Back to resultsSKLB1028, Daunorubicin, and Cytarabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
Primary Purpose
Newly Diagnosed Acute Myeloid Leukemia (AML)
Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
SKLB1028 Dose Escalation
Sponsored by
About this trial
This is an interventional treatment trial for Newly Diagnosed Acute Myeloid Leukemia (AML)
Eligibility Criteria
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;
- Serum aspartate aminotransf
- Total serum bilirubin ≤ 2.5 x institutional ULN
- Serum creatinine ≤ 3 x institutional ULN or an estimated glomerular filtration rate (eGFR) of > 30 ml/min
- Subject is suitable for oral administration of study drug.
Exclusion Criteria:
- Confirmed diagnosis of acute promyelocytic leukemia (M3 /APL), or BCR-ABL positive leukemia (ie, blast crisis of chronic myelogenous leukemia);
- Diagnosis of active malignancy other than AML;
- AML secondary to radiotherapy or chemotherapy for other tumors;
- AML with central nervous system involvement;
- Refractory hypokalemia or hypomagnesemia that is not easily corrected by symptomatic treatment and that occurs repeatedly in the past;
- Current clinically significant graft-ve
- Previous history of other malignancies.
- Patients with clinically significant coagulation abnormalities, such as disseminated intravascular coagulation (DIC), hemophilia A, hemophilia B, and von Willebrand disease;
- Major surgery of major organs has been performed before entering the study (for the definition of major surgery, refer to Grade 3 and 4 surgery specified in Management Measures for Clinical Application of Medical Technology, or the patient has not yet fully recovered from
- Subject has received prior therapy for AML with the following exceptions: a. emergency leukapheresis; b. emergency treatment with hydroxyurea ;c. growth factor or cytokine support; d. steroid for anaphylaxis or transfusion reaction;
Sites / Locations
- West China Hospital of Sichuan UniversityRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
SKLB1028 Dose Escalation
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Pharmacokinetics profile of SKLB1028
Observed trough concentration (Ctrough)
CR rate after the induction therapy
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.
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).
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
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.
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).
Rate of hematopoietic stem cell transplantation
Transplantation rate is defined as the percentage of participants undergoing hematopoietic stem cell transplant (HSCT).
Full Information
NCT ID
NCT05445154
First Posted
June 4, 2021
Last Updated
June 30, 2022
Sponsor
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT05445154
Brief Title
SKLB1028, Daunorubicin, and Cytarabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
Official Title
A Single-Arm, Multicenter, Open-Label, Dose- Escalating and Expanding,Phase I/II Study of SKLB1028 Combined With "7+3" Standard Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
August 31, 2021 (Actual)
Primary Completion Date
October 31, 2024 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
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 .
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Newly Diagnosed Acute Myeloid Leukemia (AML)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
58 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
SKLB1028 Dose Escalation
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
SKLB1028 Dose Escalation
Intervention Description
Drug :SKLB1028 ;Drug: Cytarabine ;Drug: Daunorubicin
Primary Outcome Measure Information:
Title
Number of participants with dose limiting toxicities (DLTs)
Description
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.
Time Frame
up to Day42
Secondary Outcome Measure Information:
Title
Pharmacokinetics profile of SKLB1028
Description
Observed trough concentration (Ctrough)
Time Frame
Days 8, 15, 18, and 21 for remission induction and Days 8, and 21 for consolidation and Days 1 for maintenance
Title
CR rate after the induction therapy
Description
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.
Time Frame
up to 3months
Title
Duration of remission
Description
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).
Time Frame
up to 24months
Title
Overall Survival
Description
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
Time Frame
up to 60months
Title
Event-Free Survival
Description
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.
Time Frame
up to 24months
Title
Leukemia-free survival
Description
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).
Time Frame
up to 24months
Title
Rate of hematopoietic stem cell transplantation
Description
Transplantation rate is defined as the percentage of participants undergoing hematopoietic stem cell transplant (HSCT).
Time Frame
up to 12months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
59 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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;
Serum aspartate aminotransf
Total serum bilirubin ≤ 2.5 x institutional ULN
Serum creatinine ≤ 3 x institutional ULN or an estimated glomerular filtration rate (eGFR) of > 30 ml/min
Subject is suitable for oral administration of study drug.
Exclusion Criteria:
Confirmed diagnosis of acute promyelocytic leukemia (M3 /APL), or BCR-ABL positive leukemia (ie, blast crisis of chronic myelogenous leukemia);
Diagnosis of active malignancy other than AML;
AML secondary to radiotherapy or chemotherapy for other tumors;
AML with central nervous system involvement;
Refractory hypokalemia or hypomagnesemia that is not easily corrected by symptomatic treatment and that occurs repeatedly in the past;
Current clinically significant graft-ve
Previous history of other malignancies.
Patients with clinically significant coagulation abnormalities, such as disseminated intravascular coagulation (DIC), hemophilia A, hemophilia B, and von Willebrand disease;
Major surgery of major organs has been performed before entering the study (for the definition of major surgery, refer to Grade 3 and 4 surgery specified in Management Measures for Clinical Application of Medical Technology, or the patient has not yet fully recovered from
Subject has received prior therapy for AML with the following exceptions: a. emergency leukapheresis; b. emergency treatment with hydroxyurea ;c. growth factor or cytokine support; d. steroid for anaphylaxis or transfusion reaction;
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Liu Ting, Chief doctor
Phone
+8618980601240
Email
liuting@scu.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Wang Jianxiang, Chief doctor
Email
wangjx@ihcams.ac.cn
Facility Information:
Facility Name
West China Hospital of Sichuan University
City
Chengdu
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Liu Ting, Chief doctor
12. IPD Sharing Statement
Learn more about this trial
SKLB1028, Daunorubicin, and Cytarabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
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