Back to resultsA Trial of AK117 (Anti-CD47 Antibody) in Patients With Acute Myeloid Leukemia
Primary Purpose
Acute Myeloid Leukemia
Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
AK117
Azacitidine
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia
Eligibility Criteria
Inclusion Criteria:
- Age ≥18 years (at the time consent is obtained).
- Be able and willing to provide written informed consent and to comply with all requirements of study participation (including all study procedures).
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 3，and 0~2 are required for subjects ≥75 years old.
- Has a life expectancy of at least 12 weeks.
- Patient with AML diagnosed according to WHO 2016 criteria.
- Has adequate organ function.
- All female and male subjects of reproductive potential must agree to use an effective method of contraception, as determined by the Investigator, during and for 120 days after the last dose of study treatment.
Exclusion Criteria:
- Patient has acute promyelocytic leukemia.
- Patient has known active central nervous system (CNS) involvement with AML.
- Favorable risk cytogenetics such as t(8;21), inv(16) or t(16;16) or t(15;17) as per the National Comprehensive Cancer Network (NCCN) Guidelines Version 2, 2021 for AML.
- Is currently participating in a study of an investigational agent or using an investigational device.
- Has undergone major surgery within 30 days of Study Day 1.
- Has a known additional malignancy that is progressing or requires systemic treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
- Previous allogeneic hematopoietic stem cell transplant (allo-HSCT) .
- Prior treatment with any anti-CD47 or anti-SIRPα (signal regulatory protein alpha) agent.
- Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of this subject to participate, in the opinion of the treating investigator.
- Has received a live virus vaccine within 30 days of the planned first dose of study therapy.
- Is pregnant, breastfeeding, or expecting to conceive or father a child within the projected duration of the study including 120 days following the last dose of study treatment.
- Patient with known allergy or hypersensitivity to AK117, azacitidine or any of their components.
Sites / Locations
- The First Affiliated Hospital，Zhejiang University School of MedicineRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
AK117+Azacitidine
Arm Description
Phase Ib: Subjects will receive different doses of A117 in combination with azacitidine 75 mg/m2 subcutaneous daily for 7 days of a 28 day cycle; Phase II: Subjects will receive AK117 at the recommended Phase 2 dose in combination with azacitidine 75 mg/m2 subcutaneous daily for 7 days of a 28-day cycle.
Outcomes
Primary Outcome Measures
Composite complete remission rate （complete remission + complete remission with incomplete count recovery）
Number of participants achieving a complete remission (CR) and complete remission with incomplete hematologic recovery (CRi) per European LeukemiaNet (ELN) 2017 criteria.
Number of participants with adverse events (AEs)
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Secondary Outcome Measures
Rate of CR Without Minimal Residual Disease (CR MRD-)
The rate of CR MRD- is the percentage of participants who achieve a CR MRD- as defined by investigators based on ELN 2017 criteria.
Duration of complete response (DoCR)
The DoCR is measured from the time the assessment criteria are first met for CR (including CR MRD- and CR MRD+/unk) until the first date of AML relapse or death.
Overall Survival
The OS is measured from the date of treatment to the date of death from any cause.
Event-Free Survival (EFS)
The EFS is defined as time from the date of treatment to the earliest date of documented relapse from complete remission (CR), treatment failure , or death from any cause.
Maximum observed concentration (Cmax) of AK117
Serum concentrations of AK117 in individual subjects at different time points after AK117 administration.
Anti-drug antibodies (ADA)
Number of subjects with detectable anti-drug antibodies (ADA).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04980885
Brief Title
A Trial of AK117 (Anti-CD47 Antibody) in Patients With Acute Myeloid Leukemia
Official Title
A Phase Ib/II Trial of AK117 (Anti-CD47 Antibody) in Patients With Acute Myeloid Leukemia
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
August 13, 2021 (Actual)
Primary Completion Date
July 2023 (Anticipated)
Study Completion Date
July 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Akeso
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a open label, phase Ib/II study. All patients are diagnosed with AML, Eastern Cooperative Oncology Group (ECOG) performance status 0-3. The purpose of this study is to evaluate the safety and efficacy of AK117 + azacitidine in subjects with AML.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
160 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
AK117+Azacitidine
Arm Type
Experimental
Arm Description
Phase Ib: Subjects will receive different doses of A117 in combination with azacitidine 75 mg/m2 subcutaneous daily for 7 days of a 28 day cycle;
Phase II: Subjects will receive AK117 at the recommended Phase 2 dose in combination with azacitidine 75 mg/m2 subcutaneous daily for 7 days of a 28-day cycle.
Intervention Type
Drug
Intervention Name(s)
AK117
Intervention Description
Subjects receive AK117 intravenously.
Intervention Type
Drug
Intervention Name(s)
Azacitidine
Intervention Description
Subjects receive Azacitidine subcutaneously.
Primary Outcome Measure Information:
Title
Composite complete remission rate （complete remission + complete remission with incomplete count recovery）
Description
Number of participants achieving a complete remission (CR) and complete remission with incomplete hematologic recovery (CRi) per European LeukemiaNet (ELN) 2017 criteria.
Time Frame
Approximately 6 months
Title
Number of participants with adverse events (AEs)
Description
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Time Frame
Up to approximately 2 years.
Secondary Outcome Measure Information:
Title
Rate of CR Without Minimal Residual Disease (CR MRD-)
Description
The rate of CR MRD- is the percentage of participants who achieve a CR MRD- as defined by investigators based on ELN 2017 criteria.
Time Frame
Approximately 6 months
Title
Duration of complete response (DoCR)
Description
The DoCR is measured from the time the assessment criteria are first met for CR (including CR MRD- and CR MRD+/unk) until the first date of AML relapse or death.
Time Frame
Approximately 6 months
Title
Overall Survival
Description
The OS is measured from the date of treatment to the date of death from any cause.
Time Frame
Up to death or end of study
Title
Event-Free Survival (EFS)
Description
The EFS is defined as time from the date of treatment to the earliest date of documented relapse from complete remission (CR), treatment failure , or death from any cause.
Time Frame
Up to end of study
Title
Maximum observed concentration (Cmax) of AK117
Description
Serum concentrations of AK117 in individual subjects at different time points after AK117 administration.
Time Frame
Up to 2 years.
Title
Anti-drug antibodies (ADA)
Description
Number of subjects with detectable anti-drug antibodies (ADA).
Time Frame
Up to 2 years.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥18 years (at the time consent is obtained).
Be able and willing to provide written informed consent and to comply with all requirements of study participation (including all study procedures).
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 3，and 0~2 are required for subjects ≥75 years old.
Has a life expectancy of at least 12 weeks.
Patient with AML diagnosed according to WHO 2016 criteria.
Has adequate organ function.
All female and male subjects of reproductive potential must agree to use an effective method of contraception, as determined by the Investigator, during and for 120 days after the last dose of study treatment.
Exclusion Criteria:
Patient has acute promyelocytic leukemia.
Patient has known active central nervous system (CNS) involvement with AML.
Favorable risk cytogenetics such as t(8;21), inv(16) or t(16;16) or t(15;17) as per the National Comprehensive Cancer Network (NCCN) Guidelines Version 2, 2021 for AML.
Is currently participating in a study of an investigational agent or using an investigational device.
Has undergone major surgery within 30 days of Study Day 1.
Has a known additional malignancy that is progressing or requires systemic treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
Previous allogeneic hematopoietic stem cell transplant (allo-HSCT) .
Prior treatment with any anti-CD47 or anti-SIRPα (signal regulatory protein alpha) agent.
Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of this subject to participate, in the opinion of the treating investigator.
Has received a live virus vaccine within 30 days of the planned first dose of study therapy.
Is pregnant, breastfeeding, or expecting to conceive or father a child within the projected duration of the study including 120 days following the last dose of study treatment.
Patient with known allergy or hypersensitivity to AK117, azacitidine or any of their components.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Weifeng Song, PhD
Phone
+86(0760)89873999
Email
clinicaltrials@akesobio.com
Facility Information:
Facility Name
The First Affiliated Hospital，Zhejiang University School of Medicine
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jie Jin, MD
Phone
0571-87236114
Email
jiej0503@163.com
12. IPD Sharing Statement
Learn more about this trial
A Trial of AK117 (Anti-CD47 Antibody) in Patients With Acute Myeloid Leukemia
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