Clinical Study on the Safety and Effectiveness of NK Cells/Combined Monoclonal Antibodies in the Treatment of Hematological Malignancies

Study Overview
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Brief Summary
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Clinical study on the safety and effectiveness of NK cells/combined monoclonal antibodies in the treatment of hematological malignancies

Detailed Description
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This is a single arm, open-label, single-center study. This study is indicated for hematological malignancies. 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.

Official Title
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Clinical Trial for the Safety and Effectiveness of NK Cells/Combined Monoclonal Antibodies in the Treatment of Hematological Malignancies

Conditions
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Hematological Malignancies

Intervention / Treatment
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* Drug: NK cells/Combined Monoclonal Antibodies


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of AML per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Myeloid Leukemia (2016.v1); Relapsed or refractory 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: 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.

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Administration of NK cells/Combined Monoclonal Antibodies<br> | Drug: NK cells/Combined Monoclonal Antibodies<br>* Each subject receive NK cells/Combined Monoclonal Antibodies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity (DLT) | Adverse events assessed according to NCI-CTCAE v5.0 criteria | Baseline up to 28 days after NK cells/Combined Monoclonal Antibodies infusion | 
| Incidence of treatment-emergent adverse events (TEAEs) | Incidence of treatment-emergent adverse events [Safety and Tolerability] | Up to 2 years after NK cells/Combined Monoclonal Antibodies infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute Myeloid Leukemia (AML), Overall response rate (ORR) | Assessment of ORR (ORR = CR + CRi) at Month 6, 12, 18 and 24 | At Month 1, 3, 6, 12, 18 and 24 | 
| AML, Overall survival (OS) | From the first infusion of NK cells/Combined Monoclonal Antibodies to death or the last visit | Up to 2 years after NK cells infusion | 
| AML, Event-free survival (EFS) | From the first infusion of NK cells/Combined Monoclonal Antibodies to the occurrence of any event, including death, relapse or generelapse, disease progression (any one occurs first), and the last visit | Up to 2 years after NK cell/ Combined Monoclonal Antibodies infusion | 
| 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 | 
| 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 | 
| 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 | 
| 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 |