NKG2D CAR-T Cell Therapy for Patients With Relapsed and/or Refractory Acute Myeloid Leukemia

Acute Myeloid Leukemia Clinical Trial

Official title:

Clinical Trial for the Safety and Efficacy of NKG2D CAR-T Cell Therapy for Patients With Relapsed and/or Refractory Acute Myeloid Leukemia

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04658004
• Other study ID #: NKG2D-001
• Status: Not yet recruiting
• Phase: Early Phase 1
• Start date: January 15, 2021
• Est. completion date: January 15, 2027

Study information

• Verified date: December 2020
• Source: Zhejiang University
• Contact: He Huang, PhD
• Phone: 86-13605714822
• Email: hehuangyu[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A Study of NKG2D CAR-T Cell Therapy for Patients With Relapsed and/or Refractory Acute Myeloid Leukemia.

Description:

This is a single arm, open-label, single-center study. This study is indicated for relapsed or refractory NKG2D ligand positive 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 36
• Est. completion date: January 15, 2027
• Est. primary completion date: January 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Histologically confirmed diagnosis of NKG2D ligand positive AML per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Myeloid Leukemia (2016.v1);

2. Relapsed or refractory NKG2D ligand positive 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 flow cyto metry);

4. Total bilirubin = 51 umol/L, ALT and AST = 3 times of upper limit of normal, 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 indoor air 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 study and 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, hemorrhagic diseases;

2. Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;

3. Pregnant (or lactating) women;

4. Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis);

5. Active infection of hepatitis B virus or hepatitis C virus;

6. Concurrent therapy with systemic steroids within 2 weeks prior to screening, except for the patients recently or currently receiving in haled steroids;

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 of patients or interfere with the results of study.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• NKG2D CAR T-cells
Each subject receive NKG2D CAR T-cells by intravenous infusion

Locations

Country	Name	City	State
China	The First Affiliated Hospital,College of Medicine, Zhejiang University	Hangzhou	Zhejiang

Sponsors (2)

Lead Sponsor	Collaborator
Zhejiang University	Yake Biotechnology Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicity (DLT)	Adverse events assessed according to NCI-CTCAE v5.0 criteria	Baseline up to 28 days after NKG2D targeted CAR T-cells infusion
Primary	Incidence of treatment-emergent adverse events (TEAEs)	Incidence of treatment-emergent adverse events [Safety and Tolerability]	Up to 2 years after NKG2D targeted CAR T-cells infusion
Secondary	Acute Myeloid Leukemia (AML), Overall response rate (ORR)	Assessment of ORR (ORR = CR + CRi) at Month 1, 3, 6, 12, 18 and 24	At Month 1, 3, 6, 12, 18 and 24
Secondary	AML, Overall survival (OS)	. AML, Overall survival (OS) From the first infusion of NKG2D CAR-T cells to death or the last visit	Up to 2 years after NKG2D CAR-T cells infusion
Secondary	AML, Event-free survival (EFS)	From the first infusion of NKG2D CAR-T cells to the occurrence of any event, including death, relapse or gene relapse disease progression (any one occurs first), and the last visit	Up to 2 years after NKG2D CAR-T cells infusion
Secondary	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	:At Baseline, Month 1, 3, 6, 9 and 12
Secondary	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	At Baseline, Month 1, 3, 6, 9 and 12
Secondary	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	At Baseline, Month 1, 3, 6, 9 and 12
Secondary	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	At Baseline, Month 1, 3, 6, 9 and 12