroids who are able to become corticosteroid-independent and/or reduce the dose by >= 50%.

III. To evaluate the duration of response (DoR). IV. To evaluate the time-to-response (TTR). V. To evaluate progression-free survival (PFS) and overall survival.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (ruxolitinib)

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.

Group Type: EXPERIMENTAL

Ruxolitinib

Intervention Type: DRUG

Given PO

Interventions

Ruxolitinib

Given PO

Intervention Type: DRUG

Other Intervention Names

INCB-18424; INCB18424; Oral JAK Inhibitor INCB18424

Eligibility Criteria

Inclusion Criteria

• 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

• 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.

• This group includes subjects with PCM1-JAK2, BCR-JAK2, ETV6-JAK2 or other JAK2 rearrangements.
• If receiving corticosteroids, must be a stable dose for >= 28 days prior to Day 1 (unstable dosing not eligible).
• Eastern Cooperative Oncology Group (ECOG) performance status =< 3.
• Willing and able to review and execute informed consent (legally-authorized consent acceptable).

Exclusion Criteria

• 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).
• End-stage renal function (creatinine clearance [CrCl] < 15 mL/min or glomerular filtration rate [GFR] < 15 mL/min) regardless of whether hemodialysis is required.
• Use of investigational or commercial therapies with the intent to treat the underlying eosinophilic disorder within 28 days of study start, including interferon; imatinib; alemtuzumab; cyclosporine; methotrexate; mepolizumab; benralizumab; or other antibody therapies.
• Use of hydroxyurea within 7 days of study start.
• Prior therapy with ruxolitinib or other JAK inhibitors.
• Previous allergic reactions to JAK inhibitors or excipients.
• Unwilling to commit to abstinence from heterosexual contact or agree to use and comply with highly effective contraception, 28 days prior to starting study drug, during the treatment period and for 12 weeks after discontinuation of study treatment.
• Females of childbearing potential who have a positive pregnancy test (urine or serum) during screening period.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Incyte Corporation

INDUSTRY

Sponsor Role: collaborator

William Shomali

OTHER

Sponsor Role: lead

Responsible Party

William Shomali

Clinical Assistant Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

William E Shomali, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford Cancer Institute Palo Alto

Locations

Stanford Cancer Institute Palo Alto

Palo Alto, California, United States

Site Status: RECRUITING

OHSU Knight Cancer Institute

Portland, Oregon, United States

Site Status: TERMINATED

University of Utah

Salt Lake City, Utah, United States

Site Status: TERMINATED

Fred Hutchinson cancer research center

Seattle, Washington, United States

Site Status: TERMINATED

Countries

United States

Central Contacts

Tiffany Nguyen

Role: CONTACT

Phone: 650-725-9167

Email: tnguye10@stanford.edu

Facility Contacts

William E Shomali

Role: primary

William E Shomali

Role: backup

Other Identifiers

NCI-2018-03723

Identifier Type: REGISTRY

Identifier Source: secondary_id

HEMMPD0035

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-47457

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-47457

Identifier Type: -

Identifier Source: org_study_id