Back to resultsIL3 CAR-T Cell Therapy for Patients With CD123 Positive Relapsed and/or Refractory Acute Myeloid Leukemia
Primary Purpose
Acute Myeloid Leukemia
Status
Not yet recruiting
Phase
Early Phase 1
Locations
China
Study Type
Interventional
Intervention
IL3 CAR T-cells
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring Acute Myeloid Leukemia, CAR T-cell therapy, CD123
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed diagnosis of CD123+ AML per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Myeloid Leukemia (2016.v1);
Relapsed or refractory CD123+ AML (meeting one of the following conditions):
- CR not achieved after standardized chemotherapy;
- CR achieved following the first induction, but CR duration is less than 12 months;
- Ineffectively after first or multiple remedial treatments;
- 2 or more relapses;
- The number of primordial cells in bone marrow is > 5% (by morphology), and/or > 0.01% (by flowcytometry);
- Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit ofnormal, creatinine ≤ 176.8 umol/L;
- Echocardiogram shows left ventricular ejection fraction (LVEF) ≥50%;
- No active infection in the lungs, blood oxygen saturation in indoorair is ≥ 92%;
- Estimated survival time ≥ 3 months;
- ECOG performance status 0 to 2;
- Patients or their legal guardians volunteer to participate in the studyand sign the informed consent.
Exclusion Criteria:
Subjects with any of the following exclusion criteria were not eligible for this trial:
- History of craniocerebral trauma, conscious disturbance,epilepsy,cerebrovascular ischemia, and cerebrovascular, hemorrhagicdiseases;
- Electrocardiogram shows prolonged QT interval, severe heart diseasessuch as severe arrhythmia in the past;
- Pregnant (or lactating) women;
- Patients with severe active infections (excluding simple urinarytractinfectionand bacterial pharyngitis);
- Active infection of hepatitis B virus or hepatitis C virus;
- Concurrent therapy with systemic steroids within 2 weeks prior toscreening, except for the patients recently or currently receiving in haledsteroids;
- Previously treated with any CAR-T cell product or other genetically-modified T cell therapies;
- Creatinine>2.5mg/dl, or ALT / AST > 3 times of normal amounts, or bilirubin>2.0 mg/dl;
- Other uncontrolled diseases that were not suitable for this trial;
- Patients with HIV infection;
- Any situations that the investigator believes may increase the risk ofpatients or interfere with the results of study.
Sites / Locations
- The First Affiliated Hospital，College of Medicine, Zhejiang University
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Administration of IL3 CAR T-cells
Arm Description
Outcomes
Primary Outcome Measures
Dose-limiting toxicity (DLT)
Adverse events assessed according to NCI-CTCAE v5.0 criteria
Incidence of treatment-emergent adverse events (TEAEs)
Incidence of treatment-emergent adverse events [Safety and Tolerability]
Secondary Outcome Measures
Acute Myeloid Leukemia (AML), Overall response rate (ORR)
Assessment of ORR (ORR = CR + CRi) at Month 6, 12, 18 and 24
AML, Overall survival (OS)
From the first infusion of IL3 CAR-T cells to death or the last visit
AML, Event-free survival (EFS)
From the first infusion of IL3 CAR-T cells to the occurrence of any event, including death, relapse or generelapse, disease progression (any one occurs first), and the last visit
Quality of life
Assessment using European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) scale [For item1-28: max score: 112, min score: 28, higher scores mean a better outcome; for item 28-29: max score: 14, min score: 2, higher scores mean a worse outcome] to measure Quality of life at Baseline, Month 1, 3, 6, 9 and 12
Activities of Daily Living (ADL) score
Assessment using Activities of Daily Living (ADL) scale (Barthel Index) [max score: 100, min score: 0, higher scores mean a better outcome] at Baseline, Month 1, 3, 6, 9 and 12
Instrumental Activities of Daily Living (IADL) score
Assessment of Instrumental Activities of Daily Living (IADL) scale [max score: 56, min score: 14, higher scores mean a worse outcome] at Baseline, Month 1, 3, 6, 9 and 12
Hospital Anxiety and Depression Scale (HADS) score
Assessment using Hospital Anxiety and Depression Scale (HADS) [max score: 42, min score: 0, higher scores mean a worse outcome] at Baseline, Month 1, 3, 6, 9 and 12
Full Information
NCT ID
NCT04599543
First Posted
October 21, 2020
Last Updated
October 22, 2020
Sponsor
Zhejiang University
Collaborators
Yake Biotechnology Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT04599543
Brief Title
IL3 CAR-T Cell Therapy for Patients With CD123 Positive Relapsed and/or Refractory Acute Myeloid Leukemia
Official Title
Clinical Trial for the Safety and Efficacy of IL3 CAR-T Cell Therapy for Patients With CD123 Positive Relapsed and/or Refractory Acute Myeloid Leukemia
Study Type
Interventional
2. Study Status
Record Verification Date
October 2020
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 15, 2020 (Anticipated)
Primary Completion Date
November 15, 2023 (Anticipated)
Study Completion Date
November 15, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Zhejiang University
Collaborators
Yake Biotechnology Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
A Study of IL3 CAR-T Cell Therapy for Patients With CD123 Positive Relapsed and/or Refractory Acute Myeloid Leukemia.
Detailed Description
This is a single arm, open-label, single-center study. This study is indicated for relapsed or refractory CD123+ acute myeloid leukemia. The selections of dose levels and the number of subjects are based on clinical trials of similar foreign products. 36 patients will be enrolled. Primary objective is to explore the safety, main consideration is dose-related safety.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia
Keywords
Acute Myeloid Leukemia, CAR T-cell therapy, CD123
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
36 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Administration of IL3 CAR T-cells
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
IL3 CAR T-cells
Other Intervention Name(s)
IL3 CAR-T cells injection
Intervention Description
Each subject receive IL3 CAR T-cells by intravenous infusion
Primary Outcome Measure Information:
Title
Dose-limiting toxicity (DLT)
Description
Adverse events assessed according to NCI-CTCAE v5.0 criteria
Time Frame
Baseline up to 28 days after IL3 targeted CAR T-cells infusion
Title
Incidence of treatment-emergent adverse events (TEAEs)
Description
Incidence of treatment-emergent adverse events [Safety and Tolerability]
Time Frame
Up to 2 years after IL3 targeted CAR T-cells infusion
Secondary Outcome Measure Information:
Title
Acute Myeloid Leukemia (AML), Overall response rate (ORR)
Description
Assessment of ORR (ORR = CR + CRi) at Month 6, 12, 18 and 24
Time Frame
At Month 1, 3, 6, 12, 18 and 24
Title
AML, Overall survival (OS)
Description
From the first infusion of IL3 CAR-T cells to death or the last visit
Time Frame
Up to 2 years after IL3 CAR-T cells infusion
Title
AML, Event-free survival (EFS)
Description
From the first infusion of IL3 CAR-T cells to the occurrence of any event, including death, relapse or generelapse, disease progression (any one occurs first), and the last visit
Time Frame
Up to 2 years after IL3 CAR-T cells infusion
Title
Quality of life
Description
Assessment using European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) scale [For item1-28: max score: 112, min score: 28, higher scores mean a better outcome; for item 28-29: max score: 14, min score: 2, higher scores mean a worse outcome] to measure Quality of life at Baseline, Month 1, 3, 6, 9 and 12
Time Frame
At Baseline, Month 1, 3, 6, 9 and 12
Title
Activities of Daily Living (ADL) score
Description
Assessment using Activities of Daily Living (ADL) scale (Barthel Index) [max score: 100, min score: 0, higher scores mean a better outcome] at Baseline, Month 1, 3, 6, 9 and 12
Time Frame
At Baseline, Month 1, 3, 6, 9 and 12
Title
Instrumental Activities of Daily Living (IADL) score
Description
Assessment of Instrumental Activities of Daily Living (IADL) scale [max score: 56, min score: 14, higher scores mean a worse outcome] at Baseline, Month 1, 3, 6, 9 and 12
Time Frame
At Baseline, Month 1, 3, 6, 9 and 12
Title
Hospital Anxiety and Depression Scale (HADS) score
Description
Assessment using Hospital Anxiety and Depression Scale (HADS) [max score: 42, min score: 0, higher scores mean a worse outcome] at Baseline, Month 1, 3, 6, 9 and 12
Time Frame
At Baseline, Month 1, 3, 6, 9 and 12
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed diagnosis of CD123+ AML per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Myeloid Leukemia (2016.v1);
Relapsed or refractory CD123+ AML (meeting one of the following conditions):
CR not achieved after standardized chemotherapy;
CR achieved following the first induction, but CR duration is less than 12 months;
Ineffectively after first or multiple remedial treatments;
2 or more relapses;
The number of primordial cells in bone marrow is > 5% (by morphology), and/or > 0.01% (by flowcytometry);
Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit ofnormal, creatinine ≤ 176.8 umol/L;
Echocardiogram shows left ventricular ejection fraction (LVEF) ≥50%;
No active infection in the lungs, blood oxygen saturation in indoorair is ≥ 92%;
Estimated survival time ≥ 3 months;
ECOG performance status 0 to 2;
Patients or their legal guardians volunteer to participate in the studyand sign the informed consent.
Exclusion Criteria:
Subjects with any of the following exclusion criteria were not eligible for this trial:
History of craniocerebral trauma, conscious disturbance,epilepsy,cerebrovascular ischemia, and cerebrovascular, hemorrhagicdiseases;
Electrocardiogram shows prolonged QT interval, severe heart diseasessuch as severe arrhythmia in the past;
Pregnant (or lactating) women;
Patients with severe active infections (excluding simple urinarytractinfectionand bacterial pharyngitis);
Active infection of hepatitis B virus or hepatitis C virus;
Concurrent therapy with systemic steroids within 2 weeks prior toscreening, except for the patients recently or currently receiving in haledsteroids;
Previously treated with any CAR-T cell product or other genetically-modified T cell therapies;
Creatinine>2.5mg/dl, or ALT / AST > 3 times of normal amounts, or bilirubin>2.0 mg/dl;
Other uncontrolled diseases that were not suitable for this trial;
Patients with HIV infection;
Any situations that the investigator believes may increase the risk ofpatients or interfere with the results of study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
He Huang, PhD
Phone
86-13605714822
Email
hehuangyu@126.com
First Name & Middle Initial & Last Name or Official Title & Degree
Yongxian Hu, PhD
Phone
86-15957162012
Email
huyongxian2000@aliyun.com
Facility Information:
Facility Name
The First Affiliated Hospital，College of Medicine, Zhejiang University
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310003
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
He Huang, PhD
Phone
86-13605714822
Email
hehuangyu@126.com
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
IL3 CAR-T Cell Therapy for Patients With CD123 Positive Relapsed and/or Refractory Acute Myeloid Leukemia
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