IL3 CAR-T Cell Therapy for Patients With CD123 Positive Relapsed and/or Refractory Acute Myeloid Leukemia

• ClinicalTrials.gov Identifier: NCT04599543
• Recruitment Status: Not yet recruiting
• First Posted: October 22, 2020
• Last Update Posted: October 27, 2020
• Sponsor: Zhejiang University
• Collaborator: Yake Biotechnology Ltd.
• Information provided by (Responsible Party): He Huang, Zhejiang University

Study Description

Brief Summary:

A Study of IL3 CAR-T Cell Therapy for Patients With CD123 Positive Relapsed and/or Refractory Acute Myeloid Leukemia.

Condition or disease	Intervention/treatment	Phase
Acute Myeloid Leukemia	Drug: IL3 CAR T-cells	Early Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Estimated Study Start Date: November 15, 2020
• Estimated Primary Completion Date: November 15, 2023
• Estimated Study Completion Date: November 15, 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Administration of IL3 CAR T-cells	Drug: IL3 CAR T-cells; Each subject receive IL3 CAR T-cells by intravenous infusion; Other Name: IL3 CAR-T cells injection

Outcome Measures

Primary Outcome Measures :

1. Dose-limiting toxicity (DLT) [ Time Frame: Baseline up to 28 days after IL3 targeted CAR T-cells infusion ]
   Adverse events assessed according to NCI-CTCAE v5.0 criteria
2. Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 2 years after IL3 targeted CAR T-cells infusion ]
   Incidence of treatment-emergent adverse events [Safety and Tolerability]

Secondary Outcome Measures :

1. Acute Myeloid Leukemia (AML), Overall response rate (ORR) [ Time Frame: At Month 1, 3, 6, 12, 18 and 24 ]
   Assessment of ORR (ORR = CR + CRi) at Month 6, 12, 18 and 24
2. AML, Overall survival (OS) [ Time Frame: Up to 2 years after IL3 CAR-T cells infusion ]
   From the first infusion of IL3 CAR-T cells to death or the last visit
3. AML, Event-free survival (EFS) [ Time Frame: Up to 2 years after IL3 CAR-T cells infusion ]
   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
4. Quality of life [ Time Frame: At Baseline, Month 1, 3, 6, 9 and 12 ]
   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
5. Activities of Daily Living (ADL) score [ Time Frame: At Baseline, Month 1, 3, 6, 9 and 12 ]
   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
6. Instrumental Activities of Daily Living (IADL) score [ Time Frame: At Baseline, Month 1, 3, 6, 9 and 12 ]
   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
7. Hospital Anxiety and Depression Scale (HADS) score [ Time Frame: At Baseline, Month 1, 3, 6, 9 and 12 ]
   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

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Histologically confirmed diagnosis of CD123+ AML per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Myeloid Leukemia (2016.v1);

2. Relapsed or refractory CD123+ AML (meeting one of the following conditions):

   1. CR not achieved after standardized chemotherapy;
   2. CR achieved following the first induction, but CR duration is less than 12 months;
   3. Ineffectively after first or multiple remedial treatments;
   4. 2 or more relapses;
3. The number of primordial cells in bone marrow is > 5% (by morphology), and/or > 0.01% (by flowcytometry);
4. Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit ofnormal, creatinine ≤ 176.8 umol/L;
5. Echocardiogram shows left ventricular ejection fraction (LVEF) ≥50%;
6. No active infection in the lungs, blood oxygen saturation in indoorair is ≥ 92%;
7. Estimated survival time ≥ 3 months;
8. ECOG performance status 0 to 2;
9. 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:

1. History of craniocerebral trauma, conscious disturbance,epilepsy,cerebrovascular ischemia, and cerebrovascular, hemorrhagicdiseases;
2. Electrocardiogram shows prolonged QT interval, severe heart diseasessuch as severe arrhythmia in the past;
3. Pregnant (or lactating) women;
4. Patients with severe active infections (excluding simple urinarytractinfectionand bacterial pharyngitis);
5. Active infection of hepatitis B virus or hepatitis C virus;
6. Concurrent therapy with systemic steroids within 2 weeks prior toscreening, except for the patients recently or currently receiving in haledsteroids;
7. Previously treated with any CAR-T cell product or other genetically-modified T cell therapies;
8. Creatinine>2.5mg/dl, or ALT / AST > 3 times of normal amounts, or bilirubin>2.0 mg/dl;
9. Other uncontrolled diseases that were not suitable for this trial;
10. Patients with HIV infection;
11. Any situations that the investigator believes may increase the risk ofpatients or interfere with the results of study.

Contacts and Locations

Contacts

Contact: He Huang, PhD; 86-13605714822; hehuangyu@126.com

Contact: Yongxian Hu, PhD; 86-15957162012; huyongxian2000@aliyun.com

Locations

China, Zhejiang

The First Affiliated Hospital，College of Medicine, Zhejiang University

Hangzhou, Zhejiang, China, 310003

Contact: He Huang, PhD 86-13605714822 hehuangyu@126.com

Sponsors and Collaborators

Zhejiang University

Yake Biotechnology Ltd.

More Information

• Responsible Party: He Huang, Clinical Professor, Zhejiang University
• ClinicalTrials.gov Identifier: NCT04599543
• Other Study ID Numbers: CD123-001
• First Posted: October 22, 2020
• Last Update Posted: October 27, 2020
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by He Huang, Zhejiang University:

Acute Myeloid Leukemia; CAR T-cell therapy; CD123

Additional relevant MeSH terms:

Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Neoplasms by Histologic Type; Neoplasms