Exploring the Safety and Effectiveness of Combined Azacitidine and Ruxolitinib Therapy for Acute Erythroid Leukemia

JRCT ID: jRCTs051240090

Registered date:17/07/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: AML with erythroid predominance or genomic abnormalities associated with activatd JAK-STAT signaling
• Date of first enrollment: 05/08/2024
• Target sample size: 15
• Study type: Interventional

Intervention(s)

1 cycle is 4 weeks.
azacitidine; administer 50-75mg/m^2 subcutaneous/intravenous drip injection daily day1-5/ 4week
ruxolitinib; take 5-25 g orally twice daily every 12h for 4 weeks.

Outcome(s)

• Primary Outcome: To determine the maximum tolerated dose
• Secondary Outcome: To evaluate of efficacy and response rate

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 80age old
• Gender: Both

Include criteria

Patients fulfilling all of the following 1. - 4.
1.ECOG Performance Status (PS) is 0, 1 or 2.
2.Confirmed acute myeloid leukemia by bone marrow/peripheral blood analysis.
3.Meets either a) or b) below.
a) Patients in which 50% or more erythroblasts with dysplasia of all nucleated BM cells , or patients in which 20% or more erythroblasts are observed in the peripheral blood.
b) Patients with mutations involved in JAK-STAT signaling, including JAK2, EPOR, MPL, JAK3, and JAK1 amplification or mutation.
4.Patients with AML whose disease has relapsed, is refractory or who are intolerant to the 1st line treatment.

Exclude criteria

1. ECOG Performance Status (PS) of 3 or 4.
2. Known allergies, hypersensitivity, or intolerance to azacitidine/ruxolitinib
3. Prior treatment with any JAK1 or JAK2 inhibitor for hematological disease.
4. Presented with active uncontrolled infection requiring treatment, including high levels of HBV viral load (at levels requiring treatment).
5. Patients who had severely impaired renal function defined by: Creatinine clearance less than 30 mL/min (Cockcroft-Gault Formula).
6. History or current diagnosis of uncontrolled or significant cardiac disease, including any of the following.
a. Myocardial infarction within last 6 months
b. Uncontrolled congestive heart failure
c. Unstable angina within last 6 months
d. Clinically significant (symptomatic) cardiac arrhythmias (e.g. bradyarrhythmia, sustained ventricular tachycardia, and clinically significant second- or third-degree AV block without a pacemaker).
7. Cholestatic disorders, or unresolved sinusoidal obstructive syndrome/veno-occlusive disease of the liver (defined as persistent bilirubin abnormalities not attributable to aGvHD and ongoing organ dysfunction).
8. ALT >=200 IU/L or both total bilirubin >=3.0mg/dL and direct bilirubin >=2.0mg/dL, unrelated to AML.
9. Significant respiratory disease including patients who were on mechanical ventilation or who have resting O2 saturation <90% by pulse-oximetry in ambient air, unrelated to AML.
10. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of ruxolitinib.
11. Patients with a history or current diagnosis of progressive multifocal leuko-encephalopathy.
12. Pregnant or nursing (lactating) women.
13. Fertile women who refuse or cannot use effective contraception; Women pregnant or nursing; Women with positive test pregnancy (test before treatment initiation)

Related Information

• Primary Sponsor: Kanda Junya
• Secondary Sponsor: Ogawa Seishi,Nagai Sumimasa
• Source(s) of Monetary Support: Novartis Japan