Status:
UNKNOWN
A Study of SKLB1028 Versus Salvage Chemotherapy in Patients With Relapsed or Refractory (R/R) AML With FLT3-Mutated
Lead Sponsor:
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Conditions:
Acute Myeloid Leukemia (AML)
Eligibility:
All Genders
18+ years
Phase:
PHASE3
Brief Summary
This is a randomized，multicenter, open-label Phase III, clinical study to confirm the efficacy and safety of SKLB1028 in patients with relapsed or refractory(R/R) FLT3-Mutated Acute Myeloid Leukemia（A...
Detailed Description
Eligible subjects will be randomized in a 2:1 ratio to receive SKLB1028 or salvage chemotherapy. Subjects will enter the screening period up to 14 days before the start of treatment. Prior to randomiz...
Eligibility Criteria
Inclusion
- Patients volunteered to participate in this study and signed the informed consent form.
- Age≥18 years old, no gender limitation.
- Patient has a diagnosis of primary AML or AML secondary to myelodysplastic syndrome (MDS) as determined by pathological and morphological results, according to World Health Organization (WHO) 2016 classification.
- Patient is refractory to or relapsed after first-line AML therapy (with or without HSCT).
- Refractory to first-line AML treatment is defined as: the patient did not achieve complete remission/complete remission with incomplete hematologic recovery/complete remission with incomplete platelet recovery (CR/CRi/CRp) under initial therapy. A patient eligible for standard therapy must receive at least 1 cycle of an anthracycline containing induction therapy in the standard dose for the selected induction regimen. A patient not eligible for standard therapy must have received at least 1 complete block of induction therapy seen as the optimum choice of therapy to induce remission for this patient as per investigator's assessment.
- Early relapse after first-line AML therapy is defined as: the patients achieved CR/CRi/CRp after first-line treatment, and relapsed within 6 months with hematological relapse.
- Advanced relapse after first-line AML therapy is defined as: the patients achieved CR/CRi/CRp after first-line treatment and relapsed after 6 months with hematological relapse;
- Patient is positive for FLT3 mutation in bone marrow or whole blood.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
- Patient is eligible for pre-selected salvage chemotherapy according to investigator assessment.
- Patient must meet the following criteria as indicated on the clinical laboratory tests:
- Serum aspartate aminotransferase and alanine aminotransferase ≤ 3.0 x upper limit of normal (ULN);
- Serum total bilirubin ≤ 1.5 x ULN;
- Serum creatinine ≤ 3.0 x ULN or an estimated glomerular filtration rate of \> 30 mL/min.
- Patient is suitable for oral administration of the study drug.
- Female or male patient of childbearing age agree to take effective non-drug contraception from the date of signing an informed consent to 180 days after the last dose and will not donate sperm or eggs.
Exclusion
- Patient was diagnosed as acute promyelocytic leukemia (APL), or BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).
- Patient has AML secondary to prior chemotherapy for other neoplasms (except for MDS).
- AML with central nervous system (CNS) involvement (defined as highly suspected CNS involvement with clinical symptoms supported by imaging evidence).
- Refractory hypokalemia or hypomagnesemia that is difficult to be corrected by symptomatic treatment and has recurred in the past.
- Patient is currently suffering from clinically significant graft-versus-host disease (GVHD) or receiving systemic cortisol hormone therapy for GVHD.
- Patient has been previously diagnosed with another malignancy (except in the following cases: disease-free for at least 5 years; Patients with treated nonmelanoma skin cancer, breast in situ carcinoma or cervical intraepithelial neoplasia \[regardless of disease status\]; Localized prostate cancer with no recurrence or progression that is expected to be cured after treatment, such as radiotherapy or surgery)
- Patient has clinically significant abnormality of coagulation profile, such as disseminated intravascular coagulation (DIC), hemophilia A, hemophilia B, and von Willebrand disease.
- Patient has had major surgery within 4 weeks prior to the study (the definition of major surgery was based on the level 3 and level 4 surgeries stipulated in the Management Measures for Clinical Application of Medical Technology), or has not fully recovered from any previous invasive operation.
- Patient has radiation therapy within 4 weeks before the first study dose.
- Patient has congestive heart failure New York Heart Association (NYHA) class 3 or 4 or patient with a history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram performed within 1 month before study entry results in a left ventricular ejection fraction that is ≥ 45%.
- Patient has bradycardia and heart rate is less than 50 beats/min, except for pacemaker user.
- Patients with mean value of triplicate Fridericia-corrected QT interval (QTcF) in the screening period, male \> 450 ms, female \> 470 ms.
- Patients with diagnosed or suspected long QT syndrome at screening (including a family history of long QT syndrome).
- Patients with second degree (Mobitz II) or third degree atrioventricular block disease (except for patients who use the pacemaker).
- Patients with uncontrolled angina or myocardial infarction in 6 months before screening.
- Patient has a complete left bundle branch block during screening.
- Patients with new clinically significant arrhythmias (except for sinus tachycardia caused by anemia, infection and AML) or patients with previous arrhythmias that require long-term use of drugs with QT-prolonging effects.
- Patient has an active uncontrolled infection.
- Patients are hepatitis B surface antigen-positive or have a history of hepatitis B, with HBV-DNA ≥2000 IU/mL in the past 3 months; Patients are hep
- Patients with positive anti-human immunodeficiency virus antibodies or anti-Treponema pallidum specific antibodies.
- Patient has cytotoxic chemotherapy drugs \<2 weeks, or non-cytotoxic drugs \<5 half-lives prior to the first study dose (except hydroxyurea and other treatments used to control hyperleucocytosis).
- Patients have taken CYP 2C8 and CYP 3A4 strong inducers or inhibitors within 2 weeks prior to the first study dose.
- Patients have previously received other FLT3 inhibitors (Gilteritinib, Quizatinib, Crenolanib, etc.), except for sorafenib.
- Pregnant (blood pregnancy test positive in screening period) and lactating Female.
- Patients are not suitable for the study in the investigator's opinion.
Key Trial Info
Start Date :
March 24 2021
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 1 2025
Estimated Enrollment :
315 Patients enrolled
Trial Details
Trial ID
NCT04716114
Start Date
March 24 2021
End Date
December 1 2025
Last Update
November 2 2021
Active Locations (1)
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1
West China hospital of Sichuan University
Chengdu, Sichuan, China