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The purpose of this study is to describe the dose limiting toxicities (DLT) of SKLB1028 when combined with cytarabine/ daunorubicin remission induction in a 7+3 schedule. Safety and tolerability of SKLB1028 will also be evaluated. This study will also characterize the pharmacokinetics (PK) of SKLB1028 when given in combination with cytarabine/daunorubicin remission induction and high-dose cytarabine (HiDAC) consolidation therapy in newly diagnosed acute myeloid leukemia .
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SKLB1028 Dose Escalation | Experimental | Part1:Patients will receive a standard combination of chemotherapy drugs during remission induction therapy that includes cytarabine, daunorubicin, and the experimental drug SKLB1028.SKLB1028 capsules beginning at 100 mg bid. Part2: Once the appropriate therapeutic schedule has been established in Part 1, up to 20 subjects will be enrolled into an expansion cohort. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SKLB1028 Dose Escalation | Drug | Drug :SKLB1028 ;Drug: Cytarabine ;Drug: Daunorubicin |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with dose limiting toxicities (DLTs) | A DLT is defined as any Grade ≥ 3 non-hematologic or extramedullary toxicity that occur during the DLT assessment period, and that is considered to be possibly, probably, or definitely related to onsolidation therapies including the study drugs. | up to Day42 |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics profile of SKLB1028 | Observed trough concentration (Ctrough) | Days 8, 15, 18, and 21 for remission induction and Days 8, and 21 for consolidation and Days 1 for maintenance |
| CR rate after the induction therapy |
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Inclusion Criteria:
Subject has a diagnosis of previously-untreated de novo acute myeloid leukemia (AML) > 20% blasts in the bone marrow according to WHO classification (2016) documented prior to enrollment.;
Age ≥ 18 and < 60 years;
Subjects who are positive for FLT3 mutations by central laboratory;
Subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2;
Subject must meet the following criteria as indicated on the clinical laboratory tests;
Subject is suitable for oral administration of study drug.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Liu Ting, Chief doctor | Contact | +8618980601240 | liuting@scu.edu.cn | |
| Wang Jianxiang, Chief doctor | Contact | wangjx@ihcams.ac.cn |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| West China Hospital of Sichuan University | Recruiting | Chengdu | China |
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CR is defined as a morphologically leukemia-free state at the post-baseline visit, having a neutrophil count of ≥ 1,000/mm^3 and platelet count of ≥ 100,000/mm^3, bone marrow blasts < 5%. There must be no evidence of Auer rods and no evidence of extramedullary leukemia.
| up to 3months |
| Duration of remission | Duration of remission included duration of composite complete remission (CRc), duration of complete remission (CR)/ complete remission with partial hematologic recovery (CRh), duration of CRh, duration of CR and duration of response (CRc + partial remission (PR). | up to 24months |
| Overall Survival | OS was measured from the date of the first dose of treatment to the date of death from any cause or to the last date that the patient was known to be alive | up to 60months |
| Event-Free Survival | EFS was defined as the time from randomization until treatment failure (Composite complete remission (CRc) or partial remission (PR) were not reached within 4 cycles), relapse (excluding relapse after PR), or death from any cause, whichever occurs first. | up to 24months |
| Leukemia-free survival | The LFS was defined as the time from the date of first CR until the date of documented relapse (excluding relapse from PR) or death for participants who achieved CR (relapse date or death date - first CR disease assessment date + 1). | up to 24months |
| Rate of hematopoietic stem cell transplantation | Transplantation rate is defined as the percentage of participants undergoing hematopoietic stem cell transplant (HSCT). | up to 12months |