Clinical trial NCT04658004: NKG2D CAR-T Cell Therapy for Patients With Relapsed and/or Refractory Acute Myeloid Leukemia
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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: EARLY_PHASE1
Conditions: Acute Myeloid Leukemia
Keywords: Acute Myeloid Leukemia
CAR T-cell therapy
NKG2D
Lead sponsor: Zhejiang University
Sponsor class: OTHER
Collaborators: name: Yake Biotechnology Ltd.
First posted: 2020-12-08
Enrollment: 36
Sex: ALL
Minimum age (years): 3
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A Study of NKG2D CAR-T Cell Therapy for Patients With 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 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Dose-limiting toxicity (DLT)
timeFrame: Baseline up to 28 days after NKG2D targeted CAR T-cells infusion
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 2 years after NKG2D targeted CAR T-cells infusion
Secondary outcomes:
measure: Acute Myeloid Leukemia (AML), Overall response rate (ORR)
timeFrame: At Month 1, 3, 6, 12, 18 and 24
measure: AML, Overall survival (OS)
timeFrame: Up to 2 years after NKG2D CAR-T cells infusion
measure: AML, Event-free survival (EFS)
timeFrame: Up to 2 years after NKG2D CAR-T cells infusion
measure: Quality of life
timeFrame: :At Baseline, Month 1, 3, 6, 9 and 12
measure: Activities of Daily Living (ADL) score
timeFrame: At Baseline, Month 1, 3, 6, 9 and 12
measure: Instrumental Activities of Daily Living (IADL) score
timeFrame: At Baseline, Month 1, 3, 6, 9 and 12
measure: Hospital Anxiety and Depression Scale (HADS) score
timeFrame: At Baseline, Month 1, 3, 6, 9 and 12
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The First Affiliated Hospital，College of Medicine, Zhejiang University
state: Zhejiang
Study officials:
References: