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

Early Phase 1

Not yet recruiting

• Conditions: Hematological Malignancies
• Interventions: Drug: NK cells/Combined Monoclonal Antibodies

• Registration Number: NCT04662788
• Lead Sponsor: Zhejiang University

Brief Summary

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

Detailed Description

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.

Study Timeline

• Status Verified: 2020-12
• Study First Submitted: 2020-12-08
• Study First Submitted QC: 2020-12-08
• Last Update Submitted: 2020-12-08
• Study First Posted: 2020-12-10
• Last Update Posted: 2020-12-10
• Study Start: 2021-01-01
• Primary Completion: 2024-01-01
• Study Completion: 2027-01-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

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

2. Relapsed or refractory 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

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Administration of NK cells/Combined Monoclonal Antibodies	NK cells/Combined Monoclonal Antibodies	-

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Acute Myeloid Leukemia (AML), Overall response rate (ORR)	At Month 1, 3, 6, 12, 18 and 24	Assessment of ORR (ORR = CR + CRi) at Month 6, 12, 18 and 24
AML, Overall survival (OS)	Up to 2 years after NK cells infusion	From the first infusion of NK cells/Combined Monoclonal Antibodies to death or the last visit
AML, Event-free survival (EFS)	Up to 2 years after NK cell/ Combined Monoclonal Antibodies infusion	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
Hospital Anxiety and Depression Scale (HADS) score	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
Quality of life	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
Activities of Daily Living (ADL) score	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
Instrumental Activities of Daily Living (IADL) score	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

Trial Locations

Locations (1)

The First Affiliated Hospital, College of Medicine, Zhejiang University; 🇨🇳 Hangzhou, Zhejiang, China