Ruxolitinib in Treating Patients With Hypereosinophilic Syndrome or Primary Eosinophilic Disorders
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|ClinicalTrials.gov Identifier: NCT03801434|
Recruitment Status : Not yet recruiting
First Posted : January 11, 2019
Last Update Posted : January 11, 2019
|Condition or disease||Intervention/treatment||Phase|
|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||Drug: Ruxolitinib||Phase 2|
I. To determine the overall hematologic response rate to ruxolitinib in patients with hypereosinophilic syndrome and primary eosinophilic disorders.
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.
I. To evaluate the ability of ruxolitinib to elicit morphologic and cytogenetic/molecular remissions in patients with baseline clonal abnormalities.
II. To assess whether hematologic responses correlate with certain types of mutations on myeloid mutation panel testing and/or by flow immunophenotyping of T-cells in patients with lymphocyte-variant hypereosinophilia.
III. To determine whether improvement in organ damage is observed in patients with baseline organ dysfunction.
IV. To determine whether improvement in symptoms is observed based on a modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF).
V. To evaluate biologic correlates of response including ribonucleic acid (RNA) sequencing (RNAseq) and JAK-STAT activation status (JAK2 and/or STAT3 phosphorylation) of eosinophils from whole blood and/or marrow.
Patients receive ruxolitinib orally (PO) twice daily (BID) on days 1-28. Treatment repeats for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 4-6 weeks and every 6 months for up to 3 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase 2 Study of Ruxolitinib in Idiopathic Hypereosinophilic Syndrome and Primary Eosinophilic Disorders|
|Estimated Study Start Date :||June 19, 2019|
|Estimated Primary Completion Date :||April 30, 2021|
|Estimated Study Completion Date :||June 19, 2024|
Experimental: Treatment (ruxolitinib)
Patients receive ruxolitinib PO BID on days 1-28. Treatment repeats for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
- Overall response rate (ORR) [ Time Frame: Up to 3 years ]
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).
- All cause mortality [ Time Frame: Up to 3 years ]Per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Descriptive analysis of the incidence, severity, seriousness, and relatedness of adverse events will be reported.This outcome will be reported as all cause mortality; all serious adverse events; and those adverse events with frequency ≥ 10%. The outcomes will be reported as numbers
- Proportion of subjects who become corticosteroid-independent [ Time Frame: Up to 3 years ]Descriptive analysis of the proportion of subjects who become corticosteroid-independent for 12 or more consecutive weeks will be reported. The outcomes will be reported as number
- Proportion of patients who reduce corticosteroid dose by >= 50% (including patients who become corticosteroid-independent) [ Time Frame: Up to 3 years ]Descriptive analysis of the proportion of subjects who reduce corticosteroid dose by >= 50% (including patients who become corticosteroid-independent) for 12 or more consecutive weeks will be reported. The outcomes will be reported as number
- Duration of response (DoR) [ Time Frame: Up to 3 years ]Median duration of response (DoR) defined as the time from first onset of confirmed response to the date of first documented and confirmed progression or death due to hypereosinophilic syndrome or a primary eosinophilic neoplasm. This outcome will be reported as the median with full range, for those subjects that achieve a clinical response. Response defined as per the Primary Outcome.
- Time to response (TTR) [ Time Frame: Up to 3 years ]Median time to response (TTR) is defined as the time from start of treatment until the date of onset of a confirmed response. This outcome will be reported as the median with full range, for those subjects that achieve a clinical response.
- Median Progression-free survival (PFS) [ Time Frame: Up to 3 years ]Median progression free survival (PFS) is defined as the time from start of treatment to the date of the first documented and confirmed progression or death or institution of new therapy. This outcome will be reported as the median with full range. Progression is defined as ≥ 25% in one of the following when compared to baseline: total WBC count; absolute eosinophil count in blood; or % eosinophils in blood; OR the presence of ≥ 20% blasts in the peripheral blood or bone marrow ("evolution to AML"), with any lab finding confirmed at 2 weeks; or ≥ 25% increase in spleen size.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03801434
|Contact: Justin Abuelfirstname.lastname@example.org|
|United States, California|
|Stanford Cancer Institute Palo Alto||Not yet recruiting|
|Palo Alto, California, United States, 94304|
|Contact: Jason Gotlib 650-498-6000 email@example.com|
|Principal Investigator: Jason Gotlib|
|Principal Investigator:||Jason Gotlib, MD, MS||Stanford Cancer Institute Palo Alto|